TW510900B

TW510900B - Benzothiophenes, benzofurans, and indoles useful in the treatment of insulin resistance and hyperglycemia

Info

Publication number: TW510900B
Application number: TW088107532A
Authority: TW
Inventors: Jay E Wrobel; Arlene J Dietrich; Madelene M Antane
Original assignee: Wyeth Corp
Priority date: 1998-05-12
Filing date: 1999-05-10
Publication date: 2002-11-21
Also published as: JP2002516321A; SK16992000A3; ID26244A; ZA200005961B; AU3893999A; HUP0101792A3; CA2330620A1; PL344081A1; EE200000653A; AR015294A1; TR200003333T2; BR9911779A; EP1077969A1; BG104918A; HRP20000767A2; CN1308626A; NO20005677D0; EA200001175A1; HUP0101792A2; AU756337B2

Abstract

This invention provides compounds of formula I having the structure wherein Ar is formula; A is hydrogen; B and D are each independently hydrogen, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, nitro, amino or -NR1CO2R1a; R1a is hydrogen, or alkyl of 1-6 carbon atoms; R1 is hydrogen, alkyl of 1-6 carbon atoms or -CH2CO2R1; R1 is hydrogen or alkyl of 1-6 carbon atoms; E is S or O; X is hydrogen, halogen, alkyl of 1-6 carbon atoms or phenylsulfonyl; Y is hydrogen, halogen, alkyl of 1-6 carbon atoms, NR3R3a; R3 and R3a are each independently hydrogen or alkyl of 1-6 carbon atoms; C is hydrogen or OR4; R4 is hydrogen, alkyl of 1-6 carbon atoms or -CH(R5)W; R5 is hydrogen, alkyl of 1-6 carbon atoms or phenylalkyl of 1-6 carbon atoms in the alkyl moiety; W is CO2R6 wherein R6 is hydrogen, alkyl of 1-6 carbon atoms or phenyl; or W is -CONR6bCHR7bCO2R6, wherein R6b, R7b, R6 are hydrogen, alkyl of 1-6 carbon atoms or phenyl; Z1 and Z2 may be taken together as a diene unit having the formula -CH=CH-CH=CH or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.

Description

明00 經濟部智慧財產局員工消費合作社印制农 A7 B7 五'發明說明（f ) 背暑己知葡萄糖無抗性病患常具抗胰島素性。Reaven等人 (American Journal of Medicine 1976, 60, 80)使用持續灌入葡萄糖及胰島素（胰島素/葡萄糖固定技術）及口》萄糖抗性試驗以蘭示抗胰島素性存於廣泛非肥胖，非酮病病患中。此病患由具臨界葡萄糖抗性至明顯斷食高血糖性。此研究中糖尿病病患含胰島素相鬪（IDDM) 及非胰島素相關（N I D D Μ )病患。與實質抗胰島素性相關者為更易測量之高血糖症，其可由精確測量病患血漿中循環血漿胰島素濃度而定。高血糖症可因抗胰島素性而存在，如於肥胖及/或糖尿病病患（NIDDM)及/或®萄糖無抗性病患，或IDDM病患中，因注射過量（較正常生理内分泌腺分泌之激素）胰島素而引起。高血糖症與肥胖及大血管絶血症（如動脈粥瘤硬化）之關連已由數個實驗，臨床及流行病學研究而確定（由 Stout, Metabolism 1985, 34, 7綜逑，且由 Pyorala等人，Diabetes/ Metabolisiti Reviews 1 9 8 7, 3 , 4 6 3# 逑）。由口投予以葡萄糖後1及2小時會明顯提升血漿胰島素濃度，因而增加冠狀心臟病之危險。由於多數研究皆不含糖尿病病患，動脈粥瘤硬化危險性與糖尿病之相關數據不夠眾多，但對非糖尿病病患皆指向同一方向（Pyorala等人）。然而，糖尿病病患中因動脈粥瘤硬化之死亡率超過非糖尿病族群（Pyorala 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂--------- (請先閱讀背面之注意事項再填寫本頁) 510900 A7 _B7_ 五、發明說明（> ) 等人;J a r r e 11 Diabetes/Metabolisra Reviews 1989， 5， 547; Harris等人，Mortality from diabetes, in (請先閱讀背面之注意事項再填寫本頁)Ming 00 Printed by the Consumers 'Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 Five' invention description (f) Back to the heat It is known that glucose-resistant patients often have insulin resistance. Reaven et al. (American Journal of Medicine 1976, 60, 80) used continuous glucose and insulin (insulin / glucose fixation technology) and oral glucose resistance tests to show that insulin resistance exists in a wide range of non-obese, non-keto In sick patients. The patient went from having critical glucose resistance to being markedly fasting to hyperglycemia. Diabetic patients in this study included insulin-dependent diarrhea (IDDM) and non-insulin-related (N ID D DM) patients. Related to parenchymal insulin resistance is more easily measured hyperglycemia, which can be determined by accurate measurement of circulating plasma insulin concentrations in the patient's plasma. Hyperglycemia may be due to insulin resistance, such as in obese and / or diabetic patients (NIDDM) and / or glucose-resistant patients, or IDDM patients, due to excessive injection (more normal physiological endocrine glands) Secreted hormone) caused by insulin. The association of hyperglycemia with obesity and macrovascular hemorrhage (such as atherosclerosis) has been determined by several experimental, clinical, and epidemiological studies (by Stout, Metabolism 1985, 34, 7, and by Pyorala Et al., Diabetes / Metabolisiti Reviews 1 9 8 7, 3, 4 6 3 # 逑). Glucose 1 and 2 hours after oral administration will significantly increase plasma insulin concentration, thereby increasing the risk of coronary heart disease. Since most studies do not include diabetic patients, there are insufficient data on the risk of atherosclerosis and diabetes, but they point in the same direction for non-diabetic patients (Pyorala et al.). However, the mortality rate due to atherosclerosis in diabetic patients exceeds that of non-diabetic populations (Pyorala paper size applies Chinese National Standard (CNS) A4 specification (210 X 297 mm)) ----------- --------- Order --------- (Please read the notes on the back before filling out this page) 510900 A7 _B7_ V. Description of the Invention (>) et al; J arre 11 Diabetes / Metabolisra Reviews 1989, 5, 547; Harris et al., Mortality from diabetes, in (Please read the notes on the back before filling out this page)

Diabtes in America 1985) 〇動脈粥瘤硬化之各別肥胖及高血壓危險因子伴隨以胰島素抗性。使用胰島素/葡萄糖固定技術，追蹤葡萄糖洋入及間接卡路里計，已顯示高血壓之胰島素抗性位於固圍組織（主為肌肉）及直接與高血壓駸重性相關（Defronzo and Ferrannini , Diabetes Care, 1991， 14， 17 3) 〇於肥胖症之高血壓，胰島素抗性會造成高胰島素症，其由生熱而作為限制體重增加之機制，但胰島素亦增加緊鈉再吸收，而剌激緊，心及血管分布之交感神經条而造成高血壓。經濟部智慧財產局員工消費合作社印製目前已知抗胰島素症常為胰島素受器訊號条異常所致 ,即胰島素結合至受器後之部位。累積科學證據顯示主要組織對胰島素之抗胰島素性（肌肉，肝，脂肪），強烈顯示在於急速反應中早期胰島素訊號傳遞基之異常，特於胰島素受器激酶活性會消失（由1^1^1^，〇1^0181(^“ 1991，34，8 4 8綜述）。蛋白質-酪胺酸磷酸酶（PTP酶）於調整蛋白質磷酸化扮演重要角色。胰島素與其受器之作用會造成受器蛋白質中特定酪胺酸分子磷酸化，因而活化受器激酶。P T P酶對活化胰島素受器去磷酸化，而改變酪胺酸激酶活性。本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印製〉10900 A7 ----^- 五、發明說明（》） PTP酶亦可調節受器後之訊號，係由催化胰島素受器激酶分子受質之去磷酸化而達成。此酶極可能與胰島素受器密切相_，因而最可能調整胰島素受器激酶活性，含 PTP1B， LAR力 ΡΤΡα 及 SH-TPT2(B， J, Goldstein· J· Cellular Biochemistry 1992, 48, 33, B. J. Goldstein ，Receptor 1993, 3，1-15; F . Ahmad and B. J·Diabtes in America 1985) 〇 Individual obesity and hypertension risk factors for atherosclerosis are accompanied by insulin resistance. Using insulin / glucose fixation technology to track glucose influx and indirect calorimeters, it has been shown that insulin resistance in hypertension is located in the surrounding tissue (mainly muscle) and is directly related to the severity of hypertension (Defronzo and Ferrannini, Diabetes Care, 1991, 14, 17 3) In high blood pressure of obesity, insulin resistance can cause hyperinsulinism, which is a mechanism for limiting weight gain by generating heat, but insulin also increases tight sodium reabsorption, and irritates, Cardiac and vascular distribution of sympathetic nerve strips cause hypertension. Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. It is currently known that insulin resistance is often caused by an abnormality in the signal line of the insulin receptor, that is, where the insulin is bound to the receptor. Cumulative scientific evidence shows that insulin resistance (muscle, liver, fat) of major tissues to insulin is strongly shown to be due to the abnormality of the early insulin signal transmission base in the rapid response, and the insulin receptor kinase activity will disappear (from 1 ^ 1 ^ 1 ^, 〇1 ^ 0181 (^ "1991, 34, 8 4 8 review). Protein-tyrosine phosphatase (PTPase) plays an important role in regulating protein phosphorylation. The effect of insulin and its receptor will cause receptor protein Specific tyrosine molecules are phosphorylated in the medium, thereby activating receptor kinases. PTP enzymes dephosphorylate activated insulin receptors and change tyrosine kinase activity. This paper is sized to the Chinese National Standard (CNS) A4 (210 X 297) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs> 10900 A7 ---- ^-V. Description of the invention (") PTP enzyme can also regulate the signal after the receptor, which is mediated by the catalytic insulin receptor kinase molecule It is achieved by dephosphorylation. This enzyme is very likely to be closely related to the insulin receptor_, so it is most likely to regulate the insulin receptor kinase activity, including PTP1B, LAR, TPTPα and SH-TPT2 (B, J, G oldstein · J · Cellular Biochemistry 1992, 48, 33, B. J. Goldstein, Receptor 1993, 3, 1-15; F. Ahmad and B. J ·

Goldstein Biochem Biophys Acta 1995, 1248, 57-69)〇Goldstein Biochem Biophys Acta 1995, 1248, 57-69).

McGuire 等人（Diabetes 1991，40，9 3 9 )發現非糖尿病葡萄糖不抗性病患相對於正常人，於肌肉組織中P T P酶活性顯著上升，且胰島素灌入無法如對胰島素過敏病患抑制PTP酶活性。McGuire et al. (Diabetes 1991, 40, 9 3 9) found that patients with non-diabetic glucose intolerance have significantly increased PTPase activity in muscle tissues compared to normal subjects, and that insulin infusion cannot inhibit PTP as in insulin allergic patients Enzyme activity.

Meyerovitch等人（J· Clinical Invest. 1989， 84， 978)於2個IDDM鼠模型中（遣傳糖尿病BB鼠及STZ引發糖尿病鼠），其肝有顯著上升之ρτρ酶活性。Serdy等人（ Metabolism，44，1 0 7 4，1 9 9 5 )觀察得於肥胖，糖尿病 (ob/ob鼠（NIDDM之遣傳鼠模型 >，其肝有相似之PTP酶活性上升。本發明化合物顯示可活體外抑制鼠肝徼小鼠及人重組 ΡΤΡ酶- lB(hPTP-lB)之ΡΡ酶。其可用以治療肥胖症，葡萄糖不抗性，糖尿病，大及小血管之高血壓及絶血性言所伴隨之抗胰島素性。本紙張尺度適用中國國家標準（CNS)A4規格（210 x 297公釐） --------------------訂--------- (請先閱讀背面之注音？事項再填寫本頁) 510900 A7 B7 五、發明說明（4 )Meyerovitch et al. (J. Clinical Invest. 1989, 84, 978) in two IDDM mouse models (removal of diabetic BB mice and STZ-induced diabetic mice) had significantly increased liver ρτρ enzyme activity. Serdy et al. (Metabolism, 44, 107, 995) observed obesity, diabetes (ob / ob mice (NIDDM's rat model)>, and their liver had similar PTPase activity increase. The compounds of the invention have been shown to inhibit in vitro the liver enzymes of mouse and human recombinant PTPase-lB (hPTP-lB). It can be used to treat obesity, glucose intolerance, diabetes, hypertension in large and small blood vessels, and The insulin resistance accompanied by the hemorrhagic nature. This paper size applies the Chinese National Standard (CNS) A4 (210 x 297 mm) -------------------- Order --------- (Please read the note on the back? Matters before filling out this page) 510900 A7 B7 V. Description of the invention (4)

本化合物在試管内抑制從鼠肝徼粒體誘導之PTP酶及人重組PTP酶（hPTP-lB)，可用以治療隨伴肥胖之抗胰島素症，不耐糖症，糖尿病，高血壓及大小血管之絶血症 B.Reidl，等（EP 693491A1)掲示當作抗菌劑之Bf唑啶酮AThis compound inhibits PTPase and human recombinant PTPase (hPTP-lB) induced from rat hepatocytes and granules in a test tube. B. Reidl, et.

NHAcNHAc

AA

A.Bridges，等（EP 568289A2)掲示當作尿激酶抑制劑之瞎盼硫苯脒B hA. Bridges, et al. (EP 568289A2) suggest thiophene as a urokinase inhibitor B h

H2NH2N

B Η . - Μ . Chen, e t al.,Indian J . Chein. ,Sect. B : 0 r g. C h e m. Include. Med. C h e m. 1 9 9 6 , 35B(12) ,1304 -1 3 0 7掲示化合物C。本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製B Η.-Μ. Chen, et al., Indian J. Chein., Sect. B: 0 r g. C he m. Include. Med. C he m. 1 9 9 6, 35B (12), 1304- 1 3 0 7 shows compound C. This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) (Please read the precautions on the back before filling this page)

510900 A7 B7 五、發明說明（r)510900 A7 B7 V. Description of the invention (r)

(請先閱讀背面之注意事項再填寫本頁) N.R. Guirguis, e t a 1. , J. P r a k t . C h e a . 1 9 9 0,(Please read the notes on the back before filling this page) N.R. Guirguis, e t a 1., J. P r a k t. C h e a. 1 9 9 0,

3 3 2 ( 3 )，4 14-4 18掲示化合物D3 3 2 (3), 4 14-4 18 shows compound D

N.R· Guirguis, et al.,Liebigs Ann. Che®. 1986, 1003-1011 掲示苯駢 B塞盼 E. M. C.Dubroeucq et al·， (EP 248834A1)也掲示當作解焦慮劑之E (Ri =C〇2 H) 經濟部智慧財產局員工消費合作社印製NR Guirguis, et al., Liebigs Ann. Che®. 1986, 1003-1011, which shows that Benzene, B, and Semper EMCCDubroeucq et al. (EP 248834A1) also shows E as an anxiolytic agent (Ri = C〇2 H) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs

本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 510900

A7 _B7_五、發明說明（b ) T . Kuroda，e t a 1 . , J . 0 r g . C h e in . 1994， 5 9 , 7 3 5 3 - 7 3 5 7 and J. C h ei. S o c. ,C h e m . C o ffl m u n . 1991, 1635- 1 6 3 6掲示苯駢睹盼FA7 _B7_ V. Description of the invention (b) T. Kuroda, eta 1., J. 0 rg. C he in. 1994, 5 9, 7 3 5 3-7 3 5 7 and J. C h ei. S o c., C hem. Coffl mun. 1991, 1635- 1 6 3 6

F A.I.Hashem, J . P r a k t . Chera. 1 9 7 7 , 3 1 9，6 8 9 - 6 9 2 掲示苯駢呋喃GF A.I. Hashem, J. Prak. Chera. 1 9 7 7, 3 1 9, 6 8 9-6 9 2

---------------------訂---- (請先閱讀背面之注意事項再填寫本頁) S, 經濟部智慧財產局員工消費合作社印製 G Y· Akao，等日本特開平 JP 04016854 A2 (CA: 117: 3 6 5 7 0 )掲示含4-芳基-萘駢〔2,3-b〕瞎盼環条之6種化合物，傺該環条之環丁烯二基二聚物，當作光電圔光受體，其一範例呈如下構造Η -8 _ 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 B7 經濟部智慧財產局員工消費合作社印製--------------------- Order ---- (Please read the notes on the back before filling this page) GY Akao, et al., Japanese Patent Application Laid-Open No. JP 04016854 A2 (CA: 117: 3 6 5 7 0), showing 6 compounds containing 4-aryl-naphthalene [2,3-b] ring, The cyclobutene dimer of the ring strip is used as a photoelectric photoreceptor. An example is the following structure. -8 _ This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 510900 A7 B7 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs

VP 發明說明（7)VP invention description (7)

ΗΗ

J . Ρ . Konopelski , e t a 1 . , Synlett 1996，6 0 9 - 6 1 1 掲示吲Ιϊ朵IJ. Ρ. Konopelski, e t a 1., Synlett 1996, 609-6 1 1

P. Molina, e t a 1, Tetrahedron, 1 9 9 4， 50,5027-36 and Tetrahedron Lett.,1993, 34， 2809·2812掲示 B引時衍生物J -9 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) 510900 A7 B7 五、發明說明（P. Molina, eta 1, Tetrahedron, 1 9 9 4, 50, 5027-36 and Tetrahedron Lett., 1993, 34, 2809 · 2812 show B time derivative J -9-This paper is in accordance with the Chinese National Standard (CNS ) A4 size (210 X 297 mm) (Please read the notes on the back before filling out this page) 510900 A7 B7 V. Description of the invention (

R = H 或 MeR = H or Me

R k · Napolitano, e t al. ,Tetrahedron 1989， 45, 6 7 4 9 - 6 G掲示吲呤KHR k · Napolitano, e t al., Tetrahedron 1989, 45, 6 7 4 9-6 Gindolin KH

G . Dryhurst， e t a 1. ,J. A π . C h e m . s o c. 1 9 8 9, 111 9 lx 7 經濟部智慧財產局員工消費合作社印製G. Dryhurst, e t a 1., J. A π. C h e m. So c. 1 9 8 9, 111 9 lx 7

HP NHP N

L 10 (請先閱讀背面之注意事項再填寫本頁)L 10 (Please read the notes on the back before filling this page)

本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）This paper size applies to China National Standard (CNS) A4 (210 X 297 mm)

510900 A7 __B7_ 五、發明說明（9 ) M . dn Ischia，e t al. ,Tetrahedron 1 9 8 7,4 3 , 4 3 1 -510900 A7 __B7_ V. Description of the invention (9) M. dn Ischia, e t al., Tetrahedron 1 9 8 7, 4 3, 4 3 1-

4 3 4掲示化合物M 發JB.之記述本發明提供如下式I化合物式中 A r為4 3 4 shows the description of compound M and JB. The present invention provides the following compounds of formula I, where A r is

Z2 --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製Z2 -------------------- Order --------- line (please read the precautions on the back before filling this page) Intellectual Property Bureau of the Ministry of Economic Affairs Printed by Employee Consumer Cooperative

或or

A為氫，鹵素，或0H ; B及D各為氫，鹵素，CN，C i - 8烷基，芳基，C 6_12 芳 -1 1 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 B7_ 五、發明說明（、。）烷基，Ci-e羥烷基，（：6-12羥芳烷基，C3-8璟烷基，硝基，胺基，-Nl^R1' -NpCOR1^, (請先閱讀背面之注意事項再填寫本頁) C3-8環烷胺基，嗎啉基，呋喃-2-基，呋喃-3-基，晴 lb 盼-2 -基，瞎吩-3 -基，-C 0 R 或0 R ; R 為氫，Ci-e 烷基，COR1，-(CHynCO^R1, -CH(Rla) C〇2Rl, S02R1， - ( CH2)raCH (OH) C02R1 CH2)raCOC〇2R1 , (CHy^CH^CHCO〆，或（CHymOUHJoCOy1; R1為氫或Ci-6烷基；芳烷基，芳基或CH2 CO2 ϋ1 =; 為氫或Ci-8烷基·， E 為 S，SO , SO 2 , 0 或 NRlc; X為氫，鹵素，Ci-e烷基，C2-7烯基，CN，芳基，A is hydrogen, halogen, or 0H; B and D are each hydrogen, halogen, CN, Ci-8 alkyl, aryl, C 6_12 aryl-1 1-This paper size applies Chinese National Standard (CNS) A4 specifications ( 210 X 297 mm) 510900 A7 B7_ V. Description of the invention (, ...) Alkyl, Ci-e hydroxyalkyl, (: 6-12 hydroxyaralkyl, C3-8 fluoranyl, nitro, amine, -Nl ^ R1 '-NpCOR1 ^, (Please read the precautions on the back before filling this page) C3-8 cycloalkylamino, morpholinyl, furan-2-yl, furan-3-yl, sunny lb 2 -yl, blind phen-3 -yl, -C 0 R or 0 R; R is hydrogen, Ci-e alkyl, COR1,-(CHynCO ^ R1, -CH (Rla) C02R1, S02R1,-( CH2) raCH (OH) C02R1 CH2) raCOC〇2R1, (CHy ^ CH ^ CHCO〆, or (CHymOUHJoCOy1; R1 is hydrogen or Ci-6 alkyl; aralkyl, aryl or CH2 CO2 ϋ1 =; is hydrogen or Ci-8 alkyl ·, E is S, SO, SO 2, 0 or NRlc; X is hydrogen, halogen, Ci-e alkyl, C2-7 alkenyl, CN, aryl,

Ce_12芳烷基，Ci-e羥烷基，C8-i2羥芳烷基，Cb6 全氟烷基，Ci-e烷氣基，芳氣基；芳烷氣基，硝基，胺基，-NR2R2' -NR2C0R2a，C3-8環烷胺基，_啉基，Ci-e烷磺醯基，芳磺醯基，吡啶磺醯基，2-N，N-二甲胺乙磺醯基，-0CH2C02R &或-C 0 R2e ; Y為氫，鹵素，Ci-6烷基，芳基，（：6-12芳烷基，Cn 羥烷基，Ce-12 羥芳烷基，-OR3，SR3, NR3R3a，-C0R3b ，嗎啉或脈啶；經濟部智慧財產局員工消費合作社印制衣 R > R ，R ，R ，R ，各為氮，Ci-8 燒基，^6-12 芳烷基，或芳基；Ce_12 aralkyl, Ci-e hydroxyalkyl, C8-i2 hydroxyaralkyl, Cb6 perfluoroalkyl, Ci-e alkane, aryl, aralkyl, nitro, amine, -NR2R2 '-NR2C0R2a, C3-8 cycloalkylamino, _linenyl, Ci-e alkylsulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl, -0CH2C02R & or -C 0 R2e; Y is hydrogen, halogen, Ci-6 alkyl, aryl, (: 6-12 aralkyl, Cn hydroxyalkyl, Ce-12 hydroxyaralkyl, -OR3, SR3, NR3R3a, -C0R3b, morpholine or pyrimidine; printed clothing R > R, R, R, R, each of which is nitrogen, Ci-8 alkyl, ^ 6-12 aralkyl , Or aryl;

Rlbg C卜e烷基或芳基； 2b R 為氫，C i- e烷基； R2e及R3b各為C 烷基，芳基或C卜12芳烷基； -12- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）五、發明說明（Rlbg C alkyl or aryl; 2b R is hydrogen, Ci-e alkyl; R2e and R3b are each C alkyl, aryl or C12 alkyl; -12- This paper size applies to China Standard (CNS) A4 specification (210 X 297 mm) 5. Description of the invention (

I I 為氫，鹵素或OR 4 ; Α7 Β7 6 R4 為氫，C1-6烷基，-CH ( R5) W，-C ( CH3)2 C〇2R ，I I is hydrogen, halogen or OR 4; A7 B7 6 R4 is hydrogen, C1-6 alkyl, -CH (R5) W, -C (CH3) 2 C02R,

5*瞎唑旋-2，4-二_，CH(R7) (CH2)raC〇 2ί^， - P〇3(R6)2，-S〇2R6, -(CH2)pCH(0H)C02R6， (CH 2)pC0C02Ii6，（CHPpCl^CHCOaR6，或 -（CH2)p0 (CH2)q C〇2R5 * Blazol-2,4-bis-, CH (R7) (CH2) raC〇2ί ^, -P〇3 (R6) 2, -S〇2R6,-(CH2) pCH (0H) C02R6, ( CH 2) pC0C02Ii6, (CHPpCl ^ CHCOaR6, or-(CH2) p0 (CH2) q C〇2R

COR 6 6 經濟部智慧財產局員工消費合作社印製COR 6 6 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs

Rs為氫，C：l-6烷基，Ce-i2芳烷基，芳基，-(CH2) (1H -眯唑-4-基），-(CH2) (3-1H -吲 B朵基）， -CH2CH2 (1，3 -二氣-1，3 -二氫-異吲昤-卜基）， -CH2CH2 (卜氧-1, 3*"二氫-異吲昤-2-基），-CH2 (3 -Bft 啶基），-CH2CH2H，或-(CH2)n6; HhT^··、 HN^ HN^^i 6 為 H R 6aR7a，N R6a C 0 R7a |^JCH2)n， [^CH2)n , or W 為 C02R6, C0NH2 , COHHOH , CN，CONH ( CH2)2CN，5_ ^ 6b 7b 四唑，-P03( R6)2 , CH2〇H, CONR CHR # -CH2NR6bCHR7bC〇2R6，-CH2〇CHR7bC〇2R6, -CH2Br,或 C0NR6bCHR7bC02B6; R6 , R6a, R7，&為氫，C卜e烷基，或芳基；為氫或 C 0 R ; 较6<2為C 烷基或芳基； 7b R 為氫，C1-8院基，或Cl-6經烷基； z1及Z2各為氫，鹵素，CN, Ci-6焼基，芳基，C8-12 芳烷基，C3-8環烷基，硝基，胺基，-NR1 CORla, C3-8環烷胺基，嗎啉基，或〇R8 ,或Z1 -13- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）請先閱讀背 © 之注意事項再填寫本頁 f I I I I I訂線經濟部智慧財產局員工消費合作社印製 510900 A7 B7 五、發明說明（α) 及Z 2可以二烯單位共形成-C H = C R 9 - C R = C R 11 ; R 8 為氫，Ci-e烷基，或芳基； R 9 , 各為氫，Ci_-e烷基，芳基，鹵素，羥基，或Ci-8焼氯基； m = 1 〜4 ; η = 1或 2 ; Ρ = 1 〜4 ; q = 1 〜4 β 製藥容許鹽可由有機及無機酸所形成，如乙酸，丙酸，乳酸，檸檬酸，酒石酸，丁二酸，反丁烯二酸，順丁烯二酸，丙二酸，苦杏仁酸，羥基丁二酸，_酸，氫氯酸，氫溴酸，磷酸，硝酸，硫酸，甲磺酸，蔡磺酸，苯磺酸，甲苯磺酸，莰磺酸，及相似已知容許酸，其傺當本發明化合物含鹸基，如當R 5為-CH2 ( 3-吡啶基），或Y為嗎啉或含相似鹼基〇當本發明化合物含羧酸鹽或酚基，此鹽亦可由有機及無機鹸形成，宜為鹸金鼷鹽，如鈉，鋰或鉀。烷基含直鏈或分枝者。鹵素為溴，氯，氟及碘。芳基或芳烷基取代基之芳基宜為苯基或莆基；最宜為苯基。芳基部份可任意單，二或三取代以取代基選自Ci-s烷基，Ci-6烷氣基，三氟甲基，鹵素，C2-7烷氣羰基，烷胺基，及二烷胺基其中各烷基為，硝基，氡基，-C02H, C2-7烷羰氣基，及C2-7烷羰基。本發明化合物可含一個不對稱磺原子且部份本發明化 -14- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 510900 A7 _B7_ 五、發明說明（A ) (請先閱讀背面之注意事項再填寫本頁) 合物可含一以上不對稱中心，因而可含光學異構物及非對映異構物〇式I當無視立體化學時，本發明含此光學異構物及非對映異構物；及消旋及解析對映純R及S立體異構物；及其它R及S立體異構物混物及製藥容許鹽。本發明化合物亦可由限制或緩慢轉動芳基-三環或芳基-二環單鍵而成直生異構物Utropisomer)。此限制轉動可得另一對掌中心而得對映體。當分子含另一對掌中心時，則存在非對映異構物且可由NMR及其它光學技術測知。式I當無視直生異構物立體化學時，本發明含此直生異構物（對映體及非對映異構物及消旋及解析純非對映異構_及非對映異構物混物及製藥容許鹽。本發明較佳化合物含式（I)化合物或其製藥容許鹽Rs is hydrogen, C: 1-6 alkyl group, Ce-i2 aralkyl group, aryl group,-(CH2) (1H -oxazol-4-yl),-(CH2) (3-1H-indodolyl) ), -CH2CH2 (1,3 -digas-1,3 -dihydro-isoindioyl-boxy), -CH2CH2 (dioxy-1, 3 * " dihydro-isoindio-2-yl) , -CH2 (3-Bft pyridyl), -CH2CH2H, or-(CH2) n6; HhT ^ ··, HN ^ HN ^^ i 6 is HR 6aR7a, N R6a C 0 R7a | ^ JCH2) n, [^ CH2) n, or W is C02R6, C0NH2, COHHOH, CN, CONH (CH2) 2CN, 5_ ^ 6b 7b tetrazole, -P03 (R6) 2, CH2〇H, CONR CHR # -CH2NR6bCHR7bC〇2R6, -CH2. CHR7bC02R6, -CH2Br, or CONR6bCHR7bC02B6; R6, R6a, R7, & is hydrogen, C alkyl, or aryl; is hydrogen or C 0 R; more than 6 < 2 is C alkyl or aryl; 7b R is hydrogen, C1-8 alkyl, or Cl-6 via alkyl; z1 and Z2 are each hydrogen, halogen, CN, Ci-6fluorenyl, aryl, C8-12 aralkyl, C3-8 ring Alkyl, nitro, amine, -NR1 CORla, C3-8 cycloalkylamino, morpholinyl, or OR8, or Z1 -13- This paper size applies to China National Standard (CNS) A4 (210 X 297) Mm) Please read the precautions for © before filling out this page f IIIII Printed by the Consumer Property Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7 V. Description of invention (α) and Z 2 can be co-formed by diene units -CH = CR 9-CR = CR 11; R 8 is hydrogen, Ci- e alkyl, or aryl; R 9, each is hydrogen, Ci_-e alkyl, aryl, halogen, hydroxyl, or Ci-8fluorenyl; m = 1 to 4; η = 1 or 2; P = 1 to 4; q = 1 to 4 β Pharmaceutically acceptable salts can be formed from organic and inorganic acids, such as acetic acid, propionic acid, lactic acid, citric acid, tartaric acid, succinic acid, fumaric acid, maleic acid, Malonic acid, amygdalic acid, hydroxysuccinic acid, hydrochloric acid, hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, methanesulfonic acid, tsailic acid, benzenesulfonic acid, toluenesulfonic acid, sulfonic acid, And similar known permissible acids, when the compound of the present invention contains a fluorenyl group, such as when R 5 is -CH2 (3-pyridyl), or Y is morpholine or contains a similar base; when the compound of the present invention contains a carboxylate Or phenolic, this salt can also be formed from organic and inorganic rhenium, preferably osmium gold osmium salt, such as sodium, lithium or potassium. Alkyl contains straight chain or branch. Halogen is bromine, chlorine, fluorine and iodine. The aryl group of the aryl or aralkyl substituent is preferably phenyl or fluorenyl; most preferably, phenyl. The aryl moiety may be mono-, di-, or tri-substituted with a substituent selected from Ci-s alkyl, Ci-6 alkylamino, trifluoromethyl, halogen, C2-7 alkylcarbonyl, alkylamino, and di Alkylamino groups in which each alkyl group is nitro, fluorenyl, -C02H, C2-7 alkylcarbonyl, and C2-7 alkylcarbonyl. The compound of the present invention may contain an asymmetric sulfonic atom and part of the present invention is -14- This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) ------------ -------- Order --------- line (please read the precautions on the back before filling this page) 510900 A7 _B7_ 5. Description of the invention (A) (Please read the precautions on the back first (Fill in this page again) The compound may contain more than one asymmetric center, so it may contain optical isomers and diastereomers. Formula I When the stereochemistry is ignored, the present invention contains this optical isomer and diastereomer Isomers; and racemic and resolved enantiomerically pure R and S stereoisomers; and other R and S stereoisomer mixtures and pharmaceutically acceptable salts. The compounds of the present invention may also be orthotropic (Utropisomer) by limiting or slowly rotating an aryl-tricyclic or aryl-bicyclic single bond. This restricted rotation results in another pair of palm centers and the enantiomer. When the molecule contains another pair of palm centers, diastereomers are present and can be detected by NMR and other optical techniques. Formula I When the stereochemistry of the orthoisomer is disregarded, the present invention contains the orthoisomer (enantiomers and diastereomers, and racemic and resolved pure diastereomers and diastereomers Compounds and pharmaceutically acceptable salts. Preferred compounds of the present invention include a compound of formula (I) or a pharmaceutically acceptable salt thereof.

經濟部智慧財產局員工消費合作社印製式中 A為氫或_素； B及D各為氫，鹵素，CN，C i 烷基，芳基，C e-12芳烷基，分枝烷基，C3-8璟烷基，硝基或0R; R為氫或C 烷基； -15- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 B7 五、發明說明（4 ) E為S或0或； (請先閱讀背面之注意事項再填寫本頁) X為氫，鹵素，Ci-e烷基，CN, Ci-8全氟烷基，Ci-e 烷氧基，芳氯基；芳烷氯基，硝基，胺基，-NR2 β2' - NR2C0R2a, C3-8環烷胺基，嗎啉基，Ci-6烷磺醯基，芳磺醯基，毗啶磺醯基，2-N, N -二甲胺乙磺醯基， R 1，R la，R2，R 2a , R 3 及 R 3a各為氫，C i - e 烷基， C 6-12芳烷基，或芳基； Y 為氫，鹵素，-OR3, SR3，NR3R3a，或嗎啉基； C為氫，鹵素或0R 4 ; R4 為氫，C1-6烷基，-CH ( R5) W，-C ( CH3)2C02R6, 5-B塞唑啶-2，4-二酮，CH(R7) (CH2)mC02R6, -C0R6, 5 6 c. -P〇3(K >2> -S02R , -(〇Η2)ρ〇Η(ΟΗ)σ〇2Ε^ , ~(CH 2 )pC0C02R6，一 (CH2)pCH = CHC02R6,或 -(CH2)p〇(CH2)qC〇2R6 ；為氫，Ci-s烷基，Ce-u芳烷基，芳基，_(CH2) (1H-眯唑一4-基），-(CH 2 ) ( 3-1H-U 引時基）， -CH 2 CH 2 ( 1 , 3 -二氣一1 , 3 -二氯一異 B3| (朵一2 -基），經濟部智慧財產局員工消費合作社印製 -C Η 2 C Η 2 (1一氣一1, 3 -二氮一異 I引费朵一2 -基），-C Η 2 (3 -吡啶基）； W 為 C〇2R6，C0NH2，-C0MH0H，或 5-四唑，或 C0NR6bCHR 7bC02R6 ； R6, R R7，R7aft R7b各為氫，C卜6烷基，或芳基； Z1及Z2各為氫，齒素，CN，Ci-e烷基，芳基，C6_12 -16- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 _B7_ 五、發明說明（^ ) 芳烷基，C3-8環烷基，硝基，胺基， -!^1(：01^1'(：3-8環烷胺基，嗎啉基，或01{8，或2 及^可以二烯單位共形成- CH = CR9 -CRiG =CRU ; R9及RiQ各為氫或Ci-e烷基； p = 1 〜4 ; q = 1 〜4 β 本發明更佳化合物含式（I)化合物或其製藥容許鹽：In the printed version of the Employee Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, A is hydrogen or hydrogen; B and D are each hydrogen, halogen, CN, C i alkyl, aryl, C e-12 aralkyl, branched alkyl , C3-8 alkyl, nitro or OR; R is hydrogen or C alkyl; -15- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 510900 A7 B7 V. Description of the invention (4) E is S or 0 or; (Please read the notes on the back before filling this page) X is hydrogen, halogen, Ci-e alkyl, CN, Ci-8 perfluoroalkyl, Ci-e alkoxy Aryl, chloro, aralkyl, nitro, amine, -NR2 β2 '-NR2C0R2a, C3-8 cycloalkylamino, morpholinyl, Ci-6 alkylsulfonyl, arylsulfonyl, phenyl Pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl, R 1, R la, R2, R 2a, R 3 and R 3a are each hydrogen, C i-e alkyl, C 6-12 Aralkyl, or aryl; Y is hydrogen, halogen, -OR3, SR3, NR3R3a, or morpholinyl; C is hydrogen, halogen or OR 4; R4 is hydrogen, C1-6 alkyl, -CH (R5) W, -C (CH3) 2C02R6, 5-B oxazoline-2,4-dione, CH (R7) (CH2) mC02R6, -C0R6, 5 6 c. -P〇3 (K > 2 >- S02R,-(〇Η2) ρ〇Η (ΟΗ) σ〇2Ε ^, ~ (CH 2) pC0C02R6, one (CH2) pCH = CHC02R6, or-(CH2) p〇 (CH2) qC〇2R6; is hydrogen, Ci-s alkyl, Ce-u aromatic Alkyl, aryl, _ (CH2) (1H-oxazole-4-yl),-(CH 2) (3-1H-U time-initiating group), -CH 2 CH 2 (1, 3 -digas 1, 3 -Dichloro-iso-iso-B3 | (Duo- 2--based), printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs -C Η 2 C Η 2 (Duo- 2 -yl), -C Η 2 (3-pyridyl); W is Co2R6, CONH2, -COMHOH, or 5-tetrazole, or CONR6bCHR 7bC02R6; R6, R R7, R7aft R7b are each hydrogen, C6 alkyl, or aryl; Z1 and Z2 are each hydrogen, dentin, CN, Ci-e alkyl, aryl, C6_12 -16- This paper size applies Chinese National Standard (CNS) A4 specifications (210 X 297 mm) 510900 A7 _B7_ V. Description of the invention (^) Aralkyl, C3-8 cycloalkyl, nitro, amine,-! ^ 1 (: 01 ^ 1 '(: 3-8cycloalkylamino) , Morpholinyl, or 01 {8, or 2 and ^ can be co-formed by diene units-CH = CR9 -CRiG = CRU; R9 and RiQ are each hydrogen or Ci-e alkyl; p = 1 to 4; q = 1 to 4 β The better compound of the present invention contains formula I) compound or a pharmaceutically tolerable salt thereof:

-------------% (請先閱讀背面之注意事項再填寫本頁) 訂---- 經濟部智慧財產局員工消費合作社印製式中 Α為氫； B及D各為鹵素，Ci-6烷基，芳基，C6-i2 芳烷基，或C3-8環烧基； E為S或0或； X為氫，鹵素，Ci-e烷基，Ci-6全氟烷基，烷氧基，芳氧基；Ce-^芳烷氧基，芳磺醯基； Y為氫或NPR2，或嗎啉基； R1及R2各為氫或Ci-e烷基，Ce-12芳烷基，或芳基； C 為 0 R 4 ; -17- 線Ψ 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印製 510900 A7 B7___ 五、發明說明（4 ) R 4 為氫，C 烷基，-CH ( R5 ) W，或唑啶-2 , 4- 二酮；-------------% (Please read the notes on the back before filling out this page) Order ---- In the printed format of the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, A is hydrogen; B and D is each halogen, Ci-6 alkyl, aryl, C6-i2 aralkyl, or C3-8 cycloalkyl; E is S or 0 or; X is hydrogen, halogen, Ci-e alkyl, Ci- 6Perfluoroalkyl, alkoxy, aryloxy; Ce- ^ aralkoxy, arylsulfonyl; Y is hydrogen or NPR2, or morpholinyl; R1 and R2 are each hydrogen or Ci-e alkyl , Ce-12 aralkyl, or aryl; C is 0 R 4; -17- line This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) Employees ’Cooperatives, Intellectual Property Bureau, Ministry of Economic Affairs Print 510900 A7 B7___ 5. Description of the invention (4) R 4 is hydrogen, C alkyl, -CH (R5) W, or oxazodin-2, 4-dione;

Rs為氫，烷基，Ce-i2芳烷基，芳基，-(CH2) (3-1Η-Β3Ι»朵基），-CH 2 CH 2 (1, 3 -二氣一1, 3 -二氫-異吲呤-2-基）或- CH2CH2 (卜氣-1，3 -二氫-異 B3I B朵-2 -基）； W ^ ~C0 2 R 6，-C0NH 2，-C0NH0H , 5-四唑，-P03(R6)2 ，-C0NR 6 CHR6 C02 R6 ； R 6為氫或C卜8烷基； Z1及Z2可以二烯單位共形成- CH=CH-H=CH-。本發明又更佳化合物含如下化合物或其製藥容許鹽： (R) -2-[2，6 -二溴-4- (9 -漠-2，3 -二甲基-萘駢 [2，3-b]-B塞盼-4-基）苯氧基卜3-苯丙酸； (1〇-2-[2-溴-4-(9-溴-2，3-二甲基-萘駢[2，3-1)] -瞎盼-4-基）-6-乙基-苯氧基卜3-苯丙酸； (R) -2-[4-(9-溴-2, 3-二甲基-萘駢[2，3-b]-瞎盼 -4-基）-2, 6-二甲基-苯氣基]-3-苯丙酸； (R) -2-[4-(9 -溴-2，3-二甲基-蔡駢[2，3-b]-瞎盼 -4 -基）-2 -氟苯氧基]-3 -苯丙酸； 4- (9-溴-2，3-二甲基-萘勝[2，3-b] -瞎玢-4-基）-2， 6-二異丙苯氣基】-乙酸； ({〇-2-[2-溴-4-(9-溴-2，3-二甲基-蔡駢[2，3-1)]-瞎盼-4-基）-6-第二丁基-苯氣基卜3-苯丙酸； (R ) - 2 - [ 2 -溴-4 - ( 9 -溴-2，3 -二甲基-萘駢[2，3 - b ] -18- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） ------------§------- —訂---------線 (請先閱讀背面之注意事項再填寫本頁) 510900 A7 B7 五、發明說明（π ) (請先閱讀背面之注意事項再填寫本頁) -B塞盼-4-基）-6 -異丙基-苯氣基1-3 -苯丙酸； (1〇-2-[2-溴-4-(9_溴-2，3-二甲基-萘駢[2，3-1)]-瞎盼-4-基）-2-環戊基-苯氣基卜3-苯丙酸； (R) -2-[4-(9-溴-2，3-二甲基-萘駢[2，3-b]-P室盼 -4 -基）-6 -異丙基-苯氧基]-3 -苯丙酸； (R) -2-[4-(9-溴-2, 3-二甲基-萘駢[2，3-b】-瞎盼 -4-基）-2-環戊基-苯氣基卜3-苯丙酸； (R) -2-[2，6-二溴-4- (2，3-二甲基-9-苯磺醯基-綦駢[2, 3-b卜_盼-4-基）苯氧基卜3 -苯丙酸； (1?)-2-[2，6-二溴-4-(9-溴-2，3-二甲基-萘駢 [2, 3-b卜_盼-4 -基）苯氣基卜3 -苯丁酸； (8)-2-[2,6-二溴-4-(9-溴-2，3-二甲基-蔡駢 [2，3-b]-晴盼-4-基）苯氣基]-3 -苯丁酸； 2-[2, 6 -二溴-4- (9 -溴-3-甲基-2-嗎啉-4-基甲基-萘駢[2，3-b卜瞎盼-4-基）苯氣基卜3-苯丙酸； (!?)-2-[2，6-二溴-4-(2，3-二甲基-9-苯磺醯基-萘駢[2，3-b]-_盼-4-基）苯氯基卜丙酸； [2-溴-4-(9-溴-2，3-二甲基-萘駢[2,3-1)]-_盼-4-基）-2-硝苯氧基]-3-苯丙酸；經濟部智慧財產局員工消費合作社印製 2，6 -二溴- 4-(9 -溴-2，3_ 二甲基駢[2，3-b]_Bt 盼 -4 -基）酚； 2-溴-4- (9-溴，2，3 -二甲基駢[2，3-b卜睹盼-4-基） - 2-硝酚； (R) -2-[2, 6 -二溴- 4-(9-溴-2-二乙胺甲基-3-甲基- -19- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 _B7_ 五、發明說明（d ) 蔡駢[2，3-b]-瞎盼-4-基）苯氣基卜3-苯丙酸； (趵-2-[2，6-二溴-4-(2,3-二甲基-萘駢[2,3-1)卜呋喃-4-基）苯氣基卜3-苯丙酸； (2R) -2-[4-(9 -溴-2, 3 -二甲基-萘駢[2，3-b] -晴盼 - 4-基）-2，6-二異丙苯氣基卜3-苯丙酸； (R) -2-[4-(9-溴-2, 3-二甲基-萘駢[2，3-b卜睹盼 -4-基）-2，6-二乙苯氣基卜3-苯丙酸； {(2R) -2-[4-(9-溴-2，3-二甲基-蔡駢[2，3-b】-瞎盼-4-基）-2, 6-二甲苯氧基]-3-苯丙_胺基}乙酸； {(2R) -2-[4-(9 -漠-2，3-二甲基-蔡駢[2，3-b]-睹盼-4-基）-2, 6-二乙苯氣基卜3-苯丙醯胺基}乙酸；本發明化合物可下列流程，使用市售可得物或可由文獻刊載方法製得之原料。此流程列出本發明代表化合物之製法。 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 -20- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 B7 經濟部智慧財產局員工消費合作社印製五、發明說明（ΗRs is hydrogen, alkyl, Ce-i2 aralkyl, aryl,-(CH2) (3-1Η-Β3Ι »aryl), -CH 2 CH 2 (1, 3 -digas-1, 3 -di Hydrogen-isoindin-2-yl) or -CH2CH2 (Buqi-1,3-dihydro-isoB3I B-do-2 -yl); W ^ ~ C0 2 R 6, -C0NH2, -C0NH0H, 5 -Tetrazole, -P03 (R6) 2, -CONR 6 CHR6 C02 R6; R 6 is hydrogen or C 8 alkyl; Z1 and Z2 can be co-formed in diene units-CH = CH-H = CH-. A further preferred compound of the present invention contains the following compound or a pharmaceutically acceptable salt thereof: (R) -2- [2,6-dibromo-4- (9-mo-2,3-dimethyl-naphthalene} [2,3 -b] -B-Seppan-4-yl) phenoxyb 3-phenylpropanoic acid; (10-2- [2-bromo-4- (9-bromo-2,3-dimethyl-naphthalene) [2,3-1)]-blaze-4-yl) -6-ethyl-phenoxyb 3-phenylpropionic acid; (R) -2- [4- (9-bromo-2, 3- Dimethyl-naphthalenepyrene [2,3-b] -blaze-4-yl) -2, 6-dimethyl-phenylamino] -3-phenylpropanoic acid; (R) -2- [4- (9-bromo-2,3-dimethyl-Ceamidine [2,3-b] -blaze-4-yl) -2-fluorophenoxy] -3 -phenylpropanoic acid; 4- (9- Bromo-2,3-dimethyl-naphthyl [2,3-b] -benzylidene-4-yl) -2,6-dicumylamino] -acetic acid; ({〇-2- [2 -Bromo-4- (9-bromo-2,3-dimethyl-Ceamidine [2,3-1)]-blaze-4-yl) -6-second butyl-phenylamino Phenylpropionic acid; (R)-2-[2 -Bromo-4-(9 -Bromo-2,3-dimethyl-naphthalene [2,3-b] -18- CNS) A4 specification (210 X 297 mm) ------------ § --------Order --------- line (Please read the note on the back first Please fill in this page for matters) 510900 A7 B7 V. Description of Invention (π) (please first Read the notes on the back and fill in this page again) -B-Sepan-4-yl) -6-Isopropyl-phenylamino-1-3-phenylpropanoic acid; (1〇-2- [2-Bromo-4- (9-bromo-2,3-dimethyl-naphthalenepyrene [2,3-1)]-blazepan-4-yl) -2-cyclopentyl-benzyl 3-phenylpropanoic acid; (R ) -2- [4- (9-Bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] -P-copan-4-yl) -6-isopropyl-phenoxy]- 3-Phenylpropionic acid; (R) -2- [4- (9-Bromo-2, 3-dimethyl-naphthalenepyrene [2,3-b] -blaze-4-yl) -2-cyclopentane Phenyl-benzyl 3-phenylpropanoic acid; (R) -2- [2,6-dibromo-4- (2,3-dimethyl-9-benzenesulfonyl-fluorenyl-fluorene [2, 3 -b bu_pan-4-yl) phenoxy bu 3-phenylpropanoic acid; (1?)-2- [2,6-dibromo-4- (9-bromo-2,3-dimethyl- Naphthalene hydrazine [2, 3-b-b-pan-4 -yl) phenylamino-b-butyric acid; (8) -2- [2,6-dibromo-4- (9-bromo-2,3 -Dimethyl-Ceamidine [2,3-b] -qingpan-4-yl) phenylamino] -3 -phenylbutanoic acid; 2- [2, 6-dibromo-4- (9 -bromo- 3-methyl-2-morpholin-4-ylmethyl-naphthalenepyrene [2,3-b-blazepan-4-yl) phenylaminophenyl 3-phenylpropanoic acid; (!?)-2- [ 2,6-dibromo-4- (2,3-dimethyl-9-benzenesulfonyl-naphthalene [2,3-b] -_ pan-4-yl) phenylchloropropionic acid; [ 2-bromo-4- (9-bromo-2,3-dimethyl -Naphthalene [2,3-1)] -_ pan-4-yl) -2-nitrophenoxy] -3-phenylpropanoic acid; 2,6-dibromo printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs -4- (9-bromo-2,3-dimethylfluorene [2,3-b] _Bt pan-4 -yl) phenol; 2-bromo-4- (9-bromo, 2,3-dimethylfluorene [2,3-b Bupan-4-yl)-2-nitrophenol; (R) -2- [2, 6-Dibromo-4- (9-bromo-2-diethylaminemethyl-3) -Methyl- -19- This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 510900 A7 _B7_ V. Description of the invention (d) Cai Yan [2,3-b] -Banpan-4 -Yl) benzylphenyl 3-phenylpropanoic acid; (fluorene-2- [2,6-dibromo-4- (2,3-dimethyl-naphthalenepyrene [2,3-1) benzofuran-4 -Yl) benzylphenyl 3-phenylpropanoic acid; (2R) -2- [4- (9-bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] -qingpan- 4- Phenyl) -2,6-dicumylairyl 3-phenylpropionic acid; (R) -2- [4- (9-bromo-2, 3-dimethyl-naphthalene} [2,3-b Bu Jianpan-4-yl) -2,6-diethylphenylaminophenyl 3-phenylpropanoic acid; {(2R) -2- [4- (9-Bromo-2,3-dimethyl-Cetraline [2,3-b] -blaze-4-yl) -2, 6-xylyloxy] -3-phenylpropanylamino} acetic acid; {(2R) -2- [4- (9-Mo -2,3-dimethyl-Cai Yan [2,3-b] -Lanpan -4-yl) -2,6-diethylphenylaminophenyl 3-phenylpropanylamino} acetic acid; The compounds of the present invention can be prepared in the following schemes using commercially available materials or materials prepared by publication methods. This scheme lists the preparation methods of the representative compounds of the present invention. (Please read the precautions on the back before filling this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs -20- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 510900 A7 B7 Ministry of Economic Affairs Printed by Intellectual Property Bureau's Consumer Cooperatives

)Q) Q

DD

(Π) (III) η(Π) (III) η

反應流程1中，2, 3 -二甲睹盼（ΙΙ:Ε為S)可由市售可得3-甲基瞎吩-羧醛，使用Wolff-Kishner條件（腈再於K0H /乙二醇回流。化合物（II:E為S或0)可處理以 1〜1.3莫耳當量之烷鋰劑，如Μ-丁鋰，最宜於非質子溶劑（如THF)，於-78°C〜室溫，於惰氣如氮或氬下反應可得2-鋰化盼或呋喃衍生物。將此鋰化物與一以上莫耳當量之苄醛，於-78°C〜室溫反應5分至3小時可得式（I I I ·· Q = 0 Η ; E為S或0 )之化合物。（I I I)之羥基 (Q = 0H)可由還原方法去除，如使用鉛觸媒之氫化以得 -2 1 - ------------§------- —訂---------線 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印製 510900 A7 B7 五、發明說明（w) 式（III:Q = H;E為S或0)之化合物，但最易使用Nutaitis 等人(0 r g . Prep· And Proceed. I n t . 1 9 9 1, 2 3 , 4 0 3 - 411)方法去除，其中將（III:Q = H;E為S或0)，於適當溶劑如***，THF或二氯甲烷，於0°C〜室溫下攪拌以1〜1G莫耳當量之硼氫化鈉，於15分至3小時内緩慢加入1-50莫耳當量之三氟乙酸可得式（III:Q = H;E為S或0) 之化合物。此外，含化合物（II :E為S或0)之2-鋰化物於如T H F之非質子溶劑，可於-7 8 °C〜室溫下，與一以上莫耳當量之苄鹵（如苄溴（PhCH2Br))反應直接提供式（ΙΙΙ··〇 = Η;Ε為S或0)之化合物。式（III:Q = H;E為S或0)化合物可醯化以一以上莫耳當量市售可得式（IV:A，B, C, D為Η或Ome; A，B, C， D組合取代基含一以上OMe基，但不含多於3個OMe基）苄醯氯可得式（V: A, B， C， D為Η或OMe; A， B, C, D組合取代基含一以上〇Me基，但不含多於3個0 Me基；E為S 或0)之化合物。此藤化最易於使用1〜5莫耳當量之路易士酸觸媒，如四氯化錫或氯化銨，於如二氯甲烷，1 ，2 -二氯乙烷或二硫化磺之惰性溶劑，於-78 °C〜室溫下進行。式（V: A, B， C， D為 Η或 OMe; A, B， C， D組合取代基含一以上OMe基，但不含多於3個OMe基；E為S或0)化合物之環化一般宜使用1〜10莫耳當量之強路易士酸，如三鹵硼烷，最宜為三溴硼烷。反應宜於-78 °C〜室溫，或加熱至5fl °C，於鹵烴瀋劑如二氯甲烷，於惰氣如氮 -22- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） ------------§------- 丨訂---------線 (請先閱讀背面之注意事項再填寫本頁) 510900 A7 _B7___ 五、發明說明（Μ ) 或氬下進行。其不僅會環化及芳環化並同時失水，且使突出之甲氯基之去甲基化而得式（la: A, B，C, D為Η 或OH; A, B, C, D取代基組合含一以上0Η基，但不含多於3個0H基；E為S或0)化合物。仿反瞧流程1,式（Ia:A為Η; B，D為C1-6烷基或氟； C為OH; E為S或0)化合物可由式（III:Q = H;E為S或0) 化合物及適當苄醯氯（IV: A為Η; B, D為烷基或氟 ;C.OMe)為原料。苄 _氯（IV: A 為 Η; B, D 為烷基或氟；C為OMe)可由相對苄酸，依標準方法使用草醯氯及磺醯氯製得。苄醯氯（IV: A為Η; B, D為Ci-6烷基或氟；C為0 Me)之苄酸原料為市售可得或可由已知方法製得。例如，苄醯氯（IV: A為Η ; B, D為異丙基；C 為OMe)之酸原料可使用Schuster等人，J. Org. Chenu 1988, 53， 5819之修飾法製得。將市售可得2, 6 -二異丙酚於4位溴化（溴/乙酸），甲基化（碘甲烷/碳酸鉀/DMF)，與正丁鋰反應使鹵化鋰交換，將所得有機鋰與二氧化磺反應可得3，5 -二異丙基-4 -甲氯苄酸。 --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 反應流稈2In Reaction Scheme 1, 2,3-dimethylformanline (III: Ε is S) is commercially available as 3-methylbenzophene-carboxaldehyde, using Wolff-Kishner conditions (nitrile and KOH / ethylene glycol reflux) . Compound (II: E is S or 0) can process 1 ~ 1.3 mol equivalent of lithium alkane agent, such as M-butyl lithium, most suitable for aprotic solvents (such as THF), at -78 ° C ~ room temperature The reaction can be performed under an inert gas such as nitrogen or argon to obtain a 2-lithiation hope or a furan derivative. This lithium compound is reacted with more than one molar equivalent of benzaldehyde at -78 ° C ~ room temperature for 5 minutes to 3 hours Compounds of formula (III ·· Q = 0 Η; E is S or 0) can be obtained. The hydroxyl group of (III) (Q = 0H) can be removed by reduction method, such as hydrogenation using lead catalyst to obtain -2 1-- ----------- § ------- --Order --------- line (Please read the precautions on the back before filling this page) This paper size applies to China Standard (CNS) A4 (210 X 297 mm) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7 V. Description of the invention (w) Compounds of formula (III: Q = H; E is S or 0), But it is easiest to use Nutaitis et al. (0 rg. Prep · And Proceed. Int. 1 9 9 1, 2 3, 4 0 3-411) method, in which (III: Q = H; E is S or 0), in a suitable solvent such as ether, THF or dichloromethane, and stirred at 0 ° C ~ room temperature to 1 ~ 1G Mol An equivalent of sodium borohydride is slowly added in 1 to 50 mol equivalents of trifluoroacetic acid over 15 minutes to 3 hours to obtain a compound of formula (III: Q = H; E is S or 0). In addition, the compound (II : E is S or 0) 2-lithium compound in an aprotic solvent such as THF, can be reacted with more than one molar equivalent of benzyl halide (such as benzyl bromide (PhCH2Br)) at -78 ° C ~ room temperature Compounds of formula (III, ·· = =; E is S or 0) are provided directly. Compounds of formula (III: Q = H; E is S or 0) Compounds can be converted to commercially available formulae with one or more molar equivalents ( IV: A, B, C, D is fluorene or Ome; A, B, C, D combined substituents contain more than one OMe group, but do not contain more than 3 OMe groups. , B, C, D is fluorene or OMe; A, B, C, D is a compound containing more than one OMe group but not more than three 0 Me groups; E is S or 0). It is easiest to use 1 to 5 mole equivalents of Lewis acid catalysts, such as tin tetrachloride or ammonium chloride, such as methylene chloride, 1, 2-Dichloroethane or sulfur disulfide inert solvent, at -78 ° C ~ room temperature. Formula (V: A, B, C, D is Η or OMe; A, B, C, D combined substitution The group contains more than one OMe group, but does not contain more than three OMe groups; E is S or 0) The cyclization of compounds is generally suitable to use 1 to 10 mol equivalents of strong Lewis acids, such as trihaloborane, the most suitable Tribromoborane. The reaction is suitable at -78 ° C ~ room temperature, or heated to 5fl ° C, in a halocarbon precipitation agent such as dichloromethane, in an inert gas such as nitrogen-22. This paper size applies Chinese National Standard (CNS) A4 specifications (210 X 297 mm) ------------ § ------- 丨 Order --------- Line (Please read the precautions on the back before filling this page) 510900 A7 _B7___ 5. Description of the Invention (M) or under argon. It will not only cyclize and aromatic cyclize and lose water at the same time, but also demethylate the prominent methyl chloride group to obtain the formula (la: A, B, C, D is Η or OH; A, B, C, The D substituent combination contains more than one fluorenyl group, but does not contain more than three OH groups; E is S or 0). Analogous to Scheme 1, the formula (Ia: A is Η; B, D is C1-6 alkyl or fluorine; C is OH; E is S or 0) The compound can be represented by formula (III: Q = H; E is S or 0) Compound and appropriate benzamidine chloride (IV: A is Η; B, D is alkyl or fluorine; C.OMe) as raw materials. Benzyl chloride (IV: A is Η; B, D is alkyl or fluorine; C is OMe) can be made from relatively benzoic acid using chloral chloride and sulfonyl chloride according to standard methods. Benzylphosphonium chloride (IV: A is fluorene; B, D is Ci-6 alkyl or fluorine; C is 0 Me) The benzyl acid raw material is commercially available or can be prepared by known methods. For example, benzamidine chloride (IV: A is Η; B, D is isopropyl; C is OMe) can be prepared by the modification method of Schuster et al., J. Org. Chenu 1988, 53, 5819. Commercially available 2,6-dipropofol is brominated (bromo / acetic acid), methylated (iodomethane / potassium carbonate / DMF) at the 4-position, reacted with n-butyllithium to exchange lithium halides, and the obtained organic Lithium and sulphur dioxide can be reacted to obtain 3,5-diisopropyl-4-methylchlorobenzyl acid. -------------------- Order --------- Line (Please read the precautions on the back before filling this page) Reaction Stream 2

本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印製 510900 A7 B7_ 五、發明說明（％) 反應流程2中其它式（I)化合物衍生物可依下法製得。式（lb: B，D，X為Η·, C為0Η;Ε為S或0)酚（反應流程2)碘化為式（lb : Β，D為I ; X為Η ; C為OH ; Ε為 S或0)二碘酚，其傣使用2莫耳當量以上碘，於存在2莫耳當量以上如NaOH之鹼金屬氫氧化物，於如甲醇之醇溶劑，於-20°C至室溫下反應同樣地，單碘® (lb: B為 I; X, D 為 H; C 為 OH; E為 S或 0)可由式（lb: B，D，X 為Η ; C為0 Η ; E為S或0 )(反應流程2 )，使用1〜1 · 5莫耳當量碘，於存在1莫耳當量以上如^01!之_金屬氫氧化物，於如甲醇之醇溶劑，於-2 ϋ °C至室溫下反應而得。單碘酚（lb: B為I; X，D為H; C為OH; E為S或0)或二碘酚（lb·· B，D為I; X為H; C為OH; E為S或0)可轉為相對式（lb: B為I; X, D為H; C為OMe; E為S或0)或 (lb: B, D為I; X為H; C為OMe; E為S或0)之甲醚衍生物。其傺由將酚與適當甲基化劑，如1莫耳當量以上甲基碘或二甲硫酸鹽，使用如鹸金屬磺酸鹽或氫氧化物之鹼（如磺酸鉀或氫氣化鈉），於適當溶劑如THF，DMF或 D M S 0反應而得。此反應一般於0〜6 0 °C下進行。式（lb: B為I; X，D為H; C為OMe; E為S或0)之單碘甲醚衍生物或式（lb: B，D為I; X為H; C為OMe; E為S 或0 )之二碘甲醚可與1莫耳當量以上氰化銅（I)反應 (對於單碘物）或與2莫耳當量以上氰化銅（I)反應 (對於二碘物）反應而得式（lb·· B為I ·，X，D為Η ; C為 OMe; Ε為S或0)之單氰甲醚或式（lb: B，D為I; X為Η; -24- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） ------I-------------訂·-------- (請先閱讀背面之注意事項再填寫本頁) 510900 經濟部智慧財產局員工消費合作社印製 A7 B7 五、發明說明（w) c為OMe; E為S或0)之二気甲醚。氰化反應一般於100〜 2 5 0 °C下進行，使用非質子溶劑，如D M F ,卜甲基-2 -吡咯啶酮或ΗΜΡΑ。亦可使用贿啉或毗啶。式（Ib: 8為（^ ;D為Η或CN; X為H; C為〇Me; e為S或〇)之單或二氡甲氣物可轉為相對式（Ic : B為CN ; D為Η或CN ; X為Η ; E為S 或0)之單或二氡酚物（反應流程2 ),其僳使用檫準去甲基化方法，含使用含1荑耳當量以上三溴化硼或三氯化硼之二氯甲烷，於-7 8°C〜室溫之下反應；與過量純 Bft錠鹽酸鹽於1 9 0〜2 8 Q °C下反應；與於乙酸之氫溴酸於 0〜50 °C下反應；與含過量三甲矽烷溴或三甲矽烷碘之二氯甲烷，四氯化磺或乙睛，於-7 8〜5 0 °C下反應；與含碘化鋰之吡啶或睹啉，於1 0 0〜2 5 G °C下反*，及與i 莫耳當量以上乙基，甲基或異丙基硫氫，於存在1奠耳當量以上路易士酸如三氯化鋰或三氟化硼，於如二氡甲烷溶劑及-7 8 °C〜5 G °C下進行反應。式（lb: B為I; X，D為H; C為OMe; E為S或0)之擧蛾甲醚衍生物或式（lb: B，D為I; X為H; C為〇Me; E^S 或〇)之二碘甲醚（反應流程2)可與1莫耳當量以上 '漠化銅（I)反應（對於單碘物）或與2莫耳當量以上丨臭& 銅（I)反應（對於二碘物）反應而得式（Ib: X，D為H; C為OMe; E為S或0)之單溴甲醚或式（Ib. ，D.Br; X為H; C為OMe; E為S或0)之二漠甲酿。此凑 /碘互換反應一般於1 0 0〜2 5 0 °C下進行，使用非質子溶劑，如DMF，卜甲基-2_毗咯啶酮或HMPA。亦可使用本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 510900 A7 B7 五、發明說明（4) (請先閱讀背面之注意事項再填寫本頁) 或吡啶。式（Ib:B為Br; D為Η或Br; X為H; C為OMe; E 為S或0)之單或二溴甲氧物可轉為相對式（Ic: B為Br; D為Η或Br ; X為Η ; E為S或0)之單或二溴酚物（反應流程2 )，其係使用標準去甲基化方法，含使用1莫耳當量以上含三溴化硼或三氯化硼之二氯甲烷，於-7 8°C〜室溫之下反應；與過量純吡錠鹽酸鹽於1 9 G〜2 8 0 °C下反應 ;與於乙酸之氫溴酸於0〜5 0 °C下反應；與含過量三甲矽烷溴或三甲矽烷碘之於二氯甲烷，四氯化磺或乙腈下，於-7 8〜5 0 °C下與反應；與於吡聢或膣啉之碘化鋰，於1GG〜250 °C下，及與1莫耳當量以上乙基，甲基或異丙基硫氫，於存在1莫耳當量以上路易士酸如三氯化鋰或三氟化硼，於如二氯甲烷溶劑及-7 8 °C〜5 D °C下進行反應。This paper size is in accordance with China National Standard (CNS) A4 (210 X 297 mm) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7_ 5. Description of the invention (%) Derivation of other compounds of formula (I) in reaction scheme 2 Things can be made according to the law. Formula (lb: B, D, X is Η ·, C is 0Η; E is S or 0) phenol (Reaction Scheme 2) is iodinated to formula (lb: Β, D is I; X is Η; C is OH; E is S or 0) diiodophenol, which uses 2 mol equivalents or more of iodine, in the presence of 2 mol equivalents or more of alkali metal hydroxides such as NaOH, in alcohol solvents such as methanol, at -20 ° C to room temperature The reaction at the same temperature is the same, monoiodine ® (lb: B is I; X, D is H; C is OH; E is S or 0) can be represented by the formula (lb: B, D, X is Η; C is 0 Η; E is S or 0) (Reaction Scheme 2), using 1 to 1.5 mole equivalents of iodine, in the presence of more than 1 mole equivalent such as ^ 01! Metal hydroxide, in an alcohol solvent such as methanol, in- It is obtained by reaction at 2 ϋ ° C to room temperature. Monoiodophenol (lb: B is I; X, D is H; C is OH; E is S or 0) or diiodophenol (lb ·· B, D is I; X is H; C is OH; E is S or 0) can be converted to relative formula (lb: B is I; X, D is H; C is OMe; E is S or 0) or (lb: B, D is I; X is H; C is OMe; E is a methyl ether derivative of S or 0). This is done by mixing phenol with a suitable methylating agent, such as methyl iodide or dimethyl sulfate of 1 mol equivalent or more, using a base such as a sulfonium metal sulfonate or hydroxide (such as potassium sulfonate or sodium hydride) It is obtained by reacting in a suitable solvent such as THF, DMF or DMS 0. This reaction is generally carried out at 0 ~ 60 ° C. A monoiodomethyl ether derivative of formula (lb: B is I; X, D is H; C is OMe; E is S or 0) or formula (lb: B, D is I; X is H; C is OMe; E is S or 0) Diiodomethyl ether can react with copper (I) cyanide (1) or more (for monoiodide) or copper (I) cyanide (for diiodide) ) Reaction to obtain a formula (lb ·· B is I ·, X, D is Η; C is OMe; E is S or 0) or monocyanomethyl ether (lb: B, D is I; X is Η; -24- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ------ I ------------- Order · ------ -(Please read the notes on the back before filling this page) 510900 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (w) c is OMe; E is S or 0) Dimethyl ether . The cyanation reaction is generally carried out at 100 ~ 250 ° C, using an aprotic solvent, such as DM F, methyl-2-pyrrolidone or UMPA. Brixoline or pyridine can also be used. The formula (Ib: 8 is (^; D is Η or CN; X is H; C is 〇Me; e is S or 〇) can be converted to the relative formula (Ic: B is CN; D is Η or CN; X is Η; E is S or 0) mono- or di-aminophenol (Reaction Scheme 2), the 僳 uses quasi-demethylation method, including the use of tribromo containing more than 1 荑 equivalent Boron chloride or boron trichloride in dichloromethane, reacted at -8 ° C ~ room temperature; reacted with excess pure Bft ingot hydrochloride at 190 ~ 2 8 Q ° C; and in acetic acid Hydrobromic acid reacts at 0 ~ 50 ° C; reacts with dichloromethane, sulphur tetrachloride or acetonitrile containing excess trimethylsilyl bromide or trimethylsilyl iodide at -78 to 50 ° C; with iodine Lithium pyridine or pyridine, reversed at 100 ~ 2 5 G ° C, and more than 1 mole equivalent of ethyl, methyl or isopropyl sulfide, in the presence of 1 mole equivalent or more An acid such as lithium trichloride or boron trifluoride is reacted in a solvent such as dioxane and -7 ° C ~ 5G ° C. Formula (lb: B is I; X, D is H; C is OMe E is S or 0) Moth methyl ether derivatives or diiodo methyl ether of formula (lb: B, D is I; X is H; C is 0 Me; E ^ S or 〇) (Reaction Scheme 2) It can be reacted with more than 1 mole equivalent 'of desertified copper (I) (for monoiodide) or with more than 2 mole equivalents of odor & copper (I) reaction (for diiodide) to obtain formula (Ib: X, D is H; C is OMe; E is S or 0) monobromomethyl ether or formula (Ib., D.Br; X is H; C is OMe; E is S or 0) This Min / Iodine exchange reaction is generally carried out at 100 ~ 250 ° C, using aprotic solvents such as DMF, p-methyl-2-pyrrolidone or HMPA. This paper size can also be applied to Chinese national standards (CNS) A4 specification (210 X 297 mm) -------------------- Order --------- line (Please read the note on the back first Please fill in this page again for matters) 510900 A7 B7 V. Description of the invention (4) (Please read the notes on the back before filling this page) or pyridine. Formula (Ib: B is Br; D is Η or Br; X is H; C is OMe; E is S or 0) Mono or dibromo methoxyl can be converted to the relative formula (Ic: B is Br; D is Η or Br; X is Η; E is S or 0) Bromophenol (Reaction Scheme 2), which uses a standard demethylation method, containing more than 1 mole equivalent of dichloromethane containing boron tribromide or boron trichloride, at -7 ° C ~ Reaction at room temperature; reaction with excess pure pyridinium hydrochloride at 19 G ~ 2 0 0 ° C; reaction with hydrobromic acid in acetic acid at 0 ~ 50 ° C; and reaction with excess trimethylsilyl bromide or Trimethylsilyl iodide is reacted in dichloromethane, sulphur tetrachloride or acetonitrile at -78 ~ 50 ° C; with lithium iodide in pyridoxine or perylene, at 1GG ~ 250 ° C, And with more than 1 mole equivalent of ethyl, methyl or isopropyl sulfide, in the presence of more than 1 mole equivalent of Lewis acid such as lithium trichloride or boron trifluoride in solvents such as dichloromethane and -7 8 ° C ~ 5 D ° C.

經濟部智慧財產局員工消費合作社印製 (Ie) 反應流程3中其它式（I )化合物衍生物可依下法製得。式（Id: B，C，D為Η或OH; B，C，D組合含一以上0H; E為S或0)化合物（反應流程3)可於酚上氣原子醯化， -26- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印製 510900 A7 B7_ 五、發明說明（< ) 其像使用1莫耳當量以上適當醯化劑可得式（I d : B，C， D為H或0C0R; B, C，D組合含一以上0C0R; 1?為（：1-6烷基，芳基；E為S或0)化合物。醯化劑一般為C 烷基羧酸酐或芳基羧酸酐，或C^6烷基羧醯氯或芳基羧醯氯。使用標準方法進行反應，如使用吡啶為溶劑於含或不含共溶劑（如二氯甲烷），於〇 °C〜室溫之下反應。式（Id: B，C，D為Η或0C0R·，B，C，D組合含一以上 0C0R ; R為C卜6烷基，芳基；Ε為S或0)之醯化酚可於萘駢[2，3-b】8塞盼或萘駢[2，3-b]呋喃環上9位溴化形式（Ie: B，C，D為 Η或 0C0R; B, C，D組合含一以上 0C0R ;1?為C卜6烷基，芳基；X為Br ; Ε為S或0)之醯化溴酚 (反應流程3)。醯化反應一般使用1〜1.3莫耳當置分子溴，於黑暗下與觸媒量氯化鐵（I I I ),使用惰性溶劑，如二氯甲烷或四氯化碩，於-7 8°C〜室溫下反應。仿溴化反應，式（Id: B, D為C1〜6烷基，C為OH ; E 為S或0)酚化合物可於葉駢[2, 3-b]Bf盼或蔡駢[2，3-b] 呋喃環上9位溴化得式（Ie: B, 0為（^-8烷基，C為0H; X為Br ; E為S或0)之溴酚（反應流程3)。醯化反應一般使用1〜1 . 3莫耳當量分子溴，於黑暗下與觸媒量氯化鐵（I I I )，使用惰性溶劑，如二氯甲烷或四氯化磺，於-78°C〜室溫下反應。式（le: B，C，D為Η或0C0R; B，C，D組合含一以上 0 C 0 R ; R為Ci-6烷基，芳基；Ε為S或0)之醯化酚可使用檫準方法移除醯基可得式（Ie: B，C, D為Η或OH; B, -27- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） ------------§-------- 訂---------線 (請先閱讀背面之注意事項再填寫本頁) A7 B7 五、經濟部智慧財產局員工消費合作社印製發明說明（4 C，D組合含一以上OH ; X為Br ; E為S或〇)之溴酚（反_ 流程3)。含使用水溶液其中使用含1荑耳當量以上如 hOH之鹸金屬氫氯化物之水，與共溶劑如THF,二螬烷或Ci-s烴醇（如甲醇），或THF及Ci-6烴醇之混液，於0 °C〜4 0 °C之下反應。亦可使用酸性條件，其將化合物與1莫耳當量以上礦物酸（如HC1或硫酸 > 於水中與存在或無如THF之共溶劑，於室溫〜8fl°C下反應。式（Id: B，C, D為Η或0C0R; B, C，D組合含一以上 0C0R ;段為C卜e烷基，芳基；Ε為S或0)之醯化酿可® 化得式（Ie: B，C, D為Η或0C0R; B，C，D組合含一以上0C0R; {1為（；1-6烷基，芳基；X為Ν〇2 ; Ε為S或〇)之硝化合物（反應流程3)。於（TC〜室溫下稀釋硝酸& Λ 行此轉形反應。式（Ie: B，C，D為Η或0C0R; C，D不同為Η ; R為C卜6烷基，芳基；X為NO 2 ; Ε為S或〇)之硝化合物可再轉為式（Ie·· B，C，D為Η或0C0R; B，e， D組合含一以上0C0R; 烷基，芳基；X為科112 ’ E為S或0)之一级胺化合物，其傺使用適當還原劑如以鼦或鉑觸媒，於HC1或乙酸乙酯之二氯化錫之觸式（Ie·· B，C, D為 Η或 0C0R; B，C, D組合含一以上〇C〇R ;烷基，芳基；X為NO2或NH2 ; E為S或〇) 化合物之函基可使用標準方法移除。Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs (Ie) Other derivative compounds of formula (I) in Reaction Scheme 3 can be prepared according to the following method. Compounds of the formula (Id: B, C, D are fluorene or OH; B, C, D contains more than one OH; E is S or 0) Compound (Reaction Scheme 3) can be tritiated with gas atoms on phenol. Paper size applies Chinese National Standard (CNS) A4 specification (210 X 297 mm) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7_ V. Description of the invention (&) The agent can obtain a compound of the formula (I d: B, C, D is H or OCOR; B, C, D combination contains more than one OCOR; 1? Is (: 1-6 alkyl, aryl; E is S or 0) compounds The halogenating agent is generally a C alkyl carboxylic acid anhydride or an aryl carboxylic acid anhydride, or a C ^ 6 alkyl carboxylic acid chloride or an aryl carboxylic acid chloride. The reaction is performed using standard methods, such as using pyridine as a solvent with or without co-polymers. A solvent (such as dichloromethane) is reacted at 0 ° C to room temperature. The formula (Id: B, C, D is Η or 0C0R ·, B, C, D contains more than one 0C0R; R is C 6 Alkyl, aryl; E is S or 0) The halogenated phenol can be brominated in the 9-position on the naphthalene [2,3-b] 8 sepan or naphthalene [2,3-b] furan ring (Ie : B, C, D are Η or 0C0R; B, C, D combination contains more than one 0C0R; 1? Is C 6 alkyl Aryl; X is Br; E is S or 0) of tritiated bromophenol (Reaction Scheme 3). Tritiated reactions generally use 1 to 1.3 moles of molecular bromine in the dark with a catalytic amount of ferric chloride ( III), using an inert solvent, such as dichloromethane or tetrachloromethane, to react at -7 ° C ~ room temperature. Imitation bromination reaction, the formula (Id: B, D is C1 ~ 6 alkyl, C is OH; E is S or 0) A phenolic compound can be brominated at the 9-position on the furan ring of [2, 3-b] Bfpan or Tsai [2,3-b] to obtain the formula (Ie: B, 0 is ( ^ -8 alkyl, C is 0H; X is Br; E is S or 0) bromophenol (Reaction Scheme 3). The tritiated reaction generally uses 1 to 1.3 molar equivalents of molecular bromine. Medium iron (III) chloride, using an inert solvent, such as dichloromethane or sulphur tetrachloride, to react at -78 ° C ~ room temperature. Formula (le: B, C, D is Η or 0COR; B, C, D combination contains more than one 0 C 0 R; R is Ci-6 alkyl, aryl; E is S or 0) the halogenated phenol can be removed by standard methods to obtain the formula (Ie: B, C, D are Η or OH; B, -27- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ------------ § ----- --- Order --------- line (please Read the notes on the reverse side and fill in this page) A7 B7 V. Bromophenol printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs (4 C, D combination contains more than one OH; X is Br; E is S or 〇) (Anti_Process 3). Contains an aqueous solution in which water containing more than 1 荑 equivalent of rhenium metal hydrochloride such as hOH, and a co-solvent such as THF, dioxane or Ci-s hydrocarbon alcohol (such as methanol), or THF and Ci-6 hydrocarbon alcohol The mixture was reacted at 0 ° C ~ 40 ° C. Acidic conditions can also be used, which react the compound with a mineral acid of more than 1 mole equivalent (such as HC1 or sulfuric acid) in water with a co-solvent with or without THF at room temperature to 8 fl ° C. Formula (Id: B, C, D is fluorene or 0C0R; B, C, D combination contains more than one OC0R; segment is C alkyl group, aryl group; E is S or 0) can be converted into formula (Ie: B, C, D is fluorene or 0C0R; B, C, D combination contains more than one 0C0R; {1 is (; 1-6 alkyl, aryl; X is NO2; E is S or 〇) nitrate compounds (Reaction Scheme 3). Dilute the nitric acid & Λ to perform this transformation reaction at (TC ~ room temperature. Formula (Ie: B, C, D is Η or 0C0R; C, D is different from Η; R is C 6) Alkyl, aryl; X is NO 2; E is S or O) nitrate compounds can be converted to formula (Ie · · B, C, D is Η or 0C0R; B, e, D combination contains more than one 0C0R; Alkyl group, aryl group; X is a first-class amine compound of 112 'E is S or 0), and its contact with tin dichloride of HC1 or ethyl acetate using a suitable reducing agent such as rhenium or platinum catalyst Formula (Ie ·· B, C, D is Η or 0COR; B, C, D combination contains more than one OCOR; alkyl, aryl; X is NO2 or NH2; E Functional group S or square) of the compound may be removed using standard methods.

式（Ie: B，C，D為Η或0C0R; B, C，D組合含一以上 0C0R; R為“^烷基，芳基；X為Br; Ε為S或〇)之酿化溴酚（反應流程3)可轉為式（Ie: B，C, D為Η或〇c〇R -28- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） ------------壤------- 丨訂---------線· (請先間讀背面之注意事項再填寫本頁) 510900 A7 B7 五、發明說明（w) (請先閱讀背面之注意事項再填寫本頁) ;B，C，D組合含一以上OCOR; {{為^^烷基，芳基；X 為CN ; E為S或0)之醯化氰酚，其偽由與1莫耳當量以上氡化銅（I)反應而得。氰化反應一般於1 〇〇〜2 5 0 °C下進行，使用非質子溶劑，如D M F，卜甲基-2 - Hft咯啶酮或 HMPA。亦可使用賭啉或吡啶。式（Ie: B, C，D為Η或 0C0R ; B, C, D組合含一以上0C0R; R為Cp6烷基，芳基；X為Br ; E為S或0)之醯基可於氰化反應下去除而得式（Ie: B，C，D為Η或OH ; B, C, D組合含一以上OH ; X 為CN; Ε為S或0)之氰酚。去除醯基而得式（Ie:B, C, D為Η或OH; B，C, D組合含一以上OH; X為CN; E為S或0) 氰酚之反應可由將含1莫耳當量以上鹸金屬氫氯化物之水，加至含式（I e : B , C，D為Η或0C0R ; B，C，D組合含一以上0C0R; R為Ci-e烷基，芳基；X為CN; Ε為S或0) 中。醯基亦可由單離式（Ie: B，C, D為Η或0C0R; Β, C, D組合含一以上0C0R; 烷基，芳基；X為經濟部智慧財產局員工消費合作社印製 C N ; E為S或0)之醯化氰酚依標準方法去除而得式（I e : B，C，D為Η或OH; B，C，D組合含一以上OH; R為Ci-6 烷基，芳基；X為Cfi ; E為S或0)。含使用水溶液其中使用含1莫耳當量以上如NaOH之鹼金屬氫氣化物之水，與共溶劑如THF，二鸣烷或低烴醇（如甲醇），或THF及低烴醇之混液，於〇 °C〜4 0°C之下反應。亦可使用酸性條件，其將化合物輿1莫耳當量以上礦物酸（如HC1或硫酸）於水中與存在或無如THF之共溶劑，於室溫〜80°C下反 -29- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印製 510900 A7 B7 發明說明（j) 式（Id: B，C，D為Η或OH; B，C，D組合含一以上OH; E為S或0)化合物（反應流程3)可將酚之氣原子磺醯化，其偽使用1莫耳當量以上適當磺_劑可得式（Id: B， C，D為Η或OS〇2 R; B， C，D組合含一以上OSO2 R; R為 Ci- 6烷基，芳基；Ε為S或0)磺酸酯。磺醯剛一般為 Ci-e烷基磺酸酐或芳基磺酸酧，-Cks烷基磺醯氯或芳基磺醯氯。依檫準方法使用如毗啶為溶劑，於存在或無如二氯甲烷之共溶劑下，於fl°C〜室溫之下反應。式（Id: B，C，D為 Η或 OSO2R; B，C, D組合含一以上0S02 R;较為^^烷基，芳基；E為S或0)磺酸酯可處理以碘化麵，於養駢[2，3 - b】晴吩或#駢[2，3 - b ]呋喃環上9位碘化得式（I e : B，C，D為Η或0 S 0 2 R ; B , C，D 組合含一以上0S0 2 R ; R為C 1〜6烷基，芳基·，X為I ; Ε為 S或0)之碘磺酸酯。適當碘化劑含0.7莫耳當量以上碘與0.25莫耳當量以上碘酸於THF及80%乙酸，其含少量濃硫酸，於室溫〜80°C下反應。由式（Ie: B，C, D為Η或 0 S 0 2 R ； B , C，D組合含一以上0S02R;R為C1〜6烷基，芳基；X為I E為S或0)碘磺酸酯可依標準方法移除磺酸酯而得式（le: B，C，D為Η或OH ; B，C, D組合含一以上OH ; X為I ; Ε為S或0)碘酚（反應流程3)。含使用水溶液其中使用含1莫耳當量以上如Na〇H之鹼金屬氫氣化物之水，與共溶劑如T H F，二鸣烷或低烴酵（如甲醇），或T H F及低烴醇之混液，於室溫〜1 1 0 °C之下反應。 -30- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) -I i_li Λ/mmm ϋ 1_ϋ ·ϋ ·ϋ Mmmmmm an 1 峙口線·(Ie: B, C, D is Η or OCOR; B, C, D combination contains more than one OCOR; R is "^ alkyl, aryl; X is Br; Ε is S or 〇) (Reaction scheme 3) can be transformed into formula (Ie: B, C, D is Η or 〇c〇R -28- This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) ---- -------- Soil ------- 丨 Order --------- Line · (Please read the precautions on the back before filling this page) 510900 A7 B7 V. Description of the invention (W) (Please read the notes on the back before filling this page); B, C, D combination contains more than one OCOR; {{is ^^ alkyl, aryl; X is CN; E is S or 0) Tritiated cyanophenol, which is obtained by reacting with copper (I) trioxide above 1 mole equivalent. The cyanidation reaction is generally carried out at 100 ~ 250 ° C, using an aprotic solvent such as DMF, methyl -2-Hft-pyrrolidone or HMPA. Glypholine or pyridine can also be used. Formula (Ie: B, C, D is fluorene or 0C0R; B, C, D combination contains more than one 0C0R; R is Cp6 alkyl, aromatic X is Br; E is S or 0) The fluorenyl group can be removed under cyanation reaction to obtain the formula (Ie: B, C, D is fluorene or OH; B, C, D combination contains more than one OH; X Is CN; Ε is S 0) cyanophenol. Removal of the fluorene group to obtain the formula (Ie: B, C, D is fluorene or OH; B, C, D combination contains more than one OH; X is CN; E is S or 0) Reaction of cyanophenol Can be added to the water containing more than 1 mole equivalent of rhenium metal hydrochloride to the formula (I e: B, C, D is Η or 0C0R; B, C, D combination contains more than one 0C0R; R is Ci-e Alkyl, aryl; X is CN; E is S or 0). The fluorenyl group can also be a single ion (Ie: B, C, D is fluorene or 0C0R; Β, C, D combination contains more than one 0C0R; alkane Base, aryl; X is printed by CN of the Employees' Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs; E is S or 0) The tritiated cyanophenol is removed by standard methods (I e: B, C, D is Η or OH B, C, D combination contains more than one OH; R is Ci-6 alkyl, aryl; X is Cfi; E is S or 0). Contains the use of aqueous solution which contains more than 1 mole equivalent of alkali metal such as NaOH Hydrogenated water reacts with a co-solvent such as THF, dioxane or a lower hydrocarbon alcohol (such as methanol), or a mixture of THF and a lower hydrocarbon alcohol at 0 ° C ~ 40 ° C. Acidic conditions can also be used , It will compound compounds with more than 1 mole equivalent of mineral acid (such as HC1 or sulfuric acid) in water with or without THF. Solvent, anti--29 at room temperature ~ 80 ° C- This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7 Invention Description (j ) Formula (Id: B, C, D is Η or OH; B, C, D combination contains more than one OH; E is S or 0) Compound (Reaction Scheme 3) can sulfonate phenol gas atom, its pseudo The formula (Id: B, C, D is fluorene or OS〇2 R; B, C, D contains more than one OSO2 R; R is Ci-6 alkyl, aromatic E; S is S or O) sulfonate. Sulfonamide is generally Ci-e alkylsulfonic anhydride or arylsulfonium sulfonium, -Cks alkylsulfonyl chloride or arylsulfonyl chloride. According to the standard method, use pyridine as a solvent, and react in the presence or absence of a co-solvent such as dichloromethane at fl ° C ~ room temperature. Formula (Id: B, C, D is Η or OSO2R; B, C, D combination contains more than one OS02 R; more ^ alkyl, aryl; E is S or 0) sulfonate can be treated to iodinate Surface, in yangyang [2,3-b] clear phen or # 骈 [2,3-b] iodination of the 9-position on the furan ring to obtain the formula (I e: B, C, D is Η or 0 S 0 2 R B, C, D combination contains more than one 0S0 2 R; R is a C 1-6 alkyl group, aryl ·, X is I; E is S or 0) iodine sulfonate. A suitable iodinating agent contains 0.7 mol equivalent or more of iodine and 0.25 mol equivalent or more of iodic acid in THF and 80% acetic acid. It contains a small amount of concentrated sulfuric acid and reacts at room temperature to 80 ° C. From the formula (Ie: B, C, D is Η or 0 S 0 2 R; B, C, D combination contains more than one OS02R; R is C1 ~ 6 alkyl, aryl; X is IE is S or 0) iodine The sulfonate can be removed by standard methods to obtain the formula (le: B, C, D is hydrazone or OH; B, C, D combination contains more than one OH; X is I; E is S or 0) iodine Phenol (Reaction Scheme 3). Contains the use of an aqueous solution in which water containing more than 1 mol equivalent of an alkali metal hydride such as NaOH is mixed with a co-solvent such as THF, dioxane or a low-hydrocarbon enzyme (such as methanol), or a mixture of THF and a low-carbon alcohol, React at room temperature to 110 ° C. -30- This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) (Please read the notes on the back before filling in this page) -I i_li Λ / mmm ϋ 1_ϋ · ϋ · ϋ Mmmmmm an 1峙口线 ·

510900 A7 B7 五、發明說明（w)510900 A7 B7 V. Description of the invention (w)

式（If: C，D為Η或OSO2R; c，D不同為Η;兄為“-e 烷基，芳基；E為S或0)之碘磺酸酯可為反應流程4中其它式（I)化合物衍生物之原料並侬下法製得。將式（I f :C，D為Η或0S02R;C，D不同為Η·，ϋ為C卜6烷基，芳基；Ε為S或0)化合物與試劑反應催化（If)中碘原子與低全氟烷基交換而得式（Ig: C，D為Η或0S02R; C， D不同為Η ; R為C ^ 6烷基，芳基；X為低全氟烷基；E為 S或0 )(反應流程4 )。互換反應之試劑及條件含將（I f ) 於無水下與1〜10莫耳當量之全氟羧酸鈉（RC02Na:R 為全氟烷基）及1〜5莫耳當量之碘化銅（I),於高沸點惰性溶劑，如DMF，DM A或卜甲基-2-吡咯啶酮，於140 〜2 0 0 °C下反應。此外，式（I g ·· C，D為Η或0S0 2 R ; C , I)不同為H; R為烷基，芳基；X為低全氟烷基；Ε為 S或0)化合物亦可由式（If: C, D為Η或OS〇2li; C，D不同為Η ; R為C 烷基，芳基；E為S或0)之化合物製得，將前者與1〜10莫耳當量之全氟烷碘及1〜5莫耳當量 -31- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 ^1^· (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製經濟部智慧財產局員工消費合作社印製 510900 A7 B7 五、發明說明（V) 活化Cu°，於高沸點惰性溶劑，如DMF，DMA或卜甲基- 2-吡咯啶酮，於1 4 0〜2 0 0 °C下反應。此外，式（I f ·· C，D 為Η或OS〇2 R; C，D不同為H; R為Ci-e烷基，芳基；E 為S或0)之化合物亦可處理以0.5〜2莫耳當量雙（三氟甲基）汞及2〜4莫耳當量活化Cii Q，於高沸點惰性溶劑，如D M F，1) Μ A或1 -甲基-2 - Bft咯啶酮，於1 4 0〜2 0 0 °C下反應可得式（Ig: C，D為Η或0S02R; C，D不同為H; R 為Ci-6烷基，芳基；X為CF3 ; E為S或0)化合物。式（Ig: C， D為 Η或 OSO2R; C, D不同為 H; R為 Ci-e 烷基，芳基；X為烷基；E為S或0)化合物（反應流程4)之9-烷基衍生物可由式（If: C，D為Η或0S02R ;C, D不同為H; R為Ci-e烷基，芳基；E為S或0)與3 莫耳當量以上之低四烷錫，於存在鉑觸媒（如1〜10奠耳％雙（三苯_)氯化鉑II,於如DMF，DMA或卜甲基-2-吡咯啶麵之適當溶劑，於1 4 0〜2 0 0 °C下反應製得。磺醯_可再由式（Ig: C，D為Η或0S02R; C，D不同為R為C1-6烷基，芳基·，X為烷基或低全氟烷基；E為S或0)磺酸酯依標準方法除去而得式（Ig: C， D為Η或0S02 R; C，D不同為Η; X為Ci-s烷基或低全氟烷基；E為S或0)酞。含使用水溶液其中使用含1莫耳當量以上如NaOH之鹼金屬氫氧化物之水，與共溶_如1^? ，二鸣烷或低烴醇（如甲醇），或THF及低烴醇之混液，於室溫〜1 1 0 °C之下反應。式（Ig·· C，D為Η或OH; C，D不同為H; R為Ci-e烷氣 -3 2 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線·· (請先閱讀背面之注意事項再填寫本頁) 510900 Α7 Β7 經濟部智慧財產局員工消費合作社印製五、發明說明（y) 基；E為S或0)化合物之9-烷氣衍生物可由式（If ·· C, D為Η或OSO2 R; C，I)不同為Η;段為“”烷基，芳基； Ε為S或0)與3莫耳當量以上之低鹼金屬烷氣化物，如甲氧化鈉，於存在銅（I)或銅（I I)觸媒，如1〜1 〇莫耳％氯化銅（II)於如DMF，DMA或1-甲基咯啶酮之適當溶劑，於80〜18fl°C下反應製得。由此反應，可除去式（If: C， D為Η或0S02R;C， D不同為H;R為烷基，芳基；E為S或0)之磺酸基。式（Ig·· C，D為Η或OH; C，D不同為H;义為“·^烷基，磺_基，芳磺醯基，_啶磺醱基，2-Ν，Ν -二甲胺乙磺醯基；Ε為S或0)化合物之9-磺醒基化衍生物可由式 ί If: C，I)為 Η或 OS〇2R;C，D 不同為 H;R為烷基，芳基；E為S或0)與1奠耳當量以上之適當C 6烷硫醇，芳硫醇，硫吡啶或2-N，N -二甲胺乙硫氫，1莫耳當量以上之如HaO Η之鹼金屬氫氣化物，1莫耳當量以上銅 (I)或銅（II)觸媒，如氧化銅（I)於如DMF，DM Α或卜甲基-2-Pft咯啶國之適當溶劑，於100〜180 °C下反應製得。由此反應，可除去式（If : C, D為Η或0S02R ; C， D不同為H; R為C1〜6烷基，芳基；Ε為S或0)之磺酸基。 -33- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） -------------fi — (請先閱讀背面之注意事項再填寫本頁) 訂----------線| 經濟部智慧財產局員工消費合作社印製 510900 A7 B7 五、發明說明（w)The iodosulfonate of formula (If: C, D is Η or OSO2R; c, D is different from Η; brother is "-e alkyl, aryl; E is S or 0) can be other formulas in reaction scheme 4 ( I) The raw material of the compound derivative is prepared by the following method. The formula (I f: C, D is Η or OS02R; C and D are different from Η, ϋ is C 6 alkyl, aryl; E is S or 0) The reaction between the compound and the reagent catalyzes (If) the iodine atom and the lower perfluoroalkyl group to exchange to obtain the formula (Ig: C, D is Η or OS02R; C, D is different from Η; R is C ^ 6 alkyl, aromatic X is a low perfluoroalkyl group; E is S or 0) (reaction scheme 4). Reagents and conditions for the interchange reaction include (I f) under water-free and 1 to 10 mole equivalents of sodium perfluorocarboxylate (RC02Na: R is a perfluoroalkyl group) and 1 ~ 5 mol equivalent of copper (I) iodide, in a high boiling point inert solvent, such as DMF, DM A or methyl-2-pyrrolidone, at 140 ~ 2 0 Reaction at 0 ° C. In addition, the formula (I g ·· C, D is 0 or OS0 2 R; C, I) is different from H; R is alkyl, aryl; X is low perfluoroalkyl; E is S or 0) compounds can also be prepared from compounds of the formula (If: C, D is Η or OS〇2li; C, D is different from Η; R is C alkyl, aryl; E is S or 0) , The former with 1 to 10 mol equivalent of perfluoroalkane iodine and 1 to 5 mol equivalent -31- This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) ------ -------------- Order --------- line ^ 1 ^ · (Please read the notes on the back before filling out this page) Employees ’Cooperatives, Intellectual Property Bureau, Ministry of Economic Affairs Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, printed 510900 A7 B7 V. Description of the invention (V) Activated Cu °, in a high boiling point inert solvent, such as DMF, DMA or p-methyl-2-pyrrolidone, at 1 4 0 ~ 2 0 0 ° C. In addition, the formula (I f ·· C, D is Η or OS〇 2 R; C, D is different from H; R is Ci-e alkyl, aryl; E is S or 0 ) Compounds can also be treated with 0.5 ~ 2 mole equivalents of bis (trifluoromethyl) mercury and 2 ~ 4 mole equivalents of activated Cii Q in high boiling point inert solvents such as DMF, 1) M A or 1-methyl -2-Bft pyridone, reacted at 1 40 ~ 2 0 ° C to obtain the formula (Ig: C, D is Η or OS02R; C, D is different from H; R is Ci-6 alkyl, aromatic X is CF3; E is S or 0) compounds. Formula (Ig: C, D is Η or OSO2R; C, D is different from H; R is Ci-e alkyl, aromatic X is alkyl; E is S or 0) The 9-alkyl derivative of the compound (Reaction Scheme 4) can be represented by the formula (If: C, D is Η or OS02R; C, D is different from H; R is Ci-e Alkyl, aryl; E is S or 0) and lower tetraalkanetin with 3 mol equivalent or more, in the presence of a platinum catalyst (such as 1 to 10 mol% bis (triphenyl_) platinum chloride II, such as DMF, DMA or a suitable solvent for the methyl-2-pyrrolidine surface, prepared by the reaction at 140 ~ 200 ° C. Sulfonium_ can be further represented by the formula (Ig: C, D is fluorene or OS02R; C and D are different, R is C1-6 alkyl, aryl, X is alkyl or lower perfluoroalkyl; E is S or 0) The sulfonic acid ester is removed according to standard methods to obtain the formula (Ig: C, D is Η or OS02 R; C, D is different from Η; X is Ci-s alkyl or lower perfluoroalkyl; E is S or 0 ) Phthalein. Contains the use of an aqueous solution in which water containing more than 1 mol equivalent of an alkali metal hydroxide such as NaOH is co-soluble with 1 ^ ?, dioxane or a lower hydrocarbon alcohol (such as methanol), or THF and a lower hydrocarbon alcohol. Mix and react at room temperature to 110 ° C. Formula (Ig ·· C, D is Η or OH; C, D is different from H; R is Ci-e alkane-3 2-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) -------------------- Order --------- Line ·· (Please read the precautions on the back before filling this page) 510900 Α7 Β7 Economy Printed by the Consumer Cooperatives of the Ministry of Intellectual Property Bureau 5. The invention description (y) group; E is S or 0) The 9-alkane derivative of the compound can be represented by the formula (If ·· C, D is Η or OSO2 R; C, I ) Is different from Η; the segment is "" alkyl group, aryl group; E is S or 0) and a low alkali metal alkane gaseous substance such as sodium methoxide in the presence of copper (I) or copper (II) ) Catalysts, such as 1 ~ 10 mole% copper (II) chloride in a suitable solvent such as DMF, DMA or 1-methylpyridone, are prepared by reaction at 80 ~ 18fl ° C. By this reaction, the sulfonic acid group of the formula (If: C, D is fluorene or OS02R; C and D are different from H; R is alkyl, aryl; E is S or 0) can be removed. Formula (Ig ·· C, D is Η or OH; C, D is different from H; meaning "· ^ alkyl, sulfo_, arylsulfonyl, _pyridylsulfonyl, 2-N, N -di Methylamine ethylsulfonyl group; E is S or 0) 9-sulfonylated derivatives of compounds can be represented by the formula: If: C, I) is fluorene or OS〇2R; C, D are different H; R is alkyl Aryl; E is S or 0) and appropriate C 6 alkanethiol, aryl mercaptan, thiopyridine or 2-N, N-dimethylamine ethyl sulfide, 1 mol equivalent or more Such as HaO Η alkali metal hydride, more than 1 mole equivalent of copper (I) or copper (II) catalysts, such as copper (I) oxide in the appropriate solvents such as DMF, DM A or methyl-2-Pft pyridine , Prepared by reaction at 100 ~ 180 ° C. From this reaction, the formula (If: C, D is fluorene or OS02R; C, D is different from H; R is C1 ~ 6 alkyl, aryl; E is S or 0) sulfonic acid group. -33- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ------------- fi — (Please read first Note on the back, please fill in this page again) Order ---------- Line | Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7 V. Description of Invention (w)

反應流程5中其它式（I)化合物衍生物可依下法製得。式（Ih:A為Η或OH; X為H，鹵素，Ci-e烷基，CN，低全氟烷基，Ci_e烷氣基，芳烷氣基，硝基，Ci-6烷磺醯基，芳磺醯基，吡啶磺_基，2-N，N -二甲胺乙磺醯基；E為S或0 )化合物可於2個位置溴化而得式（I i : A為 OH ; B，D為Br; X為Η,鹵素，Cu烷基，CN,低全氟烷基，Ch6烷氣基，芳烷氣基，硝基，Ci-6烷磺醯基，芳磺醒基，％啶磺醯基，2-N，N-二甲胺乙磺醯基； E為S或0)二溴酚，其使用2莫耳當量以上分子溴，於如乙酸之適當溶劑下進行。亦可使用1〜15莫耳當量之乙酸鹽，如乙酸鉀或乙酸銷，作為共試劑，但其並非必霈試劑。式（Ih : A為Η ; X為Η，鹵素，C ；l-6烷基，CN，低全氟烷基，烷氧基，芳烷氯基，硝基，Cb8烷磺醯基，芳磺醯基，峨啶磺醯基，2-N，N -二甲胺乙磺爾基；E 為S或0)酚可使用三硝化鐵（III)，於低醇溶劑下單 -34- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7 五、發明說明（w) 硝化為式（Ii:A為Η ; B為NO 2 ; D為Η ; X為H，鹵素，Derivatives of other compounds of formula (I) in Reaction Scheme 5 can be prepared by the following method. Formula (Ih: A is fluorene or OH; X is H, halogen, Ci-e alkyl, CN, lower perfluoroalkyl, Ci_e alkyl, aralkyl, nitro, Ci-6 alkylsulfonyl , Arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; E is S or 0) The compound can be brominated at 2 positions to obtain the formula (I i: A is OH; B, D is Br; X is fluorene, halogen, Cu alkyl, CN, lower perfluoroalkyl, Ch6 alkylamino, aralkylamino, nitro, Ci-6 alkylsulfonyl, arylsulfonyl, % Pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; E is S or 0) dibromophenol, which is performed using a molecular bromine of more than 2 mole equivalents in a suitable solvent such as acetic acid. It is also possible to use 1 to 15 molar equivalents of acetic acid, such as potassium acetate or sodium acetate, as co-reagents, but this is not a necessary reagent. Formula (Ih: A is Η; X is Η, halogen, C; 1-6 alkyl, CN, lower perfluoroalkyl, alkoxy, aralkylchloro, nitro, Cb8 alkylsulfonyl, arylsulfonyl Fluorenyl, eridinesulfonyl, 2-N, N-dimethylamine ethanesulfenyl; E is S or 0) Phenol can use iron (III) trinitrate in low alcohol solvent -34- Standards apply to China National Standard (CNS) A4 specifications (210 X 297 mm) -------------------- Order --------- line (please Read the notes on the back before filling out this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economy 510900 A7 B7 V. Description of the invention (w) Nitrification is formula (Ii: A is Η; B is NO 2; D is Η; X is H, halogen,

Ci-6烷基，CN,低過氟烷基，Ci-8烷氣基，芳烷氣基，硝基，Ci-e烷磺醯基，芳磺醯基，Bft啶磺醯基，2-N ,N -二甲胺乙磺醯基；E為S或0)酚。式（Ii:A 為 Η; B 為 N〇2 ； D為 Η ; X為 Η，_素，C 卜 6 烷基，CN，低全氟烷基，C&6烷氧基，芳烷氣基，硝基，Ci-e烷磺醯基，芳磺醯基，Bft啶磺醯基，2-Ν，Ν-二甲胺乙磺醯基；E為S或0)硝化合物可還原為式（Ii:A 為Η; B為NH2 ; D為Η; X為H，鹵素，Ci-6烷基，CN，低全氟烷基，Ci-6烷氧基，芳烷氣基，硝基，烷磺_基，芳磺醯基，吡啶磺醱基，2-N，N-二甲胺乙磺醯基；E為S或0)胺化合物，其傺使用二氯化錫於乙酸乙酯，於4 0〜1 0 0 °C下反應製得，或與於乙醇之阱及蒙脫土，於4 0〜1 G 0°C下反應製得。式（li: A為Η ; B為N0 2 ; D為Η ; X為H，齒素，C卜6 烷基，CN，低全氟烷基，烷氣基，芳烷氣基，硝基，Ci-e烷磺醯基，芳磺醯基，毗啶磺醯基，2_N，N-二甲胺乙磺醯基；E為S或0)硝化合物亦可溴化為式 (Ii:A為 Η; B為 N〇2 ; D為 Br; X為 H，鹵素，Cljfce 烷基，CN，低全氟院基，Ci-6焼氧基，芳院氣基，硝基， Ci-6烷磺醯基，芳磺醯基，吡啶磺醯基，2-N，N-二甲胺乙磺醯基；E為S或0)化合物，其偽使用2奠耳當量以上分子溴，於如乙酸之適當溶劑下進行。亦可使用1〜1 5 莫耳當量之乙酸鹽，如乙酸鉀或乙酸鈉，作為共試劑， -35- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 _B7___ 五、發明說明（Μ ) 但其並非必需試劑。此式（I i : A為Η ; B為NO 2 ; D為Br ; X為H，鹵素，Ci-6烷基，CN,低全氟烷基，Cps烷氣基，芳烷氧基，硝基，6烷磺醯基，芳磺醯基，m 啶磺醯基，2-N，N-二甲胺乙磺醯基；E為S或0)溴化硝化合物亦可還原為式（I i : A為Η ·，B為NH2 ; D為Br ; X為 H，齒素，Ci-6烷基，CN，低全氟烷基，Cp6烷氣基，芳烷氧基，胺基，Ci-6烷磺醯基，芳磺醯基，毗啶磺醯基，2 - N，N -二甲胺乙磺醯基；E為S或0 )溴胺化合物，傺使用二氯化錫於乙酸乙酯，於4 0〜1 0 0 °C下反應製得，或與於乙醇之阱及蒙脱土，於4 0〜1 0 0°C下反應製得。式（I i : A為Η ; B為NH 2 ; D為Η或Br ; X為Η，鹵素，Ci-6 alkyl, CN, lower perfluoroalkyl, Ci-8 alkyl, aralkyl, nitro, Ci-e alkylsulfonyl, arylsulfonyl, Bft pyridylsulfonyl, 2- N, N-dimethylamineethanesulfonyl; E is S or O) phenol. Formula (Ii: A is Η; B is No 2; D is Η; X is Η, _ prime, C 6 alkyl, CN, lower perfluoroalkyl, C & 6 alkoxy, aralkyl gas group , Nitro, Ci-e alkylsulfonyl, arylsulfonyl, Bft pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; E is S or 0) Nitric compounds can be reduced to the formula ( Ii: A is Η; B is NH2; D is Η; X is H, halogen, Ci-6 alkyl, CN, lower perfluoroalkyl, Ci-6 alkoxy, aralkylamino, nitro, alkane Sulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; E is S or O) amine compound, using tin dichloride in ethyl acetate, and It is prepared by reacting at 40 ~ 100 ° C, or by reacting with ethanol well and montmorillonite at 40 ~ 1G 0 ° C. Formula (li: A is Η; B is N0 2; D is Η; X is H, dentin, C 6 alkyl, CN, lower perfluoroalkyl, alkane, aralkyl, nitro, Ci-e alkylsulfonyl, arylsulfonyl, pyridinsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; E is S or 0) Nitric compounds can also be brominated to formula (Ii: A is Η; B is No2; D is Br; X is H, halogen, Cljfce alkyl, CN, low perfluorinated radical, Ci-6fluorenyloxy, aromatic radical, nitro, Ci-6 alkylsulfonate Fluorenyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; E is S or O) compound, which pseudo-uses more than 2 mole equivalents of molecular bromine, such as acetic acid Performed in a suitable solvent. It is also possible to use 1 ~ 1 5 mol equivalents of acetate, such as potassium acetate or sodium acetate, as a co-reagent. -35- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) --- ----------------- Order --------- line (please read the notes on the back before filling out this page) Manufacturing 510900 A7 _B7___ 5. Description of the Invention (M) But it is not a necessary reagent. This formula (I i: A is Η; B is NO 2; D is Br; X is H, halogen, Ci-6 alkyl, CN, lower perfluoroalkyl, Cps alkanoyl, aralkoxy, nitrate Group, 6-alkanesulfonyl, arylsulfonyl, m-pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; E is S or 0) The nitrated bromide compound can also be reduced to the formula (I i: A is Η ·, B is NH2; D is Br; X is H, dentin, Ci-6 alkyl, CN, lower perfluoroalkyl, Cp6 alkanoyl, aralkoxy, amine, Ci -6 alkylsulfonyl, arylsulfonyl, pyridinsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; E is S or 0) bromoamine compound, tin dichloride is used in acetic acid Ethyl esters are prepared by reacting at 40 ~ 100 ° C, or by reacting with ethanol trap and montmorillonite at 40 ~ 100 ° C. Formula (I i: A is Η; B is NH 2; D is Η or Br; X is Η, halogen,

Ci-6烷基，CN，低全氟烷基，C^6烷氣基，芳烷氣基，胺基，烷磺醯基，芳磺醯基，Bft啶磺醯基，2-N ，卜二甲胺乙磺醯基；E為S或0)胺化合物可醯化以一以上當量式（LG) C〇2Rla或（LG)COR la 之適當醯化劑 (式中LG為如C1之醒鹵或氯甲酸鹽離去基或為0C0Rla_ 0 C0 2 Rla作為酧或混合酐離去基等；烷基，芳烷基及芳基）而得式（Ii:A為Η; B為NHC0Rla_ NH2C〇2Rla;D為Η或Br;X為H，鹵素，C卜6烷基，CN ，低全氟烷基，Ci-6烷氧基，芳烷氯基，胺基，Cn 烷磺醯基，芳磺薦基，P«i啶磺醯基，2-N，N-二甲胺乙磺醯基；E為S或0;烷基，芳烷基及芳基）。此_化可於存在1莫耳當量以上適當鹼，如鹼金屬氫 -36- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線% (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7 五、發明說明（V) 氣化物，磺酸鹽或重磺酸鹽，或有機胺如三乙胺或％淀，於存在或無適當溶劑，如氯仿，二氯甲烷，THF,二鸣烷及水或其混液，於存在或無觸媒如4 - S，N -二甲Pft 啶下進行。式（I i : A為OH ; B，D為Br ; X為Η ; E為S或0)可再於於萘駢[2，3-b]l«盼或萘駢[2，3-b]呋喃環上9位溴化得式（I i : A為OH ; B , D，X為Br ; E為S或0)之雙酚。溴化反應一般使用1〜1 . 3莫耳當量分子溴，於黑暗下與觸媒量氯化鐵（I I I )，使用惰性溶劑，如二氯甲烷或四氯化磺，於-7 8 °C〜室溫下反應。砭瞧流稃βCi-6 alkyl, CN, lower perfluoroalkyl, C ^ 6 alkylamino, aralkylamino, amine, alkanesulfonyl, arylsulfonyl, Bft pyridylsulfonyl, 2-N, Bu Dimethylamine ethylsulfonyl group; E is S or O) The amine compound can be converted with more than one equivalent of an appropriate ammonium formula (LG) C02Rla or (LG) COR la (wherein LG is the Halogen or chloroformate leaving group or 0C0Rla_ 0 C0 2 Rla as fluorene or mixed anhydride leaving group, etc .; alkyl, aralkyl and aryl) to obtain formula (Ii: A is Η; B is NHC0Rla_ NH2C 〇2Rla; D is fluorene or Br; X is H, halogen, C6 alkyl, CN, lower perfluoroalkyl, Ci-6 alkoxy, aralkyl chloride, amine, Cn alkylsulfonyl, Arosulfamoyl, P «ipyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; E is S or 0; alkyl, aralkyl and aryl). This chemical can be in the presence of a suitable alkali above 1 mol equivalent, such as alkali metal hydrogen -36- This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) ---------- ---------- Order --------- Line% (Please read the notes on the back before filling out this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7 V. Description of the Invention (V) Gases, sulfonates or disulfonates, or organic amines such as triethylamine or hydrate, in the presence or absence of a suitable solvent such as chloroform, dichloromethane, THF, dioxane and water or The mixed solution is carried out in the presence or absence of a catalyst such as 4 -S, N -dimethyl Pft. The formula (I i: A is OH; B, D is Br; X is Η; E is S or 0) may be replaced by naphthalene [2,3-b] l or naphthalene [2,3-b] The bromine at position 9 on the furan ring gives a bisphenol of the formula (I i: A is OH; B, D, X is Br; E is S or 0). The bromination reaction generally uses 1 to 1.3 molar equivalents of molecular bromine, in the dark with a catalytic amount of iron (III) chloride, using an inert solvent such as dichloromethane or sulfonic tetrachloride, at -78 ° C ~ React at room temperature.砭流流稃 β

反應流程6中其它式（I)化合物衍生物可依下法製得。式（Ij:C為H; D為OH; X為鹵素，Ci-6烷基，CN，低全氟烷基，Ci-6烷氧基，芳烷氯基，硝基，6烷磺醯基，芳磺醯基，毗啶磺醯基，2-N，N-二甲胺乙磺醯基；E為S或0)酚可單溴化而得式（I k : A，B為Η ; C為 Br;D為0Η;Χ為_素，Ci-6烷基，CN，低全氟烷基， -37- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7_ 五、發明說明（4 )The derivatives of other compounds of formula (I) in Reaction Scheme 6 can be prepared by the following method. Formula (Ij: C is H; D is OH; X is halogen, Ci-6 alkyl, CN, lower perfluoroalkyl, Ci-6 alkoxy, aralkyl chloride, nitro, 6 alkylsulfonyl , Arylsulfonyl, pyridinsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; E is S or 0) phenol can be monobrominated to obtain formula (I k: A, B is ，; C is Br; D is 0Η; X is _ prime, Ci-6 alkyl, CN, low perfluoroalkyl, -37- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm)- ------------------- Order --------- line (please read the precautions on the back before filling this page) Staff Consumption of Intellectual Property Bureau of the Ministry of Economic Affairs Printed by the cooperative 510900 A7 B7_ V. Description of the invention (4)

Cl- 8焼氧基，芳続氣基，硝基，Cl-8院磺醯基，芳磺醯基，毗啶磺醱基，2 - N，N -二甲胺乙磺醯基；E為S或0 ) 溴酚，其使用1莫耳當量以上分子溴，於如乙酸之適當溶劑下進行，或二溴化而得式（I k : B為Η ; A，C為Br ; D為011;乂為_素，Cte烷基，CN，低全氟烷基，Cn 烷氣基，芳烷氧基，硝基，C 烷磺醯基，芳磺醯基，毗啶磺醒基，2-N，N -二甲胺乙磺醯基；E為S或0)溴酚，其使用2莫耳當量以上分子溴，於如乙酸之適當溶劑下進行。相似地，式（Ij : C，D為OH ; X為鹵素，Cl-8 methoxy, aryl fluorenyl, nitro, Cl-8 sulfonyl, arylsulfonyl, pyridinylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; E is S or 0) bromophenol, which uses more than 1 mole equivalent of molecular bromine, is performed in a suitable solvent such as acetic acid, or is dibromated to obtain formula (I k: B is Η; A, C is Br; D is 011乂 is _ prime, Cte alkyl, CN, lower perfluoroalkyl, Cn alkanoyl, aralkoxy, nitro, C alkanesulfonyl, arylsulfonyl, pyridylsulfonyl, 2- N, N-dimethylamine ethylsulfonyl; E is S or O) bromophenol, which is performed using a molecular bromine of 2 mol equivalents or more in a suitable solvent such as acetic acid. Similarly, the formula (Ij: C, D is OH; X is halogen,

Ci-6烷基，CN，低全氟烷基，Cb6烷氧基，芳烷氧基，硝基，C 烷磺醯基，芳磺醯基，吡啶磺醯基，2-N ,N-二甲胺乙磺醯基；E為S或0)雙酚可犟溴化而得式 (Ik: A 為 Η; B為 Br; C，D為 0H; 1為_素，Ci-6 烷基， CN，低全氟烷基，6烷氣基，芳烷氣基，硝基，Ci-6 alkyl, CN, lower perfluoroalkyl, Cb6 alkoxy, aralkoxy, nitro, C alkanesulfonyl, arylenesulfonyl, pyridylsulfonyl, 2-N, N-di Methylamine ethanesulfonyl; E is S or 0) bisphenol can be brominated with hydrazone to give formula (Ik: A is Η; B is Br; C, D is 0H; 1 is 素 prime, Ci-6 alkyl, CN, lower perfluoroalkyl, 6-alkane, aralkyl, nitro,

Ci-6烷磺醯基，芳磺醯基，吡啶磺醯基，2-N，N-二甲胺乙磺醯基；E為S或0)及式（Ik: A為Br; B為H; C， I)為0Η;Χ為窗素，Ci-e烷基，CN，低全氟烷基，Ci-s 烷氣基，芳烷氣基，硝基，烷磺醯基，芳磺醯基，吡啶磺醯基，2-N，N-二甲胺乙磺醯基；E為S或0)溴雙酚混液，其使用1莫耳當量以上分子溴，於如乙酸之適當瀋劑下進行〇此混液可依習用方法單離為純單溴化合物。 _ 3 8 _ 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 510900 A7 B7 五、發明說明（矽）反謹流稃7Ci-6 alkylsulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; E is S or 0) and formula (Ik: A is Br; B is H C, I) is 0Η; X is window element, Ci-e alkyl group, CN, lower perfluoroalkyl group, Ci-s alkane group, aralkyl group, nitro, alkanesulfonyl, arylsulfonium Group, pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; E is S or 0) bromobisphenol mixed liquid, which uses more than 1 mole equivalent of molecular bromine under a suitable sink such as acetic acid This mixture can be isolated into pure monobromo compounds according to conventional methods. _ 3 8 _ This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) -------------------- Order ------ --- line (please read the precautions on the back before filling this page) 510900 A7 B7 V. Description of Invention (Silicon)

(請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製反應流程7中其它式（I )化合物衍生物可依下法製得。式（I1:B為H; C為Η或Br; D為OH; X為歯素，Ci-6 烷基，CN，低全氟烷基，Ci_-6烷氣基，芳烷氧基，硝基，烷磺醯基，芳磺醯基，啶磺醯基，2-N，N-二甲胺乙磺醯基；E為S或0)酚可烷化以1莫耳當量以上式（X CMOaC〇2R ，其中 X 為 ci，Br，I且 R6 為 C 卜6 烷基，RW為Η) _乙酸烷酯，且以1莫耳當量以上鹼金屬磺酸_ (如磺酸鉀），於非質子溶劑如DM F反應可得式為H;A，C為Η或Br;X為鹵素，Ci-6烷基，CN ，低全氟烷基，Ci-6烷氧基，芳烷氧基，硝基，Cn 烷磺醯基，芳磺醒基，吡啶磺醯基，2-N，N-二甲胺乙磺醯基；R6為Ci — 6烷基，R6a·!!; E為S或0)之烷化物。此外，式（II: A，B為Η或Br; C，D為0H;义為®素， Ci-6烷基，CN，低全氟烷基，C^e烷氣基，芳烷氣基 -39- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印製 510900 A7 ___B7_ 五、發明說明（^ ) ，硝基，Ci-e烷磺醒基，芳磺醯基，吡啶磺醯基，2- N ，N -二甲胺乙磺醯基；E為S或0 )雙酚可二烷化以2莫耳當量以上式（X2CHR6aC02R6，其中X2為Cl, Br，I且R6 為（^ 6烷基，R6a.H)鹵乙酸烷酯，及2莫耳當量以上鹼金屬碳酸鹽（如磺酸鉀），於非質子溶劑如DMF反應可得式（IrorA, B為Η或Br; C為OCH2C〇2li6 ; X為痛素，C i - 6烷基，C N，低全氟烷基，C i _ 6烷氯基，芳烷氣基，硝基，C ^ e烷磺醯基，芳磺醯基，毗啶磺醒基， 2-N，N-二甲胺乙磺醒基；烷基，1?63為{1; E為S或0)之二烷化酯。此外，式（II: B為11或_素；A為Η或鹵素；C為H , Br 或C!_e烷氣基；D為OH; X為鹵素，烷基，CN，低全氟烷基，Ci-6烷氣基，芳烷氣基，硝基，Ci-6烷磺醯基，芳磺醯基，毗啶磺醯基，2 - N，N -二甲胺乙磺醯基；E為 S或 0)酚可與式 CH (〇H)(R6a)C〇2R6 i R6，烷基，芳烷基，芳基）之2-羥基羧酸酯，依 Mitsunobu反應（綜述參考 Oyo Mitsunobu Synthesis, 1981， 1-2?)反應得式（Ibk B為Η或鹵素；A為Η或痛素 ;(：為Η，Br或C e烷氧基；X為鹵素，C 烷基，CN ，低全氟烷基，C ^ 6烷氧基，芳烷氧基，硝基，C - 6 烷磺醯基，芳磺醯基，毗啶磺酿基，2 - N , N -二甲胺乙磺醯基；R6，烷基，芳烷基，芳基；E為S 或〇) _。其它Mitsunobu反應所需共試劑含1奠耳當量以上纒氮二羧酸Ci-6烷基二酯，如疊氮二羧酸二乙酯 -40- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7 五、發明說明（竹）或疊氮二羧酸二丙酯，及1莫耳當量以上三芳麟（如三苯_)，於如乙THF，苯或甲苯之適當溶劑，於- 20°c 〜1 2 0 °C下反應。式（1st: A， B為Η或痛素；C為H，Br或C卜6烷氣基； X為鹵素，烷基，CN，低全氟烷基，烷氣基，芳烷氧基，硝基，C 6烷磺醯基，芳磺醯基，吡啶磺醯基，2-N，N-二甲胺乙磺醯基；R6 , 烷基，芳烷基，芳基；E為S或0)單酯及式（Im: A, B為Η或 131—，0為0(：112(：021^6 ;Χ 為鹵素，Ci-6 烷基，CN，低全氟烷基，C^e烷氧基，芳烷氧基，硝基，Ci-e烷磺醯基，芳磺醯基，吡啶磺醯基，2-N，卜二甲胺乙磺醯基；Re為^»^烷基，Rfca為Η; E為S或0)雙酯可依標準方法轉為相對羧酸物而得式（Iffl: A，B為11或_素； C為H，Br或Ci-e烷氧基；乂為_素，Cp8烷基，CN，低全氟烷基，Cb6烷氧基，芳烷氧基，硝基，C^e烷磺醯基，芳磺醯基，H啶磺醯基，2-N，卜二甲胺乙磺醯基；R6為H; ^&為^ —6烷基，芳烷基，芳基；E為S 或0)單羧酸及式（Ιιη·· A，B為Η或Br; C為0CH2C02R6 义為_素，Ci-6烷基，CN，低全氟烷基，“-6烷氧基，(Please read the notes on the back before filling out this page.) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs. Other derivative compounds of formula (I) in Reaction Scheme 7 can be prepared according to the following method. Formula (I1: B is H; C is rhenium or Br; D is OH; X is halogen, Ci-6 alkyl, CN, lower perfluoroalkyl, Ci-6 alkanoyl, aralkoxy, nitrate Group, alkylsulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; E is S or 0) Phenols can be alkylated with 1 molar equivalent of CMOaC〇2R, where X is ci, Br, I and R6 is C 6 alkyl, RW is Η) _ alkyl acetate, and at least 1 molar equivalent of alkali metal sulfonic acid (such as potassium sulfonate), in Aprotic solvents such as DM F can be obtained by the formula H; A, C is fluorene or Br; X is halogen, Ci-6 alkyl, CN, lower perfluoroalkyl, Ci-6 alkoxy, aralkoxy , Nitro, Cn alkylsulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; R6 is Ci-6 alkyl, R6a !!; E is S Or 0). In addition, the formula (II: A, B is fluorene or Br; C, D is 0H; meaning is ®, Ci-6 alkyl, CN, lower perfluoroalkyl, C ^ e alkyl group, aralkyl group -39- This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 ___B7_ 5. Description of the Invention (^), Nitro, Ci-e Sulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; E is S or 0) Bisphenol can be dialkylated to 2 mol equivalents above formula (X2CHR6aC02R6, Where X2 is Cl, Br, I and R6 is (^ 6 alkyl, R6a.H) alkyl haloacetate, and an alkali metal carbonate (e.g. potassium sulfonate) of more than 2 mole equivalents, reacted in an aprotic solvent such as DMF Available formula (IrorA, B is fluorene or Br; C is OCH2C02li6; X is analgesin, Ci-6 alkyl, CN, lower perfluoroalkyl, Ci-6 alkylchloro, aralkylamino , Nitro, C ^ e alkylsulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; alkyl, 1 to 63 for {1; E for S Or 0) of a dialkylated ester. In addition, formula (II: B is 11 or _ prime; A is fluorene or halogen; C is H, Br or C! _E alkyl group D is OH; X is halogen, alkyl, CN, lower perfluoroalkyl, Ci-6 alkylamino, aralkylamino, nitro, Ci-6 alkylsulfonyl, arylsulfonyl, pyridylsulfonyl Fluorenyl, 2-N, N-dimethylamine ethylsulfonyl; E is S or 0) Phenol can interact with the formula CH (〇H) (R6a) C02R6 i R6, alkyl, aralkyl, aryl ) Of 2-hydroxycarboxylic acid ester, according to the Mitsunobu reaction (for a review, see Oyo Mitsunobu Synthesis, 1981, 1-2?) To obtain the formula (Ibk B is fluorene or halogen; A is fluorene or painin; Or Ce alkyloxy; X is halogen, C alkyl, CN, lower perfluoroalkyl, C ^ 6 alkoxy, aralkyloxy, nitro, C-6 alkanesulfonyl, arylenesulfonyl , Pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; R6, alkyl, aralkyl, aryl; E is S or 〇). Other co-reagents required for Mitsunobu reaction contain 1 Ci-6 alkyl diesters with more than Moore equivalents, such as diethyl azide dicarboxylate-40- This paper is sized for China National Standard (CNS) A4 (210 X 297 mm)- ------------------ Order --------- line (Please read the notes on the back before filling this page) Member of the Intellectual Property Bureau of the Ministry of Economic Affairs Printed by the Industrial and Consumer Cooperatives 510900 A7 B7 V. Description of the invention (Bamboo) or dipropyl azide dicarboxylic acid, and triaryllin (such as triphenyl) above 1 mole equivalent, suitable for such as ethyl THF, benzene or toluene Solvent, react at -20 ° c ~ 120 ° C. Formula (1st: A, B is fluorene or analgesin; C is H, Br, or C 6 alkane group; X is halogen, alkyl, CN, lower perfluoroalkyl group, alkane group, aralkoxy group, Nitro, C 6 alkylsulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; R6, alkyl, aralkyl, aryl; E is S or 0) Monoester and formula (Im: A, B is Η or 131—, 0 is 0 (: 112 (: 021 ^ 6; X is halogen, Ci-6 alkyl, CN, lower perfluoroalkyl, C ^ e-alkoxy, aralkyloxy, nitro, Ci-e-alkanesulfenyl, arylsulfonyl, pyridylsulfonyl, 2-N, dimethylamine ethylsulfonyl; Re is ^ »^ alkane Rfca is Η; E is S or 0) The diester can be converted to a relative carboxylic acid by a standard method to obtain the formula (Iffl: A, B is 11 or _ prime; C is H, Br or Ci-e alkoxy乂 is _ prime, Cp8 alkyl, CN, lower perfluoroalkyl, Cb6 alkoxy, aralkoxy, nitro, C ^ e alkylsulfonyl, arylsulfonyl, H-pyridylsulfonyl , 2-N, dimethylaminoethanesulfonyl; R6 is H; ^ & is ^ -6 alkyl, aralkyl, aryl; E is S or 0) monocarboxylic acid and formula (Ιιη ··· A, B is Η or Br; C is 0CH2C02R6 meaning _ prime, Ci-6 alkyl, CN, Low perfluoroalkyl, "-6alkoxy,

芳烷氧基，硝基，C P6烷磺醯基，芳磺醯基，Ptt啶磺醯基，2-N，N -二甲胺乙磺醯基；R6，1{6&為11; E為S或〇)二羧酸酯。此轉形反應可於存在1莫耳當量以上鹸金屬氫氧化物，如N a 0 Η，之水及如T H F，二_烷及低烴醇 (如甲醇）之共溶爾，或THF及低烴醇混液，於0〜40°C -41- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁)Aralkyloxy, nitro, C P6 alkylsulfonyl, arylsulfonyl, Pttidinesulfonyl, 2-N, N -dimethylamine ethylsulfonyl; R6, 1 {6 &11; E Is S or O) dicarboxylic acid ester. This transformation reaction can be in the presence of more than 1 mole equivalent of a metal hydroxide, such as Na 0 Η, in water and co-solvents such as THF, dioxane, and a lower hydrocarbon alcohol (such as methanol), or THF and low Hydrocarbon alcohol mixture, at 0 ~ 40 ° C -41- This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) ------------------ --Order --------- line (Please read the precautions on the back before filling this page)

510900 A7 B7 五、發明說明（心）下進行510900 A7 B7 V. Description of the Invention (Heart)

反應流程8中其它式（I)化合物衍生物可依下法製得。式（In·· X為歯素，C^6烷基，CN，低全氟烷基， Ci-6烷氣基，芳烷氧基，硝基，Ci-6烷磺醯基，芳磺醒基，毗啶磺_基，2-N，N -二甲胺乙磺醯基；Y為Η; E 為S或0)乙酸鹽可與鹵化劑反應，特定為可苄型溴化或氯化者，如1莫耳當量以上N-溴丁二醯亞胺，N-氯丁二醯亞胺或硫醯氯，可得式（In: 乂為_素，C ^ 6烷基，CN，低全氟烷基，Ci-8烷氧基，芳烷氣基，硝基，Ci-e烷磺醯基，芳磺醯基，曝啶磺醯基，24，N -二甲胺乙磺_基；Y為Cl, Br; E為S或0)鹵乙酸鹽。此反應可於適當溶劑，如二氯甲烷或四氯化磺，於〇 °C〜室溫下反應。式（In:义為_素，烷基，CN，低全氟烷基，The derivatives of other compounds of formula (I) in Reaction Scheme 8 can be prepared by the following method. Formula (In ·· X is halogen, C ^ 6 alkyl, CN, lower perfluoroalkyl, Ci-6 alkanoyl, aralkoxy, nitro, Ci-6 alkanesulfonyl, arylsulfonium , Pyridylsulfonyl, 2-N, N -dimethylamine ethylsulfonyl; Y is fluorene; E is S or 0) Acetate can react with halogenating agents, specifically benzyl bromide or chlorinated For example, if N-bromobutanediimide, N-chlorobutanediimide or thionyl chloride is more than 1 mole equivalent, the formula (In: 乂 is _ prime, C ^ 6 alkyl, CN, low Perfluoroalkyl, Ci-8 alkoxy, aralkylamino, nitro, Ci-e alkanesulfonyl, arylenesulfonyl, amidinylsulfonyl, 24, N-dimethylamine ethylsulfonyl ; Y is Cl, Br; E is S or 0) haloacetate. This reaction can be performed in a suitable solvent, such as dichloromethane or sulfonic tetrachloride, at 0 ° C ~ room temperature. Formula (In: meaning _ prime, alkyl, CN, low perfluoroalkyl,

Ch 6烷氧基，芳烷氣基，硝基，Ci- 6烷磺醯基，芳磺醯基，粃啶磺醯基，2-N，二甲胺乙磺醯基；Y為C1， -42- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 Φ. (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製經濟部智慧財產局員工消費合作社印製 510900 A7 B7 五、發明說明（4l )Ch 6 alkoxy, aralkylamino, nitro, Ci-6 alkanesulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, dimethylamine ethylsulfonyl; Y is C1,- 42- This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) -------------------- Order -------- -Line Φ. (Please read the notes on the back before filling out this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs Printed by the Employee Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs Printed by 510900 A7 B7

Br ; E為S或0)鹵乙酸鹽可輿1奠耳當量以上親質子劑（親核劑），如烷氣化物（Μ 0 R 1 )，硫（M S R 1 )或胺 (NHR 1 R 2 )(式中Μ為鹼金屬，如Na，Li或K; R1， R2為H，6烷基，芳基，或芳烷基），於適當溶劑，如THF，DMF或二氯甲烷反_可得式（In:义為®素，Ci-6 烷基，CN，低過氟烷基，烷氣基，芳烷氣基，硝基，Ci-e烷磺醯基，芳磺醯基，Bft啶磺醯基，2-N，N-二甲胺乙磺醯基；Y為OR1 ，SR1 , NPR2，其中R1 ，R. 2為Η，C卜6烷基，芳基，或芳烷基；E為S或0)化合物。當式（In: 乂為_素，C^6烷基，CN，低全氟烷基，烷氣基，芳烷氧基，硝基，Ci-e烷磺醯基，芳磺醯基，％啶磺醯基，2-N，N-二甲胺乙磺基；Y為 Cl，Br; E為S或0)化合物與親質子劑反應時，可同時喪失乙醯基而得式（Ιο: B，D為Η·，Χ為鹵素，烷基，CN，低全氟烷基，Ch6烷氣基，芳烷氣基，硝基， Cb6烷磺醯基，芳磺醯基，_啶磺醯基，2-N,卜二甲胺乙磺_基；Y為OR1 ，SR1 ，NPR2，其中R1 ，R2 為H，Ci-6烷基，芳基，或芳烷基；E為S或0)化合物。式（In: B，D為Η; X為齒素，C卜6烷基，CN，低全氟焼基，Ci-6院氧基，芳院氣基，硝基，Ci-6院磺醯基，芳磺醯基，毗啶磺醯基，21，N -二甲胺乙磺醯基； Y 為 OR1 ，SR 1 ，NR 1 R 2 ,其中 R1 ，R2 為 H, Ci_-6 烷基，芳基，或芳烷基；E為S或0)化合物可去醯化而得式（Ιο: B，D為Η; X為_素，（^一6烷基，CN，低全氟 -43- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂--------- (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7_ 五、發明說明（P ) 烷基，C卜s烷氣基，芳烷氧基，硝基，C卜6烷磺醯基，芳磺醯基，毗啶磺醯基，2-N，N -二甲胺乙磺醯基； Y為 Cl，Br，OR 1 , SR 1 ，NR 1 R 2 ,其中 R1 ，R2 為 H, C i- e烷基，芳基，或芳烷基；E為S或0)化合物。去醯化反應含使用水溶液其中使用1莫耳當量以上如N a 0 Η鹼金屬氫氧化物之水，與共溶劑如THF，二鸣烷或低烴醇 (如甲醇），或THF及低烴醇之混液，於0°C〜40°C之下反應〇亦可使用酸性條件，其將化合物與1奠耳當量以上礦物酸（如HC1或硫酸）於水中，與存在或無如THF之共溶劑，於室溫〜8 0 °C下反應。式（Ιο: B，D為H; 乂為_素，Ci-6烷基，CN,低全氟院基，Ci-6綜氧基，芳院氣基，硝基，Ci-6続磺醱基，芳磺醯基，毗啶磺醯基，2 _ N，卜二甲胺乙磺醯基 ;¥為（：1，Br，OR1 ，SR1 , NR1!?2，其中 R1 ，R2 為 Η ，C ι-6烷基，芳基，或芳烷基；Ε為S或0)化合物可於 2個位置溴化而得式（Ιο: B，D為Br·，素，C&6 烷基，CN,低全氟烷基，烷氣基，芳烷氯基，硝基，C 烷磺醯基，芳磺醯基，毗啶磺醯基，2-N，N-二甲胺乙磺 _ 基；Y 為 Cl，Br，OR1，SR1，NR1!?2, 其中R1，R2為H，Ci-6烷基，芳基，或芳烷基；E為S 或0)二溴酯化合物，傺使用2莫耳當量以上分子溴，於如乙酸之適當溶劑下進行。亦可使用1〜1 5莫耳當量之乙酸鹽，如乙酸鉀或乙酸鈉，作為共試劑，但其並非必需試劑。 -44- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） ----1-----—I — I-----訂·-------- (請先閱讀背面之注意事項再填寫本頁) 510900 A7 B7 五、發明說明（G)Br; E is S or 0) The haloacetate can be more than 1 molar equivalent of a protic agent (nucleophile), such as an alkane gas (M 0 R 1), sulfur (MSR 1), or an amine (NHR 1 R 2 ) (Where M is an alkali metal, such as Na, Li or K; R1, R2 is H, 6 alkyl, aryl, or aralkyl), in a suitable solvent, such as THF, DMF or dichloromethane The formula (In: meaning 素 prime, Ci-6 alkyl, CN, perfluoroalkyl, alkane, aralkyl, nitro, Ci-e alkylsulfonyl, arylsulfonyl, Bft Pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; Y is OR1, SR1, NPR2, where R1, R. 2 are pyrene, C6 alkyl, aryl, or aralkyl; E is an S or 0) compound. When the formula (In: 乂 is _ prime, C ^ 6 alkyl, CN, lower perfluoroalkyl, alkane, aralkoxy, nitro, Ci-e alkylsulfonyl, arylsulfonyl,% Pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; Y is Cl, Br; E is S or O) When a compound reacts with a proton-producing agent, it can simultaneously lose ethenyl to obtain the formula B, D are Η ·, X is halogen, alkyl, CN, lower perfluoroalkyl, Ch6 alkylamino, aralkylamino, nitro, Cb6 alkylsulfonyl, arylsulfonyl, _pyridylsulfonium Group, 2-N, dimethylamine ethylsulfonyl group; Y is OR1, SR1, NPR2, where R1, R2 is H, Ci-6 alkyl, aryl, or aralkyl; E is S or 0) Compound. Formula (In: B, D is fluorene; X is dentin, C 6 alkyl, CN, low perfluorofluorenyl, Ci-6 oxo, aryl oxo, nitro, Ci-6 sulfonium Group, arylsulfonyl, pyridinsulfonyl, 21, N-dimethylamine ethylsulfonyl; Y is OR1, SR1, NR1R2, where R1, R2 are H, Ci-6 alkyl, Aryl, or aralkyl; E is S or O) Compounds can be dephosphorylated to give formula (Ιο: B, D is Η; X is _ prime, (^ -6 alkyl, CN, low perfluoro-43 -This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) -------------------- Order --------- (Please read the notes on the back before filling out this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7_ V. Description of the invention (P) Alkyl, Cs alkyl, aralkyloxy, nitro , C 6 alkylsulfonyl, arylsulfonyl, pyridinsulfonyl, 2-N, N -dimethylamine ethylsulfonyl; Y is Cl, Br, OR 1, SR 1, NR 1 R 2 Where R1 and R2 are H, Ci-e alkyl, aryl, or aralkyl; E is S or O) compounds. The dehydration reaction contains the use of an aqueous solution in which more than 1 mole equivalent is used, such as N a 0 Η Alkali gold The hydroxide water reacts with a co-solvent such as THF, dioxane or a lower hydrocarbon alcohol (such as methanol), or a mixture of THF and a lower hydrocarbon alcohol at 0 ° C ~ 40 ° C. Acidic conditions can also be used. It reacts a compound with a mineral acid (e.g., HC1 or sulfuric acid) in water of more than 1 mole equivalent in water, and a co-solvent with or without THF at room temperature to 80 ° C. Formula (Ιο: B, D is H; 乂 is _ prime, Ci-6 alkyl, CN, low perfluorinated radical, Ci-6 comprehensive oxygen, aromatic radical, nitro, Ci-6 fluorenylsulfonyl, arylsulfonyl, adjacent Pyridylsulfonyl, 2_N, dimethylamine ethylsulfonyl; ¥ is (: 1, Br, OR1, SR1, NR1!? 2, where R1, R2 are fluorene, C-6 alkyl, aromatic Group, or aralkyl group; E is S or 0) compounds can be brominated at two positions to obtain the formula (Ιο: B, D is Br ·, prime, C & 6 alkyl, CN, lower perfluoroalkyl, Alkyl, aralkylchloro, nitro, C alkanesulfonyl, arylenesulfonyl, pyridinsulfonyl, 2-N, N-dimethylamineethanesulfonyl; Y is Cl, Br, OR1 , SR1, NR1 !? 2, where R1, R2 are H, Ci-6 alkyl, aryl, or aralkyl; E is S or 0) Dibromoester compound, 傺 uses 2 Ear equivalent molecular bromine above, within a suitable solvent such as acetic acid at. 5 may also be used 1~1 molar equivalents of acetate, such as potassium acetate or sodium acetate, as a co-agent, but the agent is not necessarily required. -44- This paper size applies to China National Standard (CNS) A4 specification (210 X 297 mm) --------------- I — I ----- Order · ------- -(Please read the notes on the back before filling out this page) 510900 A7 B7 V. Description of the invention (G)

(請先閱讀背面之注意事項再填寫本頁) 反應流程9中其它式（I)化合物衍生物可依下法製得。式（Ip: B, D為H,鹵素，CN，Ci_e烷基，芳基，芳烷基，硝基；X為H, _素，C 烷基，CN，低全氟烷基，Ci_6烷氧基，芳烷氧基，硝基，Ci-8烷磺醯基，芳磺酸基，Bft啶磺醯基，2-N，N-二甲胺乙磺醯基；Y為 H， C1, Br, OR 1 ， SR 1 ， NR 1 R 2 ,其中 R1 , R2 為 H， Ci-6烷基，芳基，或芳烷基；E為S或0)酯可烷化以1 莫耳當量以上式（X2 CH2 C02 R6，其中X2為Cl，Br，經濟部智慧財產局員工消費合作社印製或I且R6為C^6烷基），且以1莫耳當量以上鹼金屬磺酸鹽（如磺酸鉀），於非質子瀋劑如DMF反應可得式（Iq ·· B，D為H，鹵素，CN，Ci-e烷基，芳基，芳烷基，硝基；X為H,鹵素，Ci-s烷基，CN，低全氟烷基，Cn 烷氧基，芳烷氧基，硝基，烷磺醯基，芳磺醯基，毗啶磺_基，2-N，N-二甲胺乙磺醯基；Y為H，Cl, Br ，OR 1 ，SR 1，NR 1 R 2 ,其中 R1 ，R2 為 H，Ci-s 烷基，芳基，或芳烷基；w為co2r6 ;Rs為H，R6為 -4 5 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 B7 五、發明說明（#) c 6烷基；E為S或0)之烷化化合物。 (請先閱讀背面之注意事項再填寫本頁) 式（Iq: B，D為H，鹵素，CN，C：li烷基，芳基，芳烷基，硝基；X為H,鹵素，Ci-e烷基，CN,低全氟烷基，Ci_6烷氧基，芳烷氣基，硝基，烷磺醯基，芳磺醯基，吡啶磺醒基，2-N，N-二甲胺乙磺醯基；Y為 H, Cl，Br，OR 1 , SR 1 ，NR 1 R 2 ,其中 R1 ，R2 為 H ，C^e烷基，芳基，或芳烷基；E為S或0)之酚可與式 CH ( OH) ( R 5 ) CO 2 R 6 (R5 為 H，Cil 烷基，芳烷基，芳基，C Η 2 ( 1 Η -眯唑-4 -基），C Η 2 ( 3 - 1 Η -吲 B朵），C Η 2 C Η 2 ( 1 , 3 -二氧- 1，3 -二氫-異吲哚-2 -基）， CH 2 CH 2 ( 1 -氣一1 , 3 -二氯一異 B引時一 2 -基），CH 2 ( 3- 毗啶基），CH2C02R6 (较6為〇1-8烷基））之2-羥基羧酸酯，依Mitsunobu反應（綜述參考Oyo Mitsunobu Synthesis， 1981， 1-27)反應得式（Iq: B， D為 H，痛素，CN，Cb6烷基，芳基，芳烷基，硝基；X為H,鹵素，Ci-6烷基，CN，低全氟烷基，Ci-6烷氧基，芳烷氧基，硝基，Ci-e烷磺醯基，芳磺醯基，Bft啶磺醯基， 2-N，N -二甲胺乙磺醒基；Y為 H，Cl，Br，OR1 , SR1 ，經濟部智慧財產局員工消費合作社印製 N R 1 R 2 ,其中Ri , R2為H，Ci-6烷基，芳基，或芳烷基；W為C02Re ;RS為H，Ci-e烷基，芳烷基，芳基，CH 2 ( 1 Η -眯唑-4 -基），CH 2 ( 3 - 1 Η - _ Β朵）， C Η 2 C Η 2 <1， 3 -二氧一1， 3 -二氯一異 Ρ3|Β朵一2 -基）， C Η 2 C Η 2 ( 1 -氧一1， 3 -二氯一異叫時一2 ·基），CH 2 ( 3 - 毗啶基），CH2C02Re (R6為Ci-6烷基）；£為3或0) -46- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印製 510900 A7 B7___ 五、發明說明（K ) 之酯。其它Mitsunobu反應所需共試劑含1莫耳當量以上疊氮二羧酸Ci-6烷基二酯，如疊氮二羧酸二乙酯或疊氮二羧酸二丙酯，及1莫耳當量以上三芳膦（如三苯瞵），於如***，T H F ,苯或甲苯之適當溶劑，於-2 0 °C 〜1 2 G °C下反應。式 CH(0H}(R5)C02R6 (R5 為 H， Ci-6 烷基，芳烷基，芳基，CH 2 ( 1 Η - B米唑一4 -基），CH 2 ( 3 — 1 Η - Β3Ι Β 朵） ,CH 2 CH 2 ( 1， 3 -二氣一 1， 3 -二氯一異 0弓| ί朵一2 -基）， CH 2 CH 2 (1-氣_1， 3 -二氯一異賴 Β呆一 2 -基），CH 2 ( 3 — 粃啶基），CH2C02Re，R6為Ci 6烷基）之2 -羥基羧酸酯為市售可得，或可依標準酯化反應，由市售可得羧酸前物製得。（S )-(+)- 2 -羥基-1 -氣-1 , 3 -二氫 -2 -異吲B朵啉丁酸甲酯可由（S )-(+)- 2 -羥基_ 1，3 -二氧-1，3-二氫-2-異吲昤啉丁酸甲酯，經序列處理以1) 硼氫化鈉於THF-水；2)三氟乙酸/氯仿；3)三乙矽烷/ 三氟乙酸及4)重磺酸鈉溶液製得。3- (Bft啶-3-基）苯乙酸乙酯可由 B·A· Lefker， W . A . H a d a , P.J.McGarry Tetrahedron Lett . 1 9 9 4， 35， 5 2 0 5 - 5 2 0 8之二步驟方法，由市售可得啶羧醛及氯乙酸乙瞻製得。式（Iq: B，D為H,鹵素，CN，烷基，芳基，芳烷基，硝基；X為H,痛素，烷基，CN,低全氟烷基，Ci-6院氧基，芳院氧基，硝基，Ci-6綜磺醱基，芳磺醯基，吡啶磺醯基，2-fJ, N-二甲胺乙磺醯基；Y為 H，Cl，Br，OR 1 ，SR 1 ，NR 1 R 2 ,其中 R1 ，R2 為 H, -47- 本紙張尺度適用中國國家標準（CNS)A4規格（210 x 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 510900 A7 B7 五、發明說明（4 )(Please read the notes on the back before filling this page.) Other derivatives of formula (I) in Reaction Scheme 9 can be prepared by the following method. Formula (Ip: B, D is H, halogen, CN, Ci_e alkyl, aryl, aralkyl, nitro; X is H, _ prime, C alkyl, CN, lower perfluoroalkyl, Ci_6 alkoxy Aryl, aralkyloxy, nitro, Ci-8 alkylsulfonyl, arylsulfonyl, Bft pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; Y is H, C1, Br OR1, SR1, NR1R2, where R1, R2 are H, Ci-6 alkyl, aryl, or aralkyl; E is S or 0) The ester can be alkylated with 1 mole equivalent above formula (X2 CH2 C02 R6, where X2 is Cl, Br, printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economy or I and R6 is C ^ 6 alkyl), and the alkali metal sulfonate (such as Potassium acid), which can be reacted in an aprotic sink such as DMF to obtain the formula (Iq ·· B, D is H, halogen, CN, Ci-e alkyl, aryl, aralkyl, nitro; X is H, halogen , Ci-s alkyl, CN, lower perfluoroalkyl, Cn alkoxy, aralkoxy, nitro, alkanesulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, N- Dimethylamine ethylsulfonyl; Y is H, Cl, Br, OR1, SR1, NR1R2, where R1, R2 are H, Ci-s alkyl, aryl, or aralkyl; w is co2r6; Rs H, R6 is -4 5-This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) 510900 A7 B7 V. Description of the invention (#) c 6 alkyl; E is S or 0)化 Compounds. (Please read the notes on the back before filling this page) Formula (Iq: B, D is H, halogen, CN, C: li alkyl, aryl, aralkyl, nitro; X is H, halogen, Ci -e alkyl, CN, lower perfluoroalkyl, Ci-6 alkoxy, aralkylamino, nitro, alkanesulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamine Ethylsulfonyl; Y is H, Cl, Br, OR 1, SR 1, NR 1 R 2, where R1, R2 are H, C ^ e alkyl, aryl, or aralkyl; E is S or 0 Phenol can be combined with the formula CH (OH) (R5) CO2R6 (R5 is H, Cil alkyl, aralkyl, aryl, C Η 2 (1 Η -oxazole-4 -yl), C Η 2 (3-1 Η -indB), C Η 2 C Η 2 (1, 3 -dioxo-1,3 -dihydro-isoindole-2 -yl), CH 2 CH 2 (1- Gas-1,2,3-dichloro-isoB, 2-hydroxy), CH 2 (3-pyridinyl), CH2C02R6 (more than 6 is 0-8 alkyl)), 2-hydroxycarboxylic acid ester, According to the Mitsunobu reaction (for a review, see Oyo Mitsunobu Synthesis, 1981, 1-27), the formula (Iq: B, D is H, analgesin, CN, Cb6 alkyl, aryl, aralkyl, nitro; X is H , Halogen, Ci-6 alkyl, CN, low perfluoroalkane Group, Ci-6 alkoxy, aralkyloxy, nitro, Ci-e alkanesulfonyl, arylsulfonyl, Bft pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; Y is H, Cl, Br, OR1, SR1, printed by NR 1 R 2 in the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, where Ri and R2 are H, Ci-6 alkyl, aryl, or aralkyl; W is C02Re; RS is H, Ci-e alkyl, aralkyl, aryl, CH 2 (1 Η -oxazole-4 -yl), CH 2 (3-1 Η-_ Β), C Η 2 C Η 2 < 1, 3 -dioxo-1, 3 -dichloro-iso-P3 | β-dio-2-yl), C Η 2 C Η 2 (1-oxy-1, 3 -dichloro-isochloro A 2 · group), CH 2 (3-pyridyl), CH2C02Re (R6 is Ci-6 alkyl); £ 3 or 0) -46- This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7___ V. Ester of invention description (K). Other co-reagents required for Mitsunobu reaction contain more than 1 mole equivalent of Ci-6 alkyl diester of azidodicarboxylic acid, such as diethyl azide dicarboxylate or dipropyl azide dicarboxylate, and 1 mole equivalent The above triarylphosphine (such as triphenylphosphonium) is reacted in a suitable solvent such as diethyl ether, THF, benzene or toluene at -20 ° C ~ 12 G ° C. Formula CH (0H) (R5) C02R6 (R5 is H, Ci-6 alkyl, aralkyl, aryl, CH 2 (1 Η-B mizole 4 -yl), CH 2 (3 — 1 Η- Β3Ι Β flower), CH 2 CH 2 (1, 3 -digas-1, 3 -dichloro-iso0 bow | ί 朵 -1 2 -yl), CH 2 CH 2 (1-gas_1, 3 -2 2-Hydroxycarboxylic acid esters of chloro-iso-iso-B- 2-yl), CH 2 (3-pyridinyl), CH 2 CO 2 Re, R 6 is Ci 6 alkyl) are commercially available or can be esterified according to standards The reaction is prepared from a commercially available carboxylic acid precursor. (S)-(+)-2-hydroxy-1 -gas-1, 3 -dihydro-2 -isoindoboroline butyric acid methyl ester can be obtained from ( S)-(+)-2 -Hydroxy-1,3-dioxo-1,3-dihydro-2-isoindolinoline butyrate methyl ester, processed sequentially with 1) sodium borohydride in THF-water; 2) Trifluoroacetic acid / chloroform; 3) Triethylsilane / trifluoroacetic acid and 4) Sodium disulfonate solution. 3- (Bftpyridin-3-yl) ethyl phenylacetate can be obtained by B.A. Lefker, W. A. Hada, PJ McGarry Tetrahedron Lett. 1 9 9 4, 35, 5 2 0 5-5 2 0 8 The two-step method is prepared from commercially available pyridalcarboxaldehyde and ethyl chloroacetate. Formula (Iq: B, D is H, halogen, CN, alkyl, aryl, aralkyl, nitro; X is H, painin, alkyl, CN, low perfluoroalkyl, Ci-6 oxygen Aryl, aryloxy, nitro, Ci-6 sulfofluorenyl, arylsulfonyl, pyridylsulfonyl, 2-fJ, N-dimethylamine ethylsulfonyl; Y is H, Cl, Br, OR 1, SR 1, NR 1 R 2, where R1 and R2 are H, -47- This paper size applies to China National Standard (CNS) A4 (210 x 297 mm) ---------- ---------- Order --------- line (please read the precautions on the back before filling this page) 510900 A7 B7 V. Description of the invention (4)

Ci-6烷基，芳基，或芳烷基；W為C02 tBu; R5為H; (請先閱讀背面之注意事項再填寫本頁) E為S或0)之酯可處理以1莫耳當量以上強鹸，如二異丙鋰醯胺，於如THF之適當溶劑及-78°C〜室溫下進行反應製得。此製法可於酯羰基引入1個陰離子α。將所得陰離子處理以1莫耳當量以上式X2 (其中X2為_素； R 5為烷基及芳烷基）烷鹵，並回溫至室溫可得式（I q : B，D為H，鹵素，CN，Ci-6烷基，芳基，芳烷基，硝基 ;X為H，_素，Ci-e烷基，CN，低全氟烷基，C卜6烷氧基，芳烷氧基，硝基，C^e烷磺醯基，芳磺醯基， %啶磺醯基，2-N，N-二甲胺乙磺醯基；Y為H，Cl，Br， OR1 ，SR1 ，NRiR2，其中 R1 ，R2 為 H，Ci-6 烷基，芳基，或芳烷基；W為C02 tBu; Rs為烷基及芳烷基 ;E為S或0)之烷酯。式（Iq·· B，D為H，鹵素，CN，Ci 一e烷基，芳基，芳烷基，硝基；X為H，鹵素，Ci-s烷基，CN,低全氟烷基，Ci-6烷氧基，芳烷氣基，硝基，Ci-e烷磺醯基，芳磺酸基，吡啶磺醯基，2-N，N-二甲胺乙磺醒基；Y為 H, Cl, Br，OR 1 ，SR 1 ，NR 1 R 2 ,其中 R1 ，R2 為 H， C^-6烷基，芳基，或芳烷基；W為C02Re ; R5為H，經濟部智慧財產局員工消費合作社印製 C i - 6烷基，芳烷基，芳基，C Η 2 ( 1 Η -眯Di - 4 -基）， CH 2 (3-lH-N|BS) ， Cfl 2 CH 2 (1， 3 -二氧-1， 3 -二氫 -異料| p朵一 2 -基），CH 2 CH 2 ( 1 -氧一1， 3 -二氯一異 B3I B朵一 2-基），CH2 (3-嗽啶基），CH2C02R6，较6為€1-8 烷基；E為S或0)之酯，使用標準方法轉為其羧酸物， _ 4 8 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印制衣 510900 A7 B7 五、發明說明（47 ) 而得式（Iq: B，D為H，_素，CN, Ci-6烷基，芳基，芳烷基，硝基； X為H， _素 ,C 1 —8 烷基， CN , 低全氟烷基， C 1 - 6 烷氣基，芳烷氧基，硝基 9 C 1 —6 烷磺醯基芳磺醒基， H啶磺醯基，2 Ν- 二甲胺乙磺醯基； Y為Η > C 1，B r ? 0R 1 , SR 1 ， NR 1 R 2 其中 R 1 > R 2 為 Η， C 1 - 6烷基，芳基，或芳烷基； W 為 C0 2 R 6 9 R 5 為 Η， C 1-6 院基，芳烷基，芳基 > CH 2 ( 1Η -眯唑 -4- 基 ) ， CH 2 (3 - 1 Η - S引B呆 > ， CH 2 CH 2 ( 1， 3 二氣 -1 , 3- 氫 -異吲 m - 2-基）， CH 2 :CH 2 (1 -氧- 1， 3- — 氫- 異吲 m -2-基 ) > CH 2 ( 3-吡啶基 ) ， CH 2 C0 2 Η Ε為S 或〇) 之羧酸〇此反應含使用水溶液其中使用含1 莫耳當量以上如NaOH之鹼金屬氫氧化物之水，與共溶劑如THF ，二鸣烷或低烴醇（如甲醇），或THF及低烴醇之混液，於0 °C〜4 G °C之下反應。亦可使用酸性條件，其將上述式（Iq)羧醇酯與1莫耳當量以上礦物酸（如HC1或硫酸）於水中與存在或無如T H F之共溶劑，於室溫〜8 0 °C 下反應。此外，亦可使用其它方法使上述（I q)酯進形酸轉化。含將式（1<1)羧醇酯與1莫耳當量以上三溴化硼或三氯化硼於二氯甲烷，於-78°C〜室溫之下反應；將1莫耳當量以上氫溴酸之乙酸於0〜5 G °C下反應；將1 莫耳當量以上含三甲矽烷溴或三甲矽烷碘之二氯甲烷，四氯化磺或乙腈，於_ 7 8〜5 0 °C下反應；與1莫耳當量以上於吡啶或蝰啉之碘化鋰，於1 〇〇 °C〜2 5 0 °C下進行反應。式（Ip: B，D為H,齒素，CN，烷基，芳基，芳 -49- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 ^一^ (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7_ 五、發明說明（W ) 烷基，硝基；X為H，_素，Ci-6烷基，CN，低全氟烷基，Ci-6焼氣基，芳院氧基，硝基，焼礎酸基，芳磺醯基，吡啶磺醒基，2-N，卜二甲胺乙磺醯基；Y為 H , Cl，Br , OR 1 ， SR 1 , NR 1 R 2 ,其中 R1 ，R2 為 H， C卜6烷基，芳基，或芳烷基；E為S或0)酚可烷化以1 莫耳當量以上三氟甲磺醯氧甲膦酸二乙酯（D.P· Phillion 及 S丄 Andrew T et. Lett. 1 9 8 6, 1 4 7 7 - 1 4 8 0 )，及 1 莫耳當量以上鹼金屬氫化物（如N a Η ),與如T H F或D M F 適當溶劑下反應得式（Iq: Β，D為Η，鹵素，CN，Cn 烷基，芳基，芳烷基，硝基；X為Η，鹵素，Ci-6烷基， CN，低全氟烷基，Ci-e烷氧基，芳烷氣基，硝基，Ci-e 烷磺醯基，芳磺醯基，吡啶磺醯基，2 - N，N -二甲胺乙磺醯基；Y為 H，Cl，Br，OR1 ，SR1 ，NR1!?2，其中 R1 ，R 2為Η，C卜6烷基，芳基，或芳烷基；W為Ρ0 3 Ε t 2 ;R5為Η; R6為Ci-e烷基；Ε為S或0)膦酸二乙酯。式（I P : B，I)為Η，痛素，C N，C i - 6烷基，芳基，芳烷基，硝基；X為H，痛素，C 烷基，CN，低全氟烷基，Ci-6烷氯基，芳烷氧基，硝基，Ci -6烷磺醯基，芳磺醯基，毗啶磺_基，2-N，N -二甲胺乙磺醯基；Y為 H , Cl , Br , OR 1 ， SR 1 ， NR 1 R 2 ,其中 R1 ， R2 為 j}， Ci_6烷基，芳基，或芳烷基；E為S或0)酚可與式 CH(0H)(R、S)P03(R6)2 (R5 為 H, Ci-6 烷基，芳烷基，芳基，R6為Ci-6烷基）之2-羥基瞵酸二酯，依 Mitsunobu反應（綜述參考 0y〇 Mitsunobu Synthesis, -50- 本紙張尺度適用中國國家標準（CNS)A4規格（210 χ 297公釐） ---------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7_ 五、發明說明（巧） 19 8 1, 1 - 2 7 )反應得式（I p : B，D 為 Η，_ 素，C N ,Ci-6 alkyl, aryl, or aralkyl; W is C02 tBu; R5 is H; (Please read the notes on the back before filling this page) E is S or 0) The ester can be treated with 1 mole Strong fluorene above equivalent weight, such as diisopropyl lithium ammonium amine, prepared in a suitable solvent such as THF and -78 ° C ~ room temperature. This method can introduce one anion α into the ester carbonyl group. The obtained anion is treated with 1 mol equivalent of the above formula X2 (where X2 is a prime element; R 5 is an alkyl group and an aralkyl group), and the temperature is returned to room temperature to obtain the formula (I q: B, D is H , Halogen, CN, Ci-6 alkyl, aryl, aralkyl, nitro; X is H, _ prime, Ci-e alkyl, CN, lower perfluoroalkyl, C 6 alkoxy, aromatic Alkoxy, nitro, C ^ e alkylsulfonyl, arylsulfonyl,% pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; Y is H, Cl, Br, OR1, SR1, NRIR2, where R1, R2 are H, Ci-6 alkyl, aryl, or aralkyl; W is CO2 tBu; Rs is alkyl and aralkyl; E is S or 0) alkyl ester. Formula (Iq ·· B, D is H, halogen, CN, Ci-e alkyl, aryl, aralkyl, nitro; X is H, halogen, Ci-s alkyl, CN, low perfluoroalkyl , Ci-6 alkoxy, aralkylamino, nitro, Ci-e alkanesulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; Y is H, Cl, Br, OR 1, SR 1, NR 1 R 2, where R1, R2 are H, C ^ -6 alkyl, aryl, or aralkyl; W is C02Re; R5 is H, Ministry of Economic Affairs wisdom Printing of Ci-6 alkyl, aralkyl, aryl, C Η 2 (1 Η-眯 Di-4 -yl), CH 2 (3-lH-N | BS), Cfl 2 CH 2 (1, 3 -dioxo-1, 3 -dihydro-isomaterial | p-dio-2yl), CH 2 CH 2 (1 -oxo-1, 3 -dichloro-iso-B3I B-duo-2 -Yl), CH2 (3-pyridinyl), CH2C02R6, which is a € 1-8 alkyl group compared to 6; E is S or 0) esters, converted to their carboxylic acids using standard methods, _ 4 8-This paper The scale is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 mm). The printed clothing of the employee consumer cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7 5. The invention description (47) and the formula (Iq: B, D is H, _ Prime, CN, Ci-6 alkyl, aryl, aralkyl, nitro; X is H, _ prime, C 1-8 alkyl, CN, lower perfluoroalkyl, C 1-6 alkane, arane Oxygen, nitro 9 C 1-6 alkylsulfonylarylsulfonyl, H-pyridylsulfonyl, 2 Ν-dimethylamine ethylsulfonyl; Y is Η > C 1, B r? 0R 1, SR 1, NR 1 R 2 where R 1 > R 2 is fluorene, C 1-6 alkyl, aryl, or aralkyl; W is C0 2 R 6 9 R 5 is fluorene, C 1-6 is radical , Aralkyl, aryl > CH 2 (1Η-oxazol-4-yl), CH 2 (3-1 Η-Sindolase), CH 2 CH 2 (1, 3 digas-1, 3-hydro-isoinm-2-yl), CH 2: CH 2 (1-oxo-1, 3- —hydro-isoinm-2-yl) > CH 2 (3-pyridyl), CH 2 C0 2 Η Ε is S or 0) carboxylic acid. This reaction contains the use of an aqueous solution in which water containing more than 1 mole equivalent of an alkali metal hydroxide such as NaOH is used with a co-solvent such as THF, dioxane or a low hydrocarbon. Alcohol (such as methanol), or a mixture of THF and a lower hydrocarbon alcohol, is reacted at 0 ° C ~ 4 G ° C. It is also possible to use acidic conditions. The carboxylic alcohol ester of the above formula (Iq) and a mineral acid (e.g. HC1 or sulfuric acid) above 1 mol equivalent in water and a co-solvent with or without THF at room temperature ~ 80 ° C Down reaction. Alternatively, other methods may be used to convert the (Iq) ester into a meta-acid. Contains the reaction of formula (1 < 1) carboxyl alcohol ester with more than 1 mole equivalent of boron tribromide or boron trichloride in dichloromethane at -78 ° C ~ room temperature; reacting more than 1 mole equivalent of hydrogen Acetic acid of bromoic acid is reacted at 0 ~ 5 G ° C; 1 mol equivalent or more of dichloromethane containing trimethylsilyl bromide or trimethylsilyl iodide, sulfonic tetrachloride or acetonitrile at _ 7 8 ~ 5 0 ° C Reaction; reacting with lithium iodide having a molar equivalent or more of pyridine or peroxoline at 100 ° C. to 250 ° C. Formula (Ip: B, D is H, dentin, CN, alkyl, aryl, aryl-49-) This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) ------ -------------- Order --------- line ^ 一 ^ (Please read the precautions on the back before filling out this page) 510900 A7 B7_ V. Description of the invention (W) alkyl, nitro; X is H, _ prime, Ci-6 alkyl, CN, lower perfluoroalkyl, Ci-6 fluorenyl, aromatic oxygen, Nitro, fluorenyl acid, arylsulfonyl, pyridylsulfonyl, 2-N, dimethylamine ethylsulfonyl; Y is H, Cl, Br, OR1, SR1, NR1R2, Where R1 and R2 are H, C6 alkyl, aryl, or aralkyl; E is S or 0) Phenol can be alkylated with 1 mol equivalent or more of difluoromethanesulfonyloxymethanephosphonic acid diethyl ester ( DP · Phillion and S 丄 Andrew T et. Lett. 1 9 8 6, 1 4 7 7-1 4 8 0), and alkali metal hydrides (such as Na a) of more than 1 mole equivalent, and such as THF or DMF Reaction in a suitable solvent gives formula (Iq: B, D is fluorene, halogen, CN, Cn alkyl, aryl, aralkyl, nitro; X is fluorene, halogen, Ci-6 alkyl, CN, low Perfluoroalkyl, Ci-e alkoxy, aralkylamino, nitro, Ci-e alkanesulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamineethanesulfonyl Y is H, Cl, Br, OR1, SR1, NR1!? 2, where R1, R2 is fluorene, C6 alkyl, aryl, or aralkyl; W is P0 3 E t 2; R5 Is Η; R6 is Ci-e alkyl; E is S or 0) diethyl phosphonic acid. Formula (IP: B, I) is fluorene, analgesic, CN, Ci-6 alkyl, aryl, aralkyl, nitro; X is H, analgesic, C alkyl, CN, low perfluoroalkane Group, Ci-6 alkylchloro, aralkyloxy, nitro, Ci-6 alkylsulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; Y is H, Cl, Br, OR1, SR1, NR1R2, where R1, R2 is j}, Ci-6 alkyl, aryl, or aralkyl; E is S or 0) Phenol can be combined with the formula CH (OH, (R, S) P03 (R6) 2 (R5 is H, Ci-6 alkyl, aralkyl, aryl, R6 is Ci-6 alkyl) 2-hydroxyphosphonic acid diester, according to Mitsunobu Reaction (for review, please refer to 0y〇 Mitsunobu Synthesis, -50- This paper size is applicable to China National Standard (CNS) A4 specification (210 x 297 mm) ------------------- --Order --------- line (Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7_ V. Description of Invention (Clever) 19 8 1, 1-2 7) to obtain the formula (I p: B, D is Η, _ prime, CN,

Ci-6烷基，芳基，芳烷基，硝基；X為Η，鹵素，Cn 烷基，CN，低全氟烷基，C：l-6烷氣基，芳烷氣基，硝基，Ci-e烷磺薩基，芳磺醯基，Bft啶磺_基，2-N，N-二甲胺乙磺醯基；Y為 Η，C 1，B r，0 R 1 ，S R 1 ，N R 1 E 2 ，其中ft1 ，R2為H，Ci-e烷基，芳基，或芳烷基；W為 P 〇 3 ( R 6 ) 2 為H，Ci-6院基，芳院基，芳基， R6為Ci-e烷基；E為S或0)磷酸二酯。其它Mitsunobu 反應所霈共試劑含1莫耳當量以上疊氮二羧酸烷基二酯，如疊氮二羧酸二乙酯或疊氮二羧酸二丙酯，及 1莫耳當量以上三芳_ (如三苯麟），於如***，T H F , 苯或甲苯之適當溶劑，於-2 0 °C〜1 2 0 °C下反應。式 C Η ( 0 H ) U 5 ) P 0 3 (R 6 ) ( R s 為 Η，C i - 6 烷基，芳烷基，芳基，R 6為C i - 6烷基）之2 -羥基鱗酸二酯可使用標準方法，由式HP (0) (R 6 ) 2 (R 6為C i - s烷基）之二烷瞵酸與式R 5 CHO ( R 5為C卜6烷基，芳烷基，芳基）之醛反應而製得。式（Iq: B，D為H，鹵素，CN，Ci-e烷基，芳基，芳烷基，硝基；X為 H，鹵素，Ci-6烷基，CN，低全氟烷基，C ^ 6烷氧基，芳烷氧基，硝基，C i - 6烷磺醯基，芳磺醯基，粃啶磺醯基，2 - N，N -二甲胺乙磺醯基；Y為 H, C 1 , Br , 0R 1 , SR 1 ，SR 1 R 2 ,其中 β1 , R2 為 Η ，C卜6烷基，芳基，或芳烷基；W為Ρ0 3 U 6 ) 2 ; R 5 為Η，C 1 - 6烷基，芳烷基，芳基，R 6為C i - e烷基；Ε -51- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線# (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7_ 五、發明說明（θ ) 為S或0) _酸二酯，可使用標準方法，轉為其麟酸，而得式（I q : B，D為Η，鹵素，C N，C i - 6烷基，芳基，芳烷基，硝基；X為H，鹵素，烷基，CN，低全氟烷基，C ^ 6烷氣基，芳烷氧基，硝基，C i，6烷磺醯基，芳磺醯基，吡啶磺醯基，2 1，N -二甲胺乙磺醯基；Y為Η ，C 1 , Br, OR 1 ，SR 1 , NR1 R 2 ,其中 R1，R2 為 h， Cl6烷基，芳基，或芳烷基；W為P02H2 ;Rs為H， Ci-e烷基，芳烷基，芳基，Re為Ci-6烷基；E為S或0) _酸。可將上逑式（Iq)膦酸二酯與2莫耳當量以上礦物酸（如HC1或硫酸）於水中，於存在或無如THF之共溶劑，於4 G〜1 G 0 °C下反應。此外，亦可使用其它方法使上逑式（Iq)二酯轉為酸。含將式（Iq)膦酸二酯與含 2莫耳當量以上三溴化硼或三氯化硼之二氯甲烷，於-78°C 〜室溫之下反應；與含2莫耳當量以上氫溴酸之乙酸，於 0〜50 °C下反應；與2莫耳當量以上三甲矽烷溴或三甲矽烷碘之二氯甲烷，四氯化磺或乙腈，於-7 8〜5 0 °C下反應；與含2莫耳當量以上碘化鋰之毗啶或Bf啉，於60〜 2 5 0 °C下反應。式（Iq: B，D為H，_素，CN，Ci-e烷基，芳基，芳烷基，硝基；X為Η，鹵素，6烷基，CN，低全氟烷基，C 6烷氧基，芳烷氧基，硝基，C b 6烷磺醱基，芳磺醯基，吡啶磺醯基，2-N, N-二甲胺乙磺醯基；Y為 H, C1, Br ? OR 1 ， SR 1 ， NR 1 R 2 ,其中 R1 ， R2 為 H ，C卜6烷基，芳基，或芳烷基；W為CO 2 R 6 ; R 5為Η， _52- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線· (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7 發明說明（π ) c i - S烷基，芳烷基，芳基，c Η 2 ( 1 Η -眯唑-4 -基）， CH 2 (3-lH-B?|B 朵）,CH 2 CH 2 (1一氣一1， 3 -二氫一異 #引 P朵-2 -基），C H 2 ( 3 - Pit 啶基），R 6 為 C 土 - 6 烷基；E 為Ci-6 alkyl, aryl, aralkyl, nitro; X is fluorene, halogen, Cn alkyl, CN, lower perfluoroalkyl, C: 1-6 alkane, aralkyl, nitro , Ci-e alkanesulfazyl, arylsulfonyl, Bft pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; Y is fluorene, C 1, B r, 0 R 1, SR 1 , NR 1 E 2, where ft1, R2 is H, Ci-e alkyl, aryl, or aralkyl; W is P 03 (R 6) 2 is H, Ci-6 is based, Fang is based, Aryl, R6 is Ci-e alkyl; E is S or 0) phosphodiester. Other co-reagents in Mitsunobu reactions contain more than 1 mole equivalent of alkyl azide dicarboxylic acid diesters, such as diethyl azide dicarboxylate or dipropyl azide dicarboxylic acid, and triaryl compounds above 1 mole equivalent. (Such as triphenyllin), in a suitable solvent such as diethyl ether, THF, benzene or toluene, and react at -20 ° C ~ 120 ° C. Formula C Η (0 H) U 5) P 0 3 (R 6) (R s is Η, Ci-6 alkyl, aralkyl, aryl, R6 is Ci-6 alkyl) 2- Hydroxyphosphonic acid diesters can be prepared using standard methods from the dioxanoic acid of formula HP (0) (R 6) 2 (R 6 is C i-s alkyl) and the formula R 5 CHO (R 5 is C 6 alkyl Aryl, aralkyl, aryl) by aldehyde reaction. Formula (Iq: B, D is H, halogen, CN, Ci-e alkyl, aryl, aralkyl, nitro; X is H, halogen, Ci-6 alkyl, CN, lower perfluoroalkyl, C ^ 6alkoxy, aralkyloxy, nitro, Ci-6 alkylsulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; Y Is H, C 1, Br, 0R 1, SR 1, SR 1 R 2, where β1, R2 are Η, C 6 alkyl, aryl, or aralkyl; W is P0 3 U 6) 2; R 5 is fluorene, C 1-6 alkyl, aralkyl, aryl, and R 6 is C i-e alkyl; E-51- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ) -------------------- Order --------- line # (Please read the notes on the back before filling this page) Intellectual Property of the Ministry of Economic Affairs Printed by the Bureau ’s Consumer Cooperatives 510900 A7 B7_ 5. Description of the Invention (θ) is S or 0) _ acid diester, which can be converted to its linoleic acid using standard methods, and the formula (I q: B, D is Η, Halogen, CN, Ci-6 alkyl, aryl, aralkyl, nitro; X is H, halogen, alkyl, CN, lower perfluoroalkyl, C ^ 6alkane, aralkoxy, Nitro, C i, 6 alkanesulfonyl Arylsulfonyl, pyridylsulfonyl, 2 1, N-dimethylamine ethylsulfonyl; Y is fluorene, C 1, Br, OR 1, SR 1, NR1 R 2, where R1, R2 are h, Cl6 Alkyl, aryl, or aralkyl; W is P02H2; Rs is H, Ci-e alkyl, aralkyl, aryl, Re is Ci-6 alkyl; E is S or O) acid. The phosphonic acid diester of the above formula (Iq) can be reacted with 2 mol equivalent or more of mineral acid (such as HC1 or sulfuric acid) in water, in the presence or absence of a co-solvent such as THF, at 4 G ~ 1 G 0 ° C . Alternatively, other methods can be used to convert the diester of formula (Iq) to an acid. Contains a reaction of a phosphonic acid diester of formula (Iq) with dichloromethane containing boron tribromide or boron trichloride containing more than 2 mole equivalents at -78 ° C ~ room temperature; and containing more than 2 mole equivalents Acetic acid hydrobromide, react at 0 ~ 50 ° C; with 2 molar equivalents of trimethylsilyl bromide or trimethylsilyl iodide in dichloromethane, sulphur tetrachloride or acetonitrile, at -78 ~ 50 ° C React; react with pyrimidine or Bf morpholine containing lithium iodide of more than 2 mole equivalents at 60 ~ 250 ° C. Formula (Iq: B, D is H, _ prime, CN, Ci-e alkyl, aryl, aralkyl, nitro; X is fluorene, halogen, 6 alkyl, CN, lower perfluoroalkyl, C 6 alkoxy, aralkoxy, nitro, C b 6 alkylsulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; Y is H, C1 , Br? OR 1, SR 1, NR 1 R 2, where R 1, R 2 is H, C 6 alkyl, aryl, or aralkyl; W is CO 2 R 6; R 5 is fluorene, _52- Paper size applies to China National Standard (CNS) A4 specification (210 X 297 mm) -------------------- Order --------- Line · (Please read the notes on the back before filling out this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7 Invention Description (π) ci-S alkyl, aralkyl, aryl, c Η 2 (1 Η -Oxazole-4 -yl), CH 2 (3-lH-B? | B flower), CH 2 CH 2 (1 gas-1, 3 -dihydro-iso #Induction of P 2 -yl), CH 2 (3-Pit pyridyl), R 6 is C -6 alkyl; E is

S或0)之酯可轉為其相對式（Iq: B, D為H,鹵素，CN, Ci-6烷基，芳基，芳烷基，硝基；X為H，鹵素，Cn 烷基，CN，低全氟烷基，Ci-6烷氣基，芳烷氣基，硝基，Ci_6烷磺醯基，芳磺醯基，毗啶磺醯基，24, N-二甲胺乙磺醯基；Y為 H, Cl， Br， 0R 1 ， SR 1 ， NR 1 R2 ，其中R1 ，R2為H，Ci-6烷基，芳基，或芳烷基；W為 C0NH 2 ;R5為H，Ci-6烷基，芳烷基，芳基，CH2 (1H -眯 _ 一 4 -基），CH 2 ( 3 - 1 Η - »弓| P朵），CH 2 CH 2 ( 1 -氣-1 ，3 -二氫-異吲呤-2 -基），C Η 2 ( 3 -吡啶基）；Ε為S或0 ) 之一級羧酸醱胺，其偽由酯與溶於低醇溶劑（如甲醇或乙醇）之胺氣，於0〜1 0 0 °C下反應。此外，式 (I q ： B , D為Η 鹵素 > CN ， C 1 -6 烷基，芳基芳烷基，硝基；X為H，齒素， C 1 - 6 烷基， C Ν , 低全氟院基 > C 1- 6 烷氧基，芳院氣基 9 硝基，C 1- 6 烷磺醯基芳磺醯基，吡啶磺醯基， 2 -Ν > Ν - 二甲胺乙磺醯基； Υ 為 Η, C1 , Br , 0R 1 ， SR 1 9 NR 1 R 2 ，其中 R 1 9 R 2為Η ， C 1 - 6 烷基，芳基或芳烷基； W為 C0 2 Η ； R - '為Η 9 C 1 6院基，芳烷基，芳基， CH 2 (1 Η- 眯 m -4- 基 ) 9 CH 2 (3-1 Η-吲 η ) 9 CH 2 CH 2 ( 1 , 3~ 二氣 -1， 3 -二氯一異 B弓| P朵一2 — 基），CH 2 CH 2 ( 1 一氣一 1， 3 -二氯一異吲哚-2 -基），C Η 2 ( 3 - Bft啶基）；E為S或0 )之羧酸 -53- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7_ 五、發明說明（P) 可轉為相對如式（Iq: B，D為H，痛素，CN，Ci-6烷基，芳基，芳烷基，硝基；X為Η，鹵素，C卜e烷基，CN，低全氟烷基，Ci-8烷氧基，芳烷氣基，硝基，Ci-e烷磺醯基，芳磺醯基，吡啶磺醯基，2 - N，N -二甲胺乙磺醯基；Y為 H，Cl, Br，OR1 ，SR1，NPR2，其中 R1 ，R2為H, Cb6烷基，芳基，或芳烷基；W為C02NH2 ，C0NH0H , C0NH(CH2)2CN;Rs 為 H, C：L-e 烷基，芳烷基，芳基，C Η 2 ( 1 Η -眯唑-4 -基），C Η 2 ( 3 - 1 Η - B引 ^ ) ， CH 2 CH 2 (1， 3婦二氣一1， 3-二氯一異 D 引時一2 醒基），CH 2 CH 2 (1-氧一1， 3 -二氯一異 ϋ 引 P 朵一2 -基），CH 2 ( 3- 吡啶基）；^為S或0)之羧酸醯胺。其可使用標準方法將羧酸轉為羧酸醒胺。此方法含將酸轉為活化酸，再與 1莫耳當量以上胺反應。此處胺可為氫氣化銨，羥胺及2 -胺丙腈之銨。活化羧酸之方法含將該酸與1莫耳當量以上草酸氯或磺醯氣反應，可得羧醯氯於如二氯甲烷，氯仿或***之適當溶劑。此反應常由少量（0.01〜0.1莫耳當量）之二甲基甲醯胺催化。其它活化羧酸之方法含將該酸與1莫耳當量以上二璟己基磺化二亞胺，於存在或無1莫耳當量以上羥苯駢***，於如二氯甲烷或二甲基甲醯胺之適當溶劑，於〇〜6 0 °C下反應^ 式（Ip: B，D為H,鹵素，CN，C1〜6烷基，芳基，芳烷基，硝基；X為H，鹵素，Ci_-6烷基，CN，低全氟烷基，烷氧基，芳烷氧基，硝基，烷磺薩基，芳磺醯基，毗啶磺醯基，2 - N，I二甲胺乙磺醯基；Y為 -54- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） ------------mw------- -訂--------—線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7_ 五、發明說明（〇) H, Br，OR 1 ，SR 1 ，NR 1 R 2 ,其中 R1 ，R2 為 H, C 烷基，芳基，或芳烷基；E為S或0)酚可烷化以1 莫耳當量以上式（X 2 C Η 2 C N其中X 2為C 1，B r或I) 腐乙腈，及1莫耳當量以上鹼金屬磺酸鹽（如磺酸鉀） ,於極性非質子溶劑如DMF反喔可得式（Iq: B，D為H, 鹵素，CN，C卜6烷基，芳基，芳烷基，硝基；X為H, i菌素，C卜6烷基，CN，低全氟烷基，C 烷氣基，芳烷氧基，硝基，烷磺醯基，芳磺醯基，lift啶磺醯基，2-N，N-二甲胺乙磺醒基；Y為H，Cl，Br, 0R1 , SR1 ，NPR2,其中R1，R2為H, C卜e烷基，芳基，或芳烷基；W為CM; R5為Η; E為S或0)之腈。此外，式（Iq: B，D為H，_素，CN, Ci-e烷基，芳基，芳烷基，硝基；X為H，_素，Ci-6烷基，CN,低全氟烷基，Ci 6烷氧基，芳烷氧基，硝基，Ci-6烷磺醯基，芳磺醯基，吡啶磺醯基，2-N，N -二甲胺乙磺醯基；Y 為 H，Cl，Br，OR1 ，SR1 , NPR2，其中 R1, R. 2為H，Ci-6烷基，芳基，或芳烷基；W為CONH2 ;S or 0) can be converted to its relative formula (Iq: B, D is H, halogen, CN, Ci-6 alkyl, aryl, aralkyl, nitro; X is H, halogen, Cn alkyl , CN, lower perfluoroalkyl, Ci-6 alkylamino, aralkylamino, nitro, Ci-6 alkylsulfonyl, arylenesulfonyl, pyridinsulfonyl, 24, N-dimethylamineethanesulfonyl Fluorenyl; Y is H, Cl, Br, 0R1, SR1, NR1R2, where R1, R2 are H, Ci-6 alkyl, aryl, or aralkyl; W is CONH2; R5 is H , Ci-6 alkyl, aralkyl, aryl, CH2 (1H -fluorenyl-4 -yl), CH 2 (3-1 pyrene-»bow | P flower), CH 2 CH 2 (1 -gas- 1,3-dihydro-isoindin-2-yl), C Η 2 (3-pyridyl); E is S or 0) a carboxylic acid amine of the first grade, which is pseudo-ester made by dissolving in a low alcohol solvent ( (Such as methanol or ethanol) amine gas at 0 ~ 100 ° C reaction. In addition, the formula (I q: B, D is Η halogen> CN, C 1-6 alkyl, aryl aralkyl, nitro; X is H, dentin, C 1-6 alkyl, C Ν, Low perfluorinated alkyl group> C 1-6 alkoxy group, aromatic alkyl 9 nitro group, C 1-6 alkylsulfonyl arylsulfonyl group, pyridylsulfonyl group, 2 -N > Ν -dimethyl Amine ethylsulfonyl; Υ is Η, C1, Br, 0R 1, SR 1 9 NR 1 R 2, where R 1 9 R 2 is Η, C 1-6 alkyl, aryl or aralkyl; W is C0 2 Η; R-'is Η 9 C 1 6 alkyl, aralkyl, aryl, CH 2 (1 Η- 眯 m -4-yl) 9 CH 2 (3-1 Η-indη) 9 CH 2 CH 2 (1, 3 ~ Digas-1, 3 -dichloro-iso-B-bow | P-Duo-2 —yl), CH 2 CH 2 (1 mono-gas- 1, 3 -dichloro-isoindole-2 -Based), C Η 2 (3-Bft pyridyl); E is S or 0) carboxylic acid-53- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ---- ---------------- Order --------- line (Please read the notes on the back before filling out this page) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs510900 A7 B7_ 5. Description of the invention (P) can be converted to a relative formula (Iq: B, D is H, analgesin, CN, Ci-6 alkyl, aryl, aralkyl, nitro; X is Η, Halogen, C alkyl, CN, lower perfluoroalkyl, Ci-8 alkoxy, aralkylamino, nitro, Ci-e alkylsulfonyl, arylsulfonyl, pyridylsulfonyl, 2 -N, N -dimethylamine ethylsulfonyl; Y is H, Cl, Br, OR1, SR1, NPR2, where R1, R2 are H, Cb6 alkyl, aryl, or aralkyl; W is CO2NH2, C0NH0H, C0NH (CH2) 2CN; Rs is H, C: Le alkyl, aralkyl, aryl, C Η 2 (1 Η -oxazole-4 -yl), C Η 2 (3-1 Η-B ^), CH 2 CH 2 (1, 3 dioxan-1, 3-dichloro-iso-D, epoch-2), CH 2 CH 2 (1-oxy-1, 3-dichloro-iso ϋ Introduce P 2 -yl), CH 2 (3-pyridyl); ^ amine carboxylic acid amine. It can be converted to carboxylic acid amine using standard methods. This method involves converting the acid to an activated acid and reacting with more than 1 mole equivalent of amine. Here the amine may be ammonium hydride, hydroxylamine and ammonium of 2-amine propionitrile. The method for activating the carboxylic acid comprises reacting the acid with more than 1 mole equivalent of chlorine oxalate or sulfonium gas to obtain carboxylic acid chloride in a suitable solvent such as dichloromethane, chloroform or ether. This reaction is often catalyzed by a small amount (0.01 to 0.1 mole equivalent) of dimethylformamide. Other methods of activating carboxylic acids include the acid with 1 mole equivalent of dioxanyl sulfonimide in the presence or absence of 1 mole equivalent of hydroxybenzotriazole, such as dichloromethane or dimethylformamide. A suitable solvent for amidine is reacted at 0 ~ 60 ° C ^ Formula (Ip: B, D is H, halogen, CN, C1 ~ 6 alkyl, aryl, aralkyl, nitro; X is H, Halogen, Ci_-6 alkyl, CN, lower perfluoroalkyl, alkoxy, aralkyloxy, nitro, alkanesulfenyl, arylsulfonyl, pyridinsulfonyl, 2-N, I di Methylamine ethylsulfonyl group; Y is -54- This paper size applies to China National Standard (CNS) A4 specification (210 X 297 mm) ------------ mw ------ --Order --------- Line (Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7_ V. Description of the invention (〇) H, Br, OR 1, SR 1, NR 1 R 2, where R1 and R2 are H, C alkyl, aryl, or aralkyl; E is S or 0) Phenol can be alkylated with 1 mole equivalent above formula (X 2 C Η 2 CN, where X 2 is C 1, B r or I) acetonitrile, and alkali metal sulfonate (such as sulfonic acid) Potassium), can be obtained in polar aprotic solvents such as DMF (Iq: B, D is H, halogen, CN, C6 alkyl, aryl, aralkyl, nitro; X is H, i bacteria Element, C 6 alkyl, CN, lower perfluoroalkyl, C alkane, aralkyloxy, nitro, alkanesulfonyl, arylenesulfonyl, lift pyridylsulfonyl, 2-N, N -Dimethylamine ethylsulfonyl; Y is H, Cl, Br, 0R1, SR1, NPR2, where R1, R2 are H, C alkyl, aryl, or aralkyl; W is CM; R5 is Η; E is S or 0) nitrile. In addition, the formula (Iq: B, D is H, _ prime, CN, Ci-e alkyl, aryl, aralkyl, nitro; X is H, _ prime, Ci-6 alkyl, CN, low total Fluoroalkyl, Ci 6 alkoxy, aralkyloxy, nitro, Ci-6 alkanesulfonyl, arylenesulfonyl, pyridylsulfonyl, 2-N, N -dimethylamine ethylsulfonyl; Y is H, Cl, Br, OR1, SR1, NPR2, where R1, R. 2 is H, Ci-6 alkyl, aryl, or aralkyl; W is CONH2;

Rs為H，Ci-6烷基，芳烷基，芳基，CH2 (1H-眯 4 -基），CH 2 (3-1H-H5I 時），CH 2 CH 2 (1， 3 -二氣一 1 ，3 — 二氯一異柯| B朵一 2 -基），CH 2 CH 2 ( 1 -氣埋 1， 3 — 二氯 -異吲時-2 -基），C Η 2 ( 3 -毗啶基）；E為S或0 )之羧酸醯胺可轉為其如式（Iq: B，D為Η，鹵素，CN，Ci-e 烷基，芳基，芳烷基，硝基·，Χ牛為H，鹵素，Ci-6烷基，CN，低全氟烷基，Ci-e烷氣基，芳烷氣基，硝基， -55- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) '^w____ 訂---------線-一經濟部智慧財產局員工消費合作社印製 510900 A7 _B7_ 五、發明說明（Μ) 烷磺醯基，芳磺醯基，吡啶磺醯基，2-Ν，Ν-二甲胺乙磺醯基；Y為 Η， C1, Br, 0R 1 ， SR 1 , NR 1 R2，其中R1 ，R2為H，Ch 6烷基，芳基，或芳烷基；W為 CN;RS為H，（U-6烷基，芳烷基，芳基，CH2 (1H-眯睡一4 -基），CH 2 ( 3 —1 Η - B 引》朵），C H 2 C Η 2 ( 1， 3 -二氧一1， 3-二氯一異 Β引 β 朵一2 -基），CH 2 CH 2 (1-氧一1， 3-二氫-異吲8朵-2 -基），C Η 2 ( 3 -曝啶基）；Ε為S或0 ) 之腈，其傺使用試劑將一級羧醯胺功能去水而轉為腈功能。此反應條件含將該一級羧醯胺與1莫耳當量以上三氟乙酐及2莫耳當量以上吡啶，於如二鸣烷之適當溶劑，於6 0〜1 2 G °C下進行反應。式（Iq: B，D為H，鹵素，CN, C^e烷基，芳基，芳烷基，硝基；X為H，齒素，Ci_6烷基，CN，低全氟烷基，C ^ 6烷氧基，芳烷氧基，硝基，C i - 6烷磺醱基，芳磺醯基，吡啶磺_基，2-N，N-二甲胺乙磺醯基；Y為 H，C 1 , Br , OR 1 ，SR 1 ，NR 1 R 2 ,其中 R1 ，R2 為 H ，Cb6烷基，芳基，或芳烷基；W為CN;RS為H，Ci-e 烷基，芳烷基，芳基，C Η 2 ( 1 Η -眯唑-4 -基），C Η 2 (3 — 1 Η - Β5Ι »朵），CH 2 CH 2 ( 1， 3 -二氧一1， 3 — 二氫一異 »引 B朵一2 -基）,C Η 2 C Η 2 ( 1 -氣一 1， 3 — 二氯一異咐 Β朵一2 -基），C Η 2 ( 3 -哦啶基）；Ε為S或0 )之睛可轉為式（I q ·· Β， D為H，鹵素，CN，烷基，芳基，芳烷基，硝基； X為H，_素，Ci_-6烷基，CN，低全氟烷基，Cre烷氣基，芳烷氯基，硝基，烷磺醯基，芳磺醯基，BH; -56- ------------------- —訂---------線 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 B7_ 五、發明說明（Π ) 啶磺醯基，2 - N，N -二甲胺乙磺醯基；Y為Η，C 1，B r， 0 R 1 ，S R. 1 ，N R 1 R, 2，其中 R 1 ，R 2 為 Η， C 1 - 6 烷基，芳基，或芳烷基；W為5 -四唑；R 5為Η，C i - 6烷基，芳烷基，芳基，C Η 2 ( 1 Η -時 _ - 4 -基），C Η 2 ( 3 - 1. Η -》引 II 朵），C Η 2 C Η 2 ( 1， 3 -二氧- 1， 3 -二氫-異吲 8 朵-2 -基），C Η 2 C Η 2 ( 1 -氧-1，3 '二氫-異蚓 B朵-2 -基），C Η 2 ( 3- 峨啶基）；£為S或0)之四睥，含將腈功能與以1莫耳當量以上三甲胺及1莫耳當量以上三甲矽烷疊氮，於如苯或甲苯之適雷溶劑，於6 0〜1 2 (TC下進行反應。此外，可將腈功能與以1莫耳當量以上銨疊氮，於如二甲基甲醯胺之適當溶劑，於6 Q〜1 6 Q °C下進行反應。反應流程1 〇Rs is H, Ci-6 alkyl, aralkyl, aryl, CH2 (1H-fluorene 4-yl), CH 2 (in the case of 3-1H-H5I), CH 2 CH 2 (1, 3-two gas one 1, 3 — Dichloro-isoco | B-Duo-2 —yl), CH 2 CH 2 (1 -Gas buried 1, 3 —dichloro-isoindole-2 -yl), C Η 2 (3 -pyridine Pyridyl); E is S or O) carboxylic acid amidoamine can be converted into its formula (Iq: B, D is fluorene, halogen, CN, Ci-e alkyl, aryl, aralkyl, nitro · , X cow is H, halogen, Ci-6 alkyl, CN, low perfluoroalkyl, Ci-e alkane group, aralkyl group, nitro group, -55- This paper size applies to Chinese National Standard (CNS) A4 size (210 X 297 mm) (Please read the precautions on the back before filling out this page) '^ w ____ Order --------- line-Printed by a consumer cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 _B7_ V. Description of the Invention (M) Alkylsulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; Y is fluorene, C1, Br, 0R 1, SR 1 , NR 1 R2, where R1, R2 are H, Ch 6 alkyl, aryl, or aralkyl; W is CN; RS is H, (U-6 alkyl, aralkyl, aryl, CH2 (1H -Sleep One 4 -Base , CH 2 (3—1 Η-B), CH 2 C Η 2 (1, 3 -dioxo-1, 3-dichloro-isoβ), β 2 -yl), CH 2 CH 2 (1-oxo-1,3-dihydro-isoindo-8- 2 -yl), C Η 2 (3-amidinyl); E is S or 0) nitrile, which uses reagents The amine function is dehydrated and converted to a nitrile function. The reaction conditions include the first-order carboxyamidamine and 1 mol equivalent of trifluoroacetic anhydride and 2 mol equivalent of pyridine in a suitable solvent such as dioxane at 60. The reaction is performed at ~ 1 2 G ° C. Formula (Iq: B, D is H, halogen, CN, C ^ e alkyl, aryl, aralkyl, nitro; X is H, dentin, Ci_6 alkyl , CN, lower perfluoroalkyl, C ^ 6alkoxy, aralkyloxy, nitro, Ci-6 alkylsulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-di Methylamine ethylsulfonyl; Y is H, C1, Br, OR1, SR1, NR1R2, where R1, R2 are H, Cb6 alkyl, aryl, or aralkyl; W is CN; RS is H, Ci-e alkyl, aralkyl, aryl, C Η 2 (1 Η -oxazole-4 -yl), C Η 2 (3-1 Η-Β5Ι »朵), CH 2 CH 2 (1, 3-Dioxo 1, 3 — Dihydro-iso-synthesis »Introduction to B-C2 2 -C), C Η 2 C Η 2 (1-Ga-1, 3 — Dichloro-Ci-C to B-C 2 -C) Group); E is S or 0) can be converted to the formula (I q · · B, D is H, halogen, CN, alkyl, aryl, aralkyl, nitro; X is H, _ prime, Ci_-6 alkyl, CN, lower perfluoroalkyl, Cre alkyl, aralkyl chloride, nitro, alkanesulfonyl, arylenesulfonyl, BH; -56- -------- ----------- --Order --------- line (Please read the precautions on the back before filling this page) This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) 510900 A7 B7_ V. Description of the invention (Π) Pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; Y is pyrene, C 1, B r, 0 R 1, S R 1, NR 1 R, 2, where R 1 and R 2 are fluorene, C 1-6 alkyl, aryl, or aralkyl; W is 5-tetrazole; R 5 is fluorene, C i-6 alkane , Aralkyl, aryl, C Η 2 (1 Η -hr_-4 -yl), C Η 2 (3-1. Η-"introduction II), C Η 2 C Η 2 (1, 3 -Dioxo- 1, 3 -dihydro-isoindo-8- (2-yl), C Η 2 C Η 2 (1 -oxy-1,3 ' Dihydro-iso earthworm B-2 -yl), C Η 2 (3-eridinyl); 睥 is S or 0) tetrahydrofuran, containing the nitrile function and trimethylamine and 1 mol equivalent The trimethylsilazide above the ear equivalent is reacted in a suitable solvent such as benzene or toluene at 60 ~ 12 (TC). In addition, the nitrile function can be reacted with ammonium azide in an amount of 1 mole equivalent or more in a suitable solvent such as dimethylformamide at 6 Q to 1 6 Q ° C. Reaction Scheme 1 〇

尸4Corpse 4

經濟部智慧財產局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁)Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs (Please read the precautions on the back before filling this page)

反應流程1 〇中其它式（I)化合物衍生梭（可依下法製得。式（I r : B，D為Η，鹵素，C N，C i - 6烷基，芳基，芳烷基，硝基；X為H，鹵素，C i - 6烷基，C N，低全氟烷基，C i - 6烷氧基，芳烷氧基，硝基，C i - 6烷磺醯基，芳磺鶸基，吡〖淀磺醯基，2 - N，N -二甲胺乙磺醯基；Y - 5 7 _ 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 B7 五、發明說明（4) 為 Η， C 1， Br , OR 1 ， SR 1 ， NR1 R 2 ,其中 R 1 ，R, 2 為 (請先閱讀背面之注意事項再填寫本頁) H , C p 6烷基，芳基，或芳烷基；E為S或0)酚可與1 莫耳當量以上雙三甲矽烷醯胺鋰，於-7 8〜室溫下反應，再將鋰鹽與1莫耳當量以上5 -溴瞎脞啶-2 , 4 -二酮（依Derivatives of other compounds of formula (I) in Reaction Scheme 10 (can be prepared according to the following method. Formula (I r: B, D is fluorene, halogen, CN, Ci-6 alkyl, aryl, aralkyl, nitrate X is H, halogen, Ci-6 alkyl, CN, lower perfluoroalkyl, Ci-6 alkoxy, aralkyloxy, nitro, Ci-6 alkylsulfonyl, arylsulfonyl Fluorenyl, pyridine [Yodosulfonyl, 2-N, N-dimethylamine ethylsulfonyl; Y-5 7 _ This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 510900 A7 B7 V. Description of the invention (4) is Η, C 1, Br, OR 1, SR 1, NR1 R 2, where R 1, R, 2 are (Please read the precautions on the back before filling this page) H, C p 6 alkyl, aryl, or aralkyl; E is S or 0) Phenol can react with 1 mol equivalent of lithium bistrimethylsilylamine, at a temperature of -7 ~ 8 ~ room temperature, and then the lithium salt with 1 5-bromopyridine-2, 4-dione (Moore's equivalent)

Zask 等人，J . Med . C h e ϊπ , 1 9 9 0， 33，1 4 1 8 - 1 4 2 3 13 得），使用如Τ fi F之適當溶劑，於惰氣及-7 8〜室溫下進行反應，可得式（I s : R 4為（R 5 S) - 5 -瞎_啶-2，4- 二_ ; B，D為Η，_素，C N，C i - e烷基，芳基，芳烷基 ,硝基；X為Η，_素，C i - 6烷基，C N ,低全氟烷基， C 1 - 6烷氧基，芳烷氧基，硝基，C i ^烷磺醯基，芳磺醯基，Bit啶磺醯基，2 - N，N -二甲胺乙磺醯基；Y為Η， C] 3 R r，OR 1 ， SR 1 ，N R 1 R 2 ,其中 R 1 ，R 2 為 H， C卜6烷基，芳基，或芳烷基；E為S或0)化合物。此外，式（I q : B，D為Η，腐素，C N，C 1 - e烷基，芳基，芳烷基，硝基；X為Η，鹵素，C i - 6烷基，C N，低全氟烷基，C i - 6烷氧基，芳烷氧基，硝基，C i - 6烷磺醯基，芳磺醯基，毗啶磺醯基，2 - N，N -二甲胺乙磺醯基 ;Y 為 H, C]， Br ? 0R 1 ， SR 1 ， NR 1 R 2 ,其中 R 1 ，經濟部智慧財產局員工消費合作社印製 R 2為Η，C p e烷基，芳基，或芳烷基；E為S或0 )酚可依 J u W * P e r i c h 及 R ·，B . Johns, Synthesis, 1 9 8 8, 1 4 2 - 1 4 4 )方法，與】莫耳當量以上含四睡及N，N -二乙胺磷酸二等三丁酯之T fl F於室溫下反應，再於-4 0°C下加入1莫耳當量以上間氯苄酸，可得式（Is:R4為P(0)(0tBu)2 ;B , D為H，_素，C N，C 1 - 6院基，芳基，芳院基，硝 -58- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 經濟部智慧財產局員工消費合作社印製 A7 B7_ 五、發明說明（β) 基；X為H _素，C 烷基，CN，低全氟烷基，C卜6 烷氧基，芳烷氧基，硝基，C - 6烷磺醯基，芳磺醯基 ,毗啶磺醯基，2 - N，N -二甲胺乙磺醯基；Y為Η，C: 1，Zask et al., J. Med. C he ϊπ, 199 0, 33, 1 4 1 8-1 4 2 3 13), using an appropriate solvent such as T fi F, in an inert gas and -7 8 ~ chamber The reaction is carried out at room temperature to obtain the formula (I s: R 4 is (R 5 S)-5 -blind_pyridin-2,4-di_; B, D is fluorene, _ prime, CN, C i-e alkane Group, aryl group, aralkyl group, nitro group; X is fluorene, oxo, C i-6 alkyl group, CN, lower perfluoroalkyl group, C 1-6 alkoxy group, aralkoxy group, nitro group, C i ^ alkylsulfonyl, arylsulfonyl, Bitpyridinsulfonyl, 2 -N, N -dimethylamine ethylsulfonyl; Y is fluorene, C] 3 R r, OR 1, SR 1, NR 1 R 2, wherein R 1 and R 2 are H, C 6 alkyl, aryl, or aralkyl; E is S or 0). In addition, the formula (I q: B, D is fluorene, putrescine, CN, C 1 -e alkyl, aryl, aralkyl, nitro; X is fluorene, halogen, C 6 -alkyl, CN, Low perfluoroalkyl, Ci-6 alkoxy, aralkyloxy, nitro, Ci-6 alkanesulfonyl, arylenesulfonyl, pyridinsulfonyl, 2-N, N-dimethyl Amine ethylsulfonyl; Y is H, C], Br? 0R 1, SR 1, NR 1 R 2, where R 1 is printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, R 2 is fluorene, C pe alkyl, Aryl, or aralkyl; E is S or 0) Phenol can be determined according to Ju W * Perich and R ·, B. Johns, Synthesis, 1 9 8 8, 1 4 2-1 4 4) method, and] T fl F containing four sleeps and N, N-diethylamine phosphate second-class tributyl ester above the molar equivalent is reacted at room temperature, and then 1 mol equivalent of m-chlorobenzyl acid is added at -40 ° C. Available formula (Is: R4 is P (0) (0tBu) 2; B, D are H, _ prime, CN, C 1-6 courtyard, aryl, aromatic courtyard, nitrate -58- this paper size applies China National Standard (CNS) A4 Specification (210 X 297 mm) 510900 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7_ 5. Description of Invention (β) Base; X H _ prime, C alkyl, CN, lower perfluoroalkyl, C6 alkoxy, aralkoxy, nitro, C-6 alkylsulfonyl, arylsulfonyl, pyridinsulfonyl, 2-N, N-dimethylamine ethanesulfonyl; Y is fluorene, C: 1,

Br, OR 1 ， SR 1 ，NR1 R 2 ,其中 R 1 5 R 2 為 H，C i-6 烷基，芳基，或芳烷基；E為S或0)磷酸二酯。此磷酸二酷可處理以1莫耳當量以上氫溴酸之如二鸣烷之適當溶劑，而得式（Ϊ s : R 4 為 P ( () ) ( 0 t B u ) 2 ; B，D 為 Η，鹵素，C Ν，C卜e烷基，芳基，芳烷基，硝基；X為Η，鹵素，C ^ 6烷基，C Ν，低全氟烷基，C i - 6烷氧基，芳烷氧基，硝基，C i - 6烷磺醯基，芳磺醯基，Btt啶磺醯基， 2 - S , N -二甲胺乙磺醯基；Y 為 Η， C 1， B r， 0 R 1 ， S R 1 ， N R 1 R 2 ,其中R. 1 ，R 2為H，C丄“烷基，芳基，或芳烷基；E為S或0 )鱗酸。式（Ir·: B，D為Η,鹵素，CN，Ci-e烷基，芳基，芳烷基，硝基；X為Η，痛素，C 6烷基，CN，低全氟烷基9 C i e烷氧基，芳烷氧基，硝基，C i - 6烷磺醯基，芳磺醯基，吡啶磺醯基，2 - N，N -二甲胺乙磺醯基；Y為 H, C1 , Br, OR 1 ， SR 1 , NR 1 R 2 ,其中 R1 ，R2 為 H ，C卜6烷基，芳基，或芳烷基；E為S或0)酚可轉為式（Is: R，4 為 C ( C Η 3 ) 2 C 0 2 Η ; B，D 為 Η，鹵素，C Ν， Ci-e烷基，芳基，芳烷基，硝基；X為Η，痛素，Cps 烷基，C N，低全氟烷基，C i- 6烷氧基，芳烷氧基，硝基，C :1_ - s烷磺醯基，芳磺醯基，吡啶磺醯基，2 - Ν，N -二甲胺乙磺醯基；Y 為 H， C 1， B r，0 R 1 ， S R 1 ， N R 1 R 2 - 59 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 510900 A7 B7 五、發明說明（W ) 其中 R 1 5 R 2為 Η， C i - 6 烷基，芳基，或芳烷基；Ε 為 S或0) 菝酸 ,其傷將酚處理以2 莫耳當量以上固體N a 0 Η 再處理以 1莫耳當量以上1， 1， 1 -二氯-2 ~ 甲基-2 -丙醇四水合物 5 於存在過量丙酮 (其亦作為溶劑 )下進行反 m h 〇式 ( I r ： B， D為 Η，齒素，c Ν， C 1- .6院基，芳基，芳烷基 > 硝基； X為 Η, 鹵素，C 1 - 6 :烷基，CN 低全氟烷基 c ： L- 6 ;烷氧基，芳烷氧基，硝基， C 1 - 6 烷磺醯基，芳磺醯基吡啶磺醯基，2 - N，二甲胺乙磺醯基； Υ為Η ? C 1 B r ， 0R 1 9 SR 1 ，NR 1 R 2 ，其中R 1 ί β 2為Η C 1 、鱗1 6焼基，或芳烷基； Ε為 S或0) 酚可轉為式 ( Is ： R. 4 Η 2 CH 2 ：CO 2 Η ; Β， D為 H，鹵素， CN , C 1 - 6 院基芳基芳烷基，硝基； X為 Η，腐素， C ^ _ - 6 院基， C N ? 低全氟烷基， C 1 -8院氧基，芳烷氧基，硝基， C 1 « 6 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製烷磺醯基，芳磺醯基，吡啶磺醯基，2 - N，N -二甲胺乙磺藏基；Y 為 Η，C 1, B r，0 R 1 ，S R 1 ，N R 1 R 2，其中 R ，R 2為Η，C i - 6烷基，芳基，或芳烷基；E為S或0 )羧酸，其像將酚處理以1莫耳當量以上Θ -丙醯内酯，並處理以1莫耳當量以上第三丁氧化鉀，於如THF之適當溶劑下進行反應。式（I r : B，D為Η，鹵素，C N，C i - 6烷基，芳基，芳烷基5硝基；X為Η，鹵素，C ^ 6烷基，C N，低全氟烷基，C 6烷氧基，芳烷氧基，硝基，C ^ 6烷磺醯基，芳磺薦基，吡啶磺醯基，2 - N，N -二甲胺乙磺醯基；Y為 ~ G 0 -本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 _^_B7_ 五、發明說明（巧） (請先閱讀背面之注意事項再填寫本頁) H, C1 , Br , OR 1 ? OR 1 ， SR 1 ， NR1 R 2 ,其中 R 1 ，R ^ 為H，C - e;烷基，芳基，或芳烷基；E為S或0)酚可處理以式 C Η ( 0 H ) ( R 7 ) C Η 2 C 0 2 R 6 (其中 R 7 為 Η 或 C 丄一 6 烷基；R 6為C 6烷基）之3 -羥基羧酸酯，可得式（I s B，I)為Ιί，_素，C N，C卜s烷基，芳基，芳烷基，硝基 ;X為Η，_素，C i- e烷基，C Ν，低全氟烷基，C卜6烷氧基，芳烷氣基，硝基，C i - 6烷磺醯基，芳磺醯基，吡啶磺醯基，2 1 , N -二甲胺乙磺醯基；Y為Η，C 1 , B r， OR 1 , S R 1 ，NR 1 R 2 ,其中 R 1 , R 2 為 H，C 丄-6 烷基，芳基，或芳烷基；E為S或0 )酯，其偽依M i t s u η o b u反應 (綜逑參考〇y〇 M i t s u η o b u Synthesis, 1 9 8 1 , 1 - 2 7 ) 而進行反應。其它Mitsunobu反應所需共試劑含1莫耳當量以上偶氮二羧酸C i - 6烷基二酯，如偶氮二羧酸二乙酯或偶氮二羧酸二丙酯，及1莫耳當量以上三芳_(如三苯瞵.），於如***，T H F，苯或甲苯之適當溶劑，於 - 2 0 °C〜1 2 CTC下反應。式 C H ( 0 H ) (R 7 ) C Η 2 C 0 2 R 6 (其中 R 7 為 Η 或 C 丄-6 烷基；Br, OR 1, SR 1, NR1 R 2, where R 1 5 R 2 is H, Ci-6 alkyl, aryl, or aralkyl; E is S or 0) phosphodiester. This diphosphoric acid can process a suitable solvent such as dioxane with hydrobromic acid of more than 1 mole equivalent, and obtain the formula (Ϊ s: R 4 is P (()) (0 t B u) 2; B, D Is fluorene, halogen, C N, C alkyl, aryl, aralkyl, nitro; X is fluorene, halogen, C ^ 6 alkyl, C N, lower perfluoroalkyl, Ci-6 alkyl Oxy, aralkyloxy, nitro, Ci-6 alkylsulfonyl, arylsulfonyl, Bttidinesulfonyl, 2-S, N-dimethylamine ethylsulfonyl; Y is fluorene, C 1, B r, 0 R 1, SR 1, NR 1 R 2, wherein R. 1 and R 2 are H, C, “alkyl, aryl, or aralkyl; E is S or 0) linoleic acid. Formula (Ir ·: B, D is fluorene, halogen, CN, Ci-e alkyl, aryl, aralkyl, nitro; X is fluorene, painin, C 6 alkyl, CN, lower perfluoroalkyl 9 C ie alkoxy, aralkoxy, nitro, Ci-6 alkylsulfonyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamine ethylsulfonyl; Y is H, C1, Br, OR1, SR1, NR1R2, where R1, R2 are H, C6 alkyl, aryl, or aralkyl; E is S or 0) Phenol can be converted to the formula ( Is: R, 4 is C (C Η 3) 2 C 0 2 Η; B, D Is fluorene, halogen, CN, Ci-e alkyl, aryl, aralkyl, nitro; X is fluorene, painin, Cps alkyl, CN, lower perfluoroalkyl, Ci-6 alkoxy , Aralkyloxy, nitro, C: 1_-s-alkanesulfenyl, arylsulfonyl, pyridylsulfonyl, 2-N, N-dimethylamineethanesulfonyl; Y is H, C 1, B r, 0 R 1, SR 1, NR 1 R 2-59-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) -------------- ------ Order --------- line (please read the notes on the back before filling this page) 510900 A7 B7 V. Description of the invention (W) where R 1 5 R 2 is Η, C i-6 alkyl, aryl, or aralkyl; E is S or 0) acetic acid, which treats phenol with 2 mole equivalents or more of solid N a 0 Η and then treats with 1 mole equivalent or more 1, 1 , 1 -dichloro-2 ~ methyl-2 -propanol tetrahydrate 5 inverse mh in the presence of excess acetone (which also serves as a solvent) 〇 formula (Ir: B, D is Η, dentition, c Ν , C 1- .6 alkyl, aryl, aralkyl >nitro; X is fluorene, halogen, C 1-6: alkane , CN low perfluoroalkyl c: L-6; alkoxy, aralkyloxy, nitro, C 1-6 alkanesulfonyl, arylsulfonylpyridinesulfonyl, 2 -N, dimethyl Amine ethylsulfonyl; Υ is Η? C 1 B r, 0R 1 9 SR 1, NR 1 R 2, where R 1 β β 2 is Η C 1, phosphonium 16 fluorenyl, or aralkyl; Ε is S or 0) Phenol can be converted to the formula (Is: R. 4 Η 2 CH 2: CO 2 Η; B, D is H, halogen, CN, C 1-6 alkylarylaralkyl, nitro; X For fluorene, putresin, C ^ _-6 courtyard, CN? Low perfluoroalkyl, C 1 -8 courtyard oxygen, aralkoxy, nitro, C 1 «6 (Please read the notes on the back first (Fill in this page again.) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. , B r, 0 R 1, SR 1, NR 1 R 2, where R and R 2 are fluorene, Ci-6 alkyl, aryl, or aralkyl; E is S or 0) a carboxylic acid, like Treatment of phenol with 1 mol equivalent or more Θ-propiolactone, and treatment with 1 mol equivalent or more of third butoxylate Potassium is reacted in a suitable solvent such as THF. Formula (I r: B, D is fluorene, halogen, CN, Ci-6 alkyl, aryl, aralkyl 5nitro; X is fluorene, halogen, C ^ 6 alkyl, CN, lower perfluoroalkane Group, C 6 alkoxy group, aralkoxy group, nitro group, C ^ 6 alkanesulfonyl group, arylsulfonyl group, pyridylsulfonyl group, 2-N, N-dimethylamine ethylsulfonyl group; Y is ~ G 0-This paper size is in accordance with China National Standard (CNS) A4 (210 X 297 mm) 510900 A7 _ ^ _ B7_ V. Description of the invention (Clever) (Please read the notes on the back before filling this page) H, C1, Br, OR 1? OR 1, SR 1, NR1 R 2, where R 1, R ^ are H, C-e; alkyl, aryl, or aralkyl; E is S or 0) Phenol can be treated A 3-hydroxycarboxylic acid ester of formula CΗ (0H) (R7) C C2C02R6 (where R7 is Η or C 丄 6 alkyl; R6 is C6 alkyl), It can be obtained that the formula (Is B, I) is Ι, _ prime, CN, C, alkyl, aryl, aralkyl, nitro; X is fluorene, _ prime, Ci-e alkyl, C Ν , Lower perfluoroalkyl, C6alkoxy, aralkylamino, nitro, Ci-6 alkylsulfonyl, arylsulfonyl, pyridylsulfonyl, 2 1, N-dimethylamine ethyl Sulfonyl; Y is fluorene , C 1, B r, OR 1, SR 1, NR 1 R 2, where R 1, R 2 are H, C 丄 -6 alkyl, aryl, or aralkyl; E is S or 0) ester, Its pseudo-reaction is carried out according to M itsu η obu reaction (refer to 〇y〇M itsu η obu Synthesis, 198 1, 1-2 7). Other co-reagents required for Mitsunobu reaction contain more than 1 mole equivalent of Ci-6 alkyl diester of azodicarboxylic acid, such as diethyl azodicarboxylate or dipropyl azodicarboxylate, and 1 mole The equivalent of the above triaryl compound (such as triphenylhydrazone) is reacted in a suitable solvent such as diethyl ether, THF, benzene or toluene at -20 ° C ~ 1 2 CTC. Formula C H (0 H) (R 7) C Η 2 C 0 2 R 6 (where R 7 is Η or C 丄 -6 alkyl;

I 3 之基院 6 - 1 C 為 6 R 由可或得可售市為酯酸駿經濟部智慧財產局員工消費合作社印製得製法方準標依物前酸羧得可售市式 S I—_ 素 0The base of I 3 6-1 C is 6 R It is printed by Cocoa or Cocoa for sale in the market. It is printed by the company ’s Consumer Property Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. _ Prime 0

Ν CΝ C

1 C 芳基烷芳 UH ，為基 X氣 :烷基 8 硝 , 1 ， C 棊烷基磺芳 Η 素鹵氧烷芳基，烷基 S 硝烷氟全氐 /1 醯磺烷 - 2 基醯磺啶 αβ WP 4J、:T 茅醯磺乙胺甲為 Υ R 01 C arylalkaryl UH, as the radical X gas: alkyl 8 nitrate, 1, C, alkylsulfonyl haloxane haloxane aryl, alkyl S nitryl fluoroperfluorene / 1 sulfonane-2 Sulfapyridine αβ WP 4J 、: T

R S R ΝR S R Ν

2 R R 中其2 R R in which

Η 為 2 R 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 B7_ 五、發明說明（k ) (請先閱讀背面之注意事項再填寫本頁) ,Ci-e烷基，芳基，或芳烷基；E為S或0)酯可轉為式（I s : R 4 為（R ) - C H ( R 7 ) C Η 2 C 0 2 Η ; B，D 為 Η，鹵素 ,C Ν，C卜s烷基，芳基，芳烷基，硝基；X為Η，鹵素，C卜6烷基，C Ν ,低全氟烷基，C - 6烷氧基，芳烷氧基，硝基，C ^ e烷磺醯基，芳磺醯基，吡旋磺醯基， 2 - N， N -二甲胺乙磺醯基；Y 為 Η， C 1 , B r，0 R 1 ， S R 1 ，N R 1 R, 2，其中R 1 ，R 2為Η , C丄一 6烷基，芳基，或芳烷基；E為S或0)酸，其可使用數個標準方法含將（Is) 酯與1莫耳當量以上礦物酸（如H C 1或硫酸），於一以上溶劑或二者以上溶劑（如水，T H F或二Blf烷）之組合，於4 0〜1 2 0 °C下反應。此外，上述式（I s )酯轉為酯之反應亦可使用其它方法。含將式（I s )酯與1莫耳當量以上三溴化硼或三氯化之二氯甲烷，於-7 8 °C〜室溫之下反應；與於乙酸之2莫耳當量以上氫溴酸於（}〜5 0 °C 下反應；與含2莫耳當量以上三甲矽烷溴或三甲矽烷碘之二氯甲烷，四氯化碳或乙腈，於-7 8〜5 0 3C下反應；與含2莫耳當量以上碘化鋰之吡啶或陛啉，於6 0〜2 5 0 °C 下反應。式（Ir: B為N02 ; D為Η或Br; X為H,鹵素，Ci-6烷經濟部智慧財產局員工消費合作社印製基，CN，低過氟烷基，C^6烷氧基，芳烷氧基，硝基， Ct-8烷磺_基，芳磺醯基，毗啶磺釀基，2-N，N -二甲胺乙磺醯基；Y為0 R, 1 ， S R 1 , N R 1 R 2，其中R. 1 ， R 2為H，c :1. _ 6烷基，芳基，或芳烷基；E為S或0 )硝酚可烷化以1莫耳當景以上烷基或式（X R 4，其中X為C 1 , -6 2 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 經濟部智慧財產局員工消費合作社印製 A7 B7_ 五、發明說明（^ ) B r，或I見R4-C:L-6烷基，芳烷基）芳烷痛，及1莫耳當量以上鹼金屬碳酸鹽（如碳酸鉀），於極性非質子溶劑如D M F反應可得式（I s : B為N 0 2 ; D為Η或B r ; X為Η， _素，Ci-6烷基，CN，低全氟烷基，Ci_6烷氧基，芳烷氧基，硝基，C i s烷磺醯基，芳磺醯基，吡啶磺醯基，2 - N , N -二甲胺乙磺酸基；Y為Η，0 R 1 ， S R 1 ， N R 1 R 2，其中R 1 , R 2為η , C 1 - 6烷基，芳基，或芳烷基；E為S或0; ^為^·^烷基，芳烷基）之烷化物。式（I s : B為NO 2 ; D為Η或Br ; X為Η，鹵素，C卜6烷基，C Ν，低過氟烷基，C 1 - 6烷氧基，芳烷氧基，硝基 ,C χ - 6烷磺醻基，芳磺醯基，毗啶磺醯基，H Ν -二甲胺乙磺醯基；Y為Η 5 0 R 1 ， S R 1 ， N R 1 R 2 ,其中R 1 ,R 2為Η，C i - 6烷基，芳基，或芳烷基；Ε為S或0 ; R 4為C卜8烷基，芳烷基）之硝化合物可還原得式（I s : B為NH 2 ; D為Η或Br ; X為Η，鹵素，C卜6烷基，CN，低 —t氟烷基，Ci-e烷氧基，芳烷氧基，硝基，Ci-6烷磺基，芳磺鶸基s吡啶磺醯基，2-N，N -二甲胺乙磺醯基；Y為 0 R 1 s SR 1 , NR1 R 2 ,其中 R1 5 R2 為 H， Ci-6烷基，芳基，或芳烷基；E為S或0; R4為烷棊，芳烷基）之胺化合物，傷使用含二氯化錫之乙酸乙 _，於4 Π〜1 0 (TC下反應，或與阱及蒙脫土之乙醇，於 4 0〜1 0 ITC下反應。式（I s : Β為N H 2 ; D為Η或B r ; X為Η，痛素，C 1 - 6烷基，C Ν，低過氟院基，C 1 - ο院氣基，芳院氧基，5®基 -63- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 510900 A7 _B7___ 五、發明說明（^) 9 β 1 - 8綜磺II基，芳磺醯基，1¾ 鑛醯基，2 - N，N -二甲胺乙磺醱基；Y為Η， 0 R 1 , S R 1 ， N R 1 R 2 ，其中R i (請先閱讀背面之注意事項再填寫本頁) s R 2為Η , c 1 - 6烷基，芳基，或芳烷基；Ε為S或0 ; R 4為c卜e烷基，芳烷基）之胺化合物可烷化以1莫耳Η is 2 R This paper size applies Chinese National Standard (CNS) A4 specification (210 X 297 mm) 510900 A7 B7_ V. Description of invention (k) (Please read the precautions on the back before filling this page), Ci-e Alkyl, aryl, or aralkyl; E is S or 0) Ester can be converted to formula (I s: R 4 is (R)-CH (R 7) C Η 2 C 0 2 Η; B, D are Fluorene, halogen, C N, C alkyl, aryl, aralkyl, nitro; X is fluorene, halogen, C alkyl, C NH, lower perfluoroalkyl, C-6 alkoxy , Aralkyloxy, nitro, C ^ e alkylsulfonyl, arylenesulfonyl, pyridosulfonyl, 2-N, N-dimethylamine ethylsulfonyl; Y is fluorene, C 1, B r, 0 R 1, SR 1, NR 1 R, 2, where R 1, R 2 are Η, C 丄 -6 alkyl, aryl, or aralkyl; E is S or 0) acid, which can be used Several standard methods involve combining (Is) esters with more than 1 mol equivalent of mineral acid (such as HC 1 or sulfuric acid) in one or more solvents or two or more solvents (such as water, THF, or di-Blf alkane) at 40 Reaction at ~ 120 ° C. In addition, the above-mentioned reaction for converting the ester of the formula (Is) to an ester may use other methods. Contains the reaction of an ester of formula (Is) with more than 1 mole equivalent of boron tribromide or dichloromethane in dichloromethane at -78 ° C ~ room temperature; and more than 2 mole equivalents of hydrogen in acetic acid Bromic acid reacts at () ~ 50 ° C; reacts with dichloromethane, carbon tetrachloride, or acetonitrile containing more than 2 mol equivalents of trimethylsilyl bromide or trimethylsilyl iodide, at -78 to 5 0 3C; Reacts with pyridine or oxoline containing lithium iodide above 2 mole equivalents at 60 ~ 250 ° C. Formula (Ir: B is N02; D is osmium or Br; X is H, halogen, Ci- Printed base of the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, CN, low perfluoroalkyl, C ^ 6 alkoxy, aralkyloxy, nitro, Ct-8 alkylsulfonyl, arylsulfonyl, Pyrimidinesulfonyl, 2-N, N -dimethylamine ethylsulfonyl; Y is 0 R, 1, SR 1, NR 1 R 2 where R. 1, R 2 is H, c: 1. _ 6 alkyl, aryl, or aralkyl; E is S or 0) Nitrophenol can be alkylated to 1 mole or more alkyl or formula (XR 4, where X is C 1, -6 2-this paper Standards apply to China National Standard (CNS) A4 specifications (210 X 297 mm) 510900 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs Preparation of A7 B7_ 5. Description of the invention (^) B r, or I see R4-C: L-6 alkyl, aralkyl) arane pain, and alkali metal carbonates (such as potassium carbonate) of more than 1 mole equivalent, In a polar aprotic solvent such as DMF, formula (I s: B is N 0 2; D is Η or B r; X is Η, _ prime, Ci-6 alkyl, CN, low perfluoroalkyl, Ci_6 Alkoxy, aralkoxy, nitro, C is alkylsulfonyl, arylenesulfonyl, pyridylsulfonyl, 2-N, N-dimethylamineethanesulfonate; Y is fluorene, 0 R 1 , SR 1, NR 1 R 2, where R 1, R 2 are η, C 1-6 alkyl, aryl, or aralkyl; E is S or 0; ^ is ^ · ^ alkyl, aralkyl Alkoxides of the formula: (I s: B is NO 2; D is thorium or Br; X is thorium, halogen, C 6 alkyl, C N, lower perfluoroalkyl, C 1-6 alkoxy, Aralkyloxy, nitro, C χ-6 alkanesulfonyl, arylenesulfonyl, pyridinsulfonyl, H Ν -dimethylamine ethylsulfonyl; Y is Η 5 0 R 1, SR 1, NR 1 R 2, wherein R 1 and R 2 are pyrene, Ci-6 alkyl, aryl, or aralkyl; E is S or 0; R 4 is C8 alkyl, aralkyl) The compound can be reduced to formula (I s: B is NH 2; D is fluorene or Br; X is fluorene, halogen, C6 alkyl, CN, low-tfluoroalkyl, Ci-e alkoxy, aralkoxy, nitro, Ci-6 alkylsulfo, aromatic Sulfonylspyridinesulfonyl, 2-N, N-dimethylamine ethylsulfonyl; Y is 0 R 1 s SR 1, NR1 R 2, where R1 5 R2 is H, Ci-6 alkyl, aromatic Group, or aralkyl group; E is S or 0; R4 is alkane, aralkyl) amine compound, using ethyl acetate containing tin dichloride, reaction at 4 Π ~ 1 0 (TC, or Reacts with well and montmorillonite ethanol at 40 ~ 10 ITC. Formula (I s: Β is NH 2; D is Η or B r; X is 痛, analgesin, C 1-6 alkyl, C Ν, low perfluorinated radical, C 1-ο radical gas radical, Fangyuan Oxygen-based, 5®-63- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) -------------------- Order- -------- Line (Please read the notes on the back before filling this page) 510900 A7 _B7___ V. Description of the invention (^) 9 β 1-8 Comprehensive sulfonyl II, arylsulfonyl, 1¾ , 2-N, N-dimethylamine ethylsulfonyl; Y is fluorene, 0 R 1, SR 1, NR 1 R 2, where R i (please read the precautions on the back before filling this page) s R 2 is fluorene, c 1-6 alkyl, aryl, or aralkyl; E is S or 0; R 4 is c alkyl, aralkyl) amine compound can be alkylated to 1 mole

當量以上如式（X2CHR6aC〇2#，其中X2為Cl5 Br,或I 且R 6為C i - e;烷基，Rba為H)鹵乙醇烷酯，且與】莫耳當Μ以上_金屬磺酸鹽（如磺酸鉀），於極性非質子溶麵如DM下反應，可得式（Ts:B為NCHR6ac〇2R6 ; r e為 6 a c 1 - e烷基，R 為Η或Ci-6烷基；D為Η或Br; X為Η, ® 素^ C 1 - ο烷基，C Ν，低全氟院基s C 1 - e院氧基，芳院氧基，硝基^ Ci-6烷磺醯基，芳磺基，毗啶磺醯基， 2 - N s N -二申胺乙磺醯基；γ為 h，OR1 ，SR1 ，NR1 R2 ,其中R 1 , R 2為Η ，C !一 6烷基，芳基，或芳烷基； Ε為S或0 ; R *為C ρ 6烷基，芳烷基）之烷化物。此酯可依檫準方法轉為其羧酸而得式（Is:B為NCHR6aC〇2H; R.為Η或C i_ - 6烷基；I)為Η或B r ; X為Η，鹵素，C ；l - 6烷基，C N，低全氟烷基，c i s烷氧基，芳烷氯基，硝基，醯磺烷醯磺芳基醯磺啶吼經濟部智慧財產局員工消費合作社印制衣The above equivalent is as shown in the formula (X2CHR6aC〇2 #, where X2 is Cl5 Br, or I and R 6 is C i-e; alkyl, Rba is H) haloethanol alkyl ester, and with] more than M _ metal sulfonate Acid salt (such as potassium sulfonate), reacted on a polar aprotic surface such as DM to obtain the formula (Ts: B is NCHR6ac〇2R6; re is 6 ac 1-e alkyl, R is fluorene or Ci-6 alkane D is fluorene or Br; X is Η, ® ^ C 1-ο alkyl, C Ν, low perfluorinated s C 1-e oxo, aryl oxo, nitro ^ Ci-6 Alkylsulfonyl, arylsulfonyl, pyridinsulfonyl, 2-N s N-dishenamine ethylsulfonyl; γ is h, OR1, SR1, NR1 R2, where R1, R2 are fluorene, C -A-6 alkyl, aryl, or aralkyl; E is S or 0; R * is an alkylate of C ρ 6 alkyl, aralkyl). This ester can be converted to its carboxylic acid according to the standard method (Is: B is NCHR6aCO2H; R. is fluorene or Ci-6 alkyl; I) is fluorene or Br; X is fluorene, halogen, C; l-6 alkyl, CN, low perfluoroalkyl, cis alkoxy, aralkyl chloride, nitro, sulfonane sulfonyl sulfonyl sulfonium clothes

醱磺乙黑 2 胺 R Η酦 Sulfaethylene black 2 amine R Η

1 C 為烷 Υ 6 Η 基烷如芳上，以基鼉烷當〇〇耳 1 莫液如混劑之 Η Τ R ο1 C is an alkyl alkane, such as aryl, and an alkyl alkoxide is used as a molar solution, such as 之 Τ R ο

R SR S

R N 基烷芳或基R N group alkaryl or radical

N 其或 1 S 2 > L— 為， 2 E R 甲 R 中 οN or 1 S 2 > L— is, 2 E R in R

為 4 R Η ο οα 含用溶使共中與其，液水溶之水物用化使氣含氫〇屬酸金羧鹼之之醇甲〇如應 ί 反醇下烴之低°c 或40 烷 ~ 咢 C RH 0 二 ο -於及 F Η Τ 或酉烴 4 8 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 B7It is 4 R Η ο οα Contains the solvent to dissolve it, and the water-soluble water is used to make the gas hydrogen. The alcohol is an acid gold carboxy base. The alcohol is a low ° c or 40 alkane under the alcohol. ~ 咢 C RH 0 二 ο-Yu and F Τ or 酉 hydrocarbon 4 8 This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) 510900 A7 B7

五、發明說明（W ) 反應流程1 1V. Description of the Invention (W) Reaction Scheme 1 1

反應流程1 1中其它式（I)化合物衍生物可依下法製得。式（I t : B，I)為Η，鹵素，C N，C i - 6烷基，芳基，芳烷基，硝基；X為Η，_素，C i s烷基，c N，低全氟烷基，C i 6烷氧基，芳烷氧基，硝基；γ為c 1，b r，〇 r 1 ，其中R1 ，R2為|{，Ci-6院基，芳基，或芳院基；Rs 為Η，C 1 - 6烷基，芳基或芳烷基；R 6為u，c i - 6烷基）化合物可轉為式（lu: n=l ; B，D為H，齒素，CN，C卜6 烷基，芳基，芳烷基，硝基；X為Η，鹵素，C i胃6烷基， C N，低全氟烷基，C p e烷氣基，芳烷氧基，硝基；¥為 C]，Br，OR 1，其中R i , R2為h，c卜6烷基，芳基，或芳烷基；R s為H，C i - e;烷基，芳基或芳烷基；R 6為 H , C 1 - 6烷基）亞ffi化合物，傺使用1莫耳當量以上如間氯過T酸之氧化劑之二氯甲烷，於_ 2 0〜4 0 °C下反應，或以過乙酸之乙酸及水，於室溫〜1 〇〇汜下反應。式（It: β，Π為H，齒素，CN，Ci-6烷基，芳基，芳本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------^--------- (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印制衣經濟部智慧財產局員工消費合作社印製 510900 A7 B7___ 五、發明說明（W ) 烷基，硝基；X為H，鹵素，C卜6烷基，C N，低全氟烷基，C 1- e烷氧基，芳烷氧基，硝基；Y為C 1，B r，0 R 1 ，其中R 1 , R 2為Η，C i - 6烷基，芳基，或芳烷基； R 5為Η，C i - 6烷基，芳基或芳烷基；R 6為Η，C i - 6烷基）化合物可轉為如式（I u : η = 2 ; B，D為Η，鹵素，C N ，C '1 - 6院基，芳基，芳院基，硝基；X為Η，痛素，C 1 - 6 烷基，C Ν 5低全氟烷基，C ϋ烷氧基，芳烷氧基，硝基；Υ為C 1，B r，0 R 1 ，其中R 1 ，R 2為Η，C卜6烷基，芳基，或芳烷基；R, 5為Η，C卜s烷基，芳基或芳烷基； R 6為Η，C ^ e烷基）δϋ衍生物，傷使用2莫耳當量以上如間氯過苄酸之氧化劑之二氯甲烷，於-2 0〜6 0 °C下反應，或以過乙酸之乙酸及水，於室溫〜1 〇〇 °C下反應。本發明化合物可用以治療與抗胰島素症及高血糖症相關之代謝異常5典型伴隨以肥胖或葡萄糖不耐性。因此 ,本發明化合物尤可用以治療或抑制I I型糖尿病。本發明化合物亦可用以調節於如I型糖尿病異常中葡萄糖之量。本發明化合物用以治療或抑制與抗胰島素症及高血糖症相關之代謝異常之能力傜由本發明化合物，於下列2 個標準藥理試驗法，測量PTP酶抑制作用而完成。上麗」—m— 器+二礤胖版去非磷化夕拙制作用此標準藥理試驗方法可評估鼠肝微小體ρ T P酶活性之抑作用，偽使用相對於1 1 4 2 - 1 1 5 3胰島素受器激酶結構域之磷酪胺酸十二胜駄為受質，其於1 1 4 6， 1 1 5 0及1 1 5 1 -0 6 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 _B7_ 五、發明說明（V ) 酪胺酸磷化。所用方法及所得結果蘭逑如下。製備徵小體：將鼠 y!Sprague-Dawley®(Charles-R. i v e r 3 K i n g s t ο η , N Y ) 5 重 1 0 Q - 1 5 0 克，餵以標準食物 (P u i n a ) ) 5以C 0 2殺死並二側胸廓切開。取出肝，以冷 0 . 8 5 % ( w / v )食鹽水洗並稱重 ο 將組織於冰上以 10倍體積緩衝液 A均質，並依Mey e r 0 V it c h J > R o t h e η be r g P > Sh e c h t e r Y， Bo η n e r -Wei. r S， K a h η CR • Va n a da t e η ο r iri a I i z e S h ：y p erg 1 y c e in i a i η t w 0 ffi 0 us e 10 dels 0 f no n - in s ii 1 i n ~ d e pen d e n t d i a b e t e s m el 1 i t. π s . J C 1 i n I η v e s t 1 9 9 1; 8 7 : 1 2 8 0 - 12 9 4 及 A1 be Ft s B， B r a y D， L· θ w i s J， Raff Μ , R o b e r t s K Wa t s on JD , e di to r s • Mo 1 e C 11 la r bio]. 〇 gy of t he c el 1 B N e w Y or k i G a r la n d Ρπ bl is hi n g , In e ·, 1 9 8 9 方法稍作修飾而分離微小體 ο 將肝均質液濾經絲以除去組織殘渣 j 於 4°C 及 1 0， 0 0 〇g 下離心20分。倒除上清液，於4°C及100，OOOg下離心60 分。將小粒，徹小體及小胞泡懸浮並均質於2 Q毫莫耳 T r i s - H C I ( p Η 7 · 4 )，5 0毫莫耳2 -硫氫乙醇，2 5 0毫莫耳蔗糖，2毫莫耳K D T A , 1 0毫莫耳E G T A，2毫莫耳A E B S F , 0 · 1 毫莫耳T L C K , 0 · 1毫莫耳T P C K，0 · 5毫莫耳苄脒，2 5微毫克/毫升亮肽素，5微毫克/毫升胃蛋白酶抑制素A，5徹毫克/毫升Η 5 B止痛劑，5徼毫克/毫升凝乳抑制素，1 0徹毫克/毫升抑版酶（緩衝液Α)，至終濃度約850微毫克蛋白質/毫升。蛋白質濃度由P i e r c e C ο 〇 m a. s s i e Ρ 111 s P r o t e i n A s s a y ,使用結晶牛血清白蛋白為標準（P i e r c e -8 7 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 x 297公釐） --------------------訂--------- (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7_ 五、發明說明（k )The derivatives of other compounds of formula (I) in Reaction Scheme 11 can be prepared according to the following method. Formula (I t: B, I) is fluorene, halogen, CN, Ci-6 alkyl, aryl, aralkyl, nitro; X is fluorene, _ prime, C is alkyl, c N, low Fluoroalkyl, Ci 6 alkoxy, aralkoxy, nitro; γ is c 1, br, 0r 1, where R1 and R2 are | {, Ci-6, aryl, or aryl Rs is fluorene, C 1-6 alkyl, aryl or aralkyl; R 6 is u, ci-6 alkyl) The compound can be converted to the formula (lu: n = l; B, D is H, and Element, CN, C6 alkyl, aryl, aralkyl, nitro; X is fluorene, halogen, Ci 6 alkyl, CN, low perfluoroalkyl, C pe alkyl, aralkyloxy Group, nitro; ¥ is C], Br, OR 1, wherein R i, R 2 is h, c 6 alkyl, aryl, or aralkyl; R s is H, C i -e; alkyl, Aryl or aralkyl; R 6 is H, C 1-6 alkyl) ffiene compound, 傺 use more than 1 mole equivalent of dichloromethane such as m-chloroper T acid oxidant, _ 2 0 ~ 4 0 Reaction at ° C, or with acetic acid and water at room temperature ~ 100 ° F. Formula (It: β, Π is H, dentin, CN, Ci-6 alkyl, aryl, and aromatic paper sizes are applicable to China National Standard (CNS) A4 specifications (210 X 297 mm) ------- ------------- ^ --------- (Please read the notes on the back before filling out this page) Intellectual Property Bureau, Ministry of Economic Affairs, Consumer Consumption Cooperative, Printing and Manufacturing, Ministry of Economic Affairs, Wisdom Printed by the Consumer Cooperative of the Property Bureau 510900 A7 B7___ V. Description of the invention (W) alkyl, nitro; X is H, halogen, C6 alkyl, CN, low perfluoroalkyl, C1-e alkoxy , Aralkoxy, nitro; Y is C 1, B r, 0 R 1, where R 1, R 2 are fluorene, Ci-6 alkyl, aryl, or aralkyl; R 5 is fluorene, Ci-6 alkyl, aryl or aralkyl; R6 is fluorene, Ci-6 alkyl) compounds can be converted to formula (Iu: η = 2; B, D is fluorene, halogen, CN, C '1-6 alkyl, aryl, aryl, nitro; X is fluorene, analgesic, C 1-6 alkyl, C Ν 5 perfluoroalkyl, C alkoxy, aralkyloxy Group, nitro group; fluorene is C 1, B r, 0 R 1, wherein R 1 and R 2 are fluorene, C 6 alkyl, aryl, or aralkyl; R, 5 is fluorene, C 1 alkane Aryl, aryl or arane R 6 is a fluorene, C ^ e alkyl) δ fluorene derivative, using dichloromethane with an oxidant such as m-chloroperbenzoic acid of more than 2 mole equivalents, and reacting at -20 to 60 ° C, or Peracetic acid and water were reacted at room temperature to 100 ° C. The compounds of the present invention can be used to treat metabolic disorders related to insulin resistance and hyperglycemia 5 typically accompanied by obesity or glucose intolerance. Therefore, the compounds of the present invention are particularly useful for treating or inhibiting type I diabetes. The compounds of the invention can also be used to regulate the amount of glucose in abnormalities such as type I diabetes. The ability of the compound of the present invention to treat or inhibit metabolic abnormalities related to anti-insulinism and hyperglycemia is accomplished by measuring the PTPase inhibitory effect of the compound of the present invention in the following two standard pharmacological tests. "Shangli" —m— organ + Erzhi fat version dephosphorized Xizhuo production This standard pharmacological test method can be used to evaluate the inhibitory effect of rat liver microsome ρ TP enzyme activity, compared with 1 1 4 2-1 1 5 3 Insulin receptor kinase domain phosphotyrosine dodecazone is a substrate, which is used in 1 1 4 6, 1 1 50 and 1 1 5 1 -0 6-This paper size applies Chinese National Standard (CNS ) A4 size (210 X 297 mm) -------------------- Order --------- line (Please read the precautions on the back before (Fill in this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 _B7_ V. Description of the invention (V) Tyrosine phosphorylation. The method used and the results obtained are as follows. Preparation of sign bodies: Rat y! Sprague-Dawley® (Charles-R. Iver 3 Kings ο η, NY) 5 weight 1 0 Q-1 50 g, fed with standard food (P uina) 5 to C 0 2 killed and bilateral thoracotomy. The liver was removed, washed with cold 0.85% (w / v) saline and weighed. The tissue was homogenized on ice with 10 times the volume of buffer A, and according to Meyer 0 V it ch J > R othe η be rg P > Sh echter Y, Bo η ner -Wei. r S, K ah η CR • Va na da te η ο r iri a I ize S h: yp erg 1 yce in iai η tw 0 ffi 0 us e 10 dels 0 f no n-in s ii 1 in ~ de pen dentdiabetesm el 1 i t. π s. JC 1 in I η vest 1 9 9 1; 8 7: 1 2 8 0-12 9 4 and A1 be Ft s B, B ray D, L · θ wis J, Raff Μ, Roberts K Watts on JD, e di to rs • Mo 1 e C 11 la r bio]. 〇gy of t he c el 1 BN ew Y or ki G ar la nd ππ bl is hi ng, In e ·, 1 9 8 9 The method is slightly modified to isolate microsomes. ο Filter the liver homogenate through a wire to remove tissue residues at 4 ° C and 1 0, 0 0 Centrifuge at 0 g for 20 minutes. The supernatant was decanted and centrifuged at 4 ° C and 10,000 g for 60 minutes. Suspend the pellets, corpuscles and vesicles and homogenize them at 2 Q mol Tris-HCI (p Η 7 · 4), 50 mol 2-thiohydroethanol, 250 mol sucrose, 2 millimoles KDTA, 10 millimoles EGTA, 2 millimoles AEBSF, 0.1 millimoles TLCK, 0.1 millimoles TPCK, 0.5 millimoles benzamidine, 25 micromg / ml Leupeptin, 5 μg / ml pepsin A, 5 μg / ml Η 5 B analgesic, 5 μg / ml rennetin, 10 μg / ml platenase (Buffer A) To a final concentration of about 850 micrograms of protein / ml. The protein concentration was determined by Pierce C ο 〇m a. Ssie ρ 111 s Protein A ssay, using crystalline bovine serum albumin as the standard (Pierce -8 7-This paper size applies the Chinese National Standard (CNS) A4 specification (210 x 297 mm) -------------------- Order --------- (Please read the precautions on the back before filling in this page) Ministry of Economy Wisdom Printed by the Consumer Cooperative of the Property Bureau 510900 A7 B7_ V. Description of Invention (k)

Chemical Co" Rockford, I L) 〇測量 P T P 酶活性：使用如 L a n z e 1.1 a P A，A 1 v a r e z L J，Chemical Co " Rockford, I L) 〇 Measure P T P enzyme activity: use such as

R e i ώ a c h P S，如拿大，0 A所述孔雀綠-鉬酸銨方法。使用改良無機磷酸鹽微毫莫耳量分析法於平板計數器（Ana 1 . B i 〇 c h e πϊ . 1 9 7 9 ; 1 0 0 : 9 5 - 9 7 )，以計量由鼠肝微小體 P T P 酶釋放微毫莫耳之磷酸。試驗方法使用由An a S p e c，I n e . (S a η J o s e，C A )合成之十二磷胜販為受質。此胜肽， ΐ R D ΓΥ f: T D Y YR.K,相對於_島素受器催化結構域，為酪胺酸磷化於1 1 4 6 5 U 5 0及1 1 5 1酪胺酸。將此徹小體部份 (8 3 · 2 Fi u 1 )於含或不含試驗化合物（6 β 2 5徹升）及3 0 5 · 5微升之8 1 . 8 3毫莫耳Η P E S反應緩衝液，ρ Η 7 . 4，預培養於3 7 °C 10分。將胜肽受質（10 . 5徹升，終濃度50微莫耳）以具微平板連接器之L A B L I N E Mu 1 t卜B 1 〇 k加熱器調至3 7 °C。加入含或不含試驗化合物之預培養微小體部份（3 9 . 5微升）以起始去磷化反應，於3?°C下30分。加入200徹升孔雀緣-鉬酸銨- Tween20中止劑（MG/AM/Tw)以中止反應。此中止劑含3份0 . 4 5 %孔雀綠鹽酸鹽，1份4 β 2 %鉬酸銨四水合物於 4 N H C 1 及（Κ 5 % T w e e η 2 0。加入 2 0 0 徹升 M G / A M / T w 至受質並加入3ίΚ5微升含或不含試驗化合物之預培養徼小體部份可得對照組。於室溫下呈色5小時，於6 5 0 iim 下使用平板計數器（Μ ο 1 e c u 1 a r D e v i c e s )測量吸光度。準備4個樣本及對照重覆。並測量50微莫耳（終濃度）藥對徹小體PTP酶之抑制作用。計算：基於磷酸評標準曲線，P T P酶活性可以釋放徹毫 -68- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂--------- (請先閱讀背面之注意事項再填寫本頁) 510900 A7 B7 五、發明說明U7 ) 莫耳磷酸鹽/分/毫克蛋白質表示。試驗化合物之ρ Τ P __制作用以相較於對照之百分比而計算^使用由S A S 6 · 0 8版，P R 0 C N L I N之P T P酶活性之四介質非線性對數迴歸可測定試驗化合物之T C 50。所有試驗化合物以5 0微莫耳濃度投予。使用本發明代表化合物可得如下結果。經濟部智慧財產局員工消費合作社印製例從對照之變化％ 9 -49.80 19 -30.40 20 2.13 21 -63.12 22 -28.57 23 -26.11 24 -65.31 29 -83.54 30 -60.32 31 -63.42 32 -89.41 33 -61.92 34 -63.01 35 -58.85 36 •67.00 37 -49.83 38 -57.74 40 -83.88 41 -39.60 42 -63.41 43 -78.84 44 -68.50 45 -94.50 46 -91.00 _ - 47 -68.48 48 -44.69 49 -89.36 50 -81.27 52 -87.66 53 -81.83 苯基氧化砷 (參考標準） -57.06 .69 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) tr---------線_· )1〇9〇〇 A7 B7 五、經濟部智慧財產局員工消費合作社印製發明說明（W) &ji.ptpi b引 ffi η 磷化二磯胖R e i free a c h P S, as described in Nathan, 0 A malachite green-ammonium molybdate method. A modified inorganic phosphate micromolar assay was used in a plate counter (Ana 1. B i 〇che πϊ. 1 799; 1 0: 9 5-9 7) to measure the PTPase from mouse liver microsomes Releases micromolar phosphoric acid. For the test method, twelve phosphorus phosphate synthesized by An a Spec, Ine. (Sa η Jose, CA) was used as the substrate. This peptide, ΐ R D ΓΥ f: T D Y YR.K, is tyrosine phosphorylated at 1 1 4 6 5 U 5 0 and 1 1 5 1 tyrosine relative to the catalytic domain of the _ island receptor. Put this whole body part (8 3 · 2 Fi u 1) with or without the test compound (6 β 2 5 litres) and 3 0 5 · 5 μl 8 1. 8 3 mmoles PES The reaction buffer, ρ Η 7.4, was precultured at 37 ° C for 10 minutes. The peptide substrate (10.5 liters, a final concentration of 50 micromolar) was adjusted to 37 ° C using a L A B L I N E Mu 1 t and B 10 k heater with a microplate connector. Pre-cultured microsomes (39.5 microliters) with or without test compounds were added to initiate the dephosphorylation reaction at 30 ° C for 30 minutes. The reaction was stopped by adding 200 liters of pores-ammonium molybdate-Tween20 terminator (MG / AM / Tw). This stopper contains 3 parts of 0.45% malachite green hydrochloride, 1 part of 4 β 2% ammonium molybdate tetrahydrate in 4 NHC 1 and (K 5% T wee η 2 0. Add 2 0 0 liters MG / AM / T w to the substrate and add 3 ί5 microliters of pre-cultured tadpole bodies with or without test compounds to obtain a control group. Color at room temperature for 5 hours, use a plate at 6 50 iim Counter (Μ ο 1 ecu 1 ar Devices) to measure absorbance. Prepare 4 samples and control duplicates. Measure 50 micromolar (final concentration) of the inhibitory effect of PTPase on chondrosomes. Calculation: Based on phosphate evaluation standards Curve, PTP enzyme activity can be released completely -68- This paper size applies Chinese National Standard (CNS) A4 specification (210 X 297 mm) ------------------- -Order --------- (Please read the notes on the back before filling in this page) 510900 A7 B7 V. Description of the invention U7) Molar phosphate / min / mg protein. Ρ Τ P __ of the test compound was prepared to calculate the percentage compared to the control ^ TC 50 of the test compound can be determined using the four-media nonlinear logistic regression of the PTPase activity of SAS 6 · 08, PR 0 CNLIN . All test compounds were administered at a concentration of 50 micromolar. The following results were obtained using the representative compounds of the present invention. Change in printed cases of employees' cooperatives from the Intellectual Property Bureau of the Ministry of Economic Affairs from the comparison% 9 -49.80 19 -30.40 20 2.13 21 -63.12 22 -28.57 23 -26.11 24 -65.31 29 -83.54 30 -60.32 31 -63.42 32 -89.41 33- 61.92 34 -63.01 35 -58.85 36 • 67.00 37 -49.83 38 -57.74 40 -83.88 41 -39.60 42 -63.41 43 -78.84 44 -68.50 45 -94.50 46 -91.00 _-47 -68.48 48 -44.69 49 -89.36 50- 81.27 52 -87.66 53 -81.83 Phenyl arsenic oxide (reference standard) -57.06.69 This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) (Please read the precautions on the back before filling this page ) tr --------- line _ ·) 109900A7 B7 V. Printed invention description printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs (W) & ji.ptpi Erji Fat

UtLU— (請先閱讀背面之注意事項再填寫本頁) 此檫準藥理試驗方法可評估重組鼠蛋白酪 (Ρ τ Ρ 1 Β )之抑制活性，其使用像使用相對於1 1 4 2 "" 1 1 5 3 胰島素受器激酶結構域之磷酪胺酸十二胜肱為受質’其於1 1 4 fi , 1 1 5 0及1 i 5 1酪胺酸磷化。所用方法及所得結果 P屬逑如下。將人重組P T P 1 B依G ο 1 d s t e i η (參見G ο 1 d s t e i η等人， Μ ο 1 · C e 1 1 β B i 〇 c h e ffi · 1 Ο 9，1 Ο 7 , 1 9 9 2 )方法製得。所用酶製劑係於小管含5 0 0 - 7 0 0微克/毫升蛋白質於3 3毫莫耳Tris-HCl，2毫莫耳EDTA，10%甘油及10毫眞耳硫氫乙醇。測量PTP酶活性：使用如Lanzetta等人。Anal· Bioehera· 1 0 0，9 5 , 1 9 7 9所逑孔雀綠-鉬酸銨方法，並使用平板計數器以測量由重組P T P 1 B釋放微毫莫耳之磷酸。試驗方法使用由A n a S p e c，I η c · ( S a n J 〇 s e，C A )合成之十二磷胜敝為受質。此胜肽，T R DI Y E T D Y Y R K ,相對於胰島素受器催化結構域，為酪胺酸磷化於1 1 4 6，1 1 5 0及1 1 5 1酪胺酸。將重組rPTPlB以緩衝液（ρΗ7·4，含33毫莫耳Tris-HC1 ，2毫莫耳ED ΤΑ及50毫莫耳2~硫氫乙醇）稀釋以得約1000 -20㈣徹毫莫耳/分/毫克蛋白質。將稀釋酶（8 3 .2 5毫升）於含或不含試驗化合物（6 · 25徹升）及3 0 5 · 5毫升之81 8 3 IBM HPES反應緩衝液，|>»?.4之下，於37<^預培養10分。將胜脉受質（10· 5毫升，終濃度51)毫莫耳）以具微平板連接本紙張尺度適用中國國家標準（CNS)A4規格（210 x 297公釐） 510900 A7 B7_ 五、發明說明（θ ) 器之L· A B I」I N E M u It i - B ]. 〇 k加熱器調至37°0。加入含或不含試驗化合物之預培養重組酶部份（39. 5毫升）以起始去磷化反於3 7 °C下3 G分。加入2 0 0毫升孔雀綠-鉬酸銨 - T w e e η 2 0中ih劑（M G / A M / T w )以中止反應。此中止劑含3 {分0 s 4 5 %孔雀線_酸鹽，1份4 . 2 %鉅酸銨四水合物於4 Ν HC]及0.5% Tween20。加入2 0 0毫升MG/AM/Tw至受質並加入3 9 . 5毫升含或不含試驗化合物之預培養重組酶部份可得對照組。於室温下呈色〇 . 5小時，於6 5 Q η in下使用平板計數器（Μ ο 1 e c u 1 a r I) e v i c e s )測量趿光度。準備4個樣本及對照重覆。計算：基於磷酸鉀標準曲線，P T P酶活性可以釋放微毫莫耳磷酸鹽/分/毫克蛋白質表示^試驗化合物之重組 P T P 1 B抑制作用以相較於磷酸酶對照之百分比而計算。使用由S A S 6。0 8販，P R 〇 C N L I N，之P T P酶活性之四介質非線性對數迴歸可測定試驗化合物之I C 5〇。結果如下。 --------------------訂--------- (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 -7 1- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 B7 五、發明說明（7。）經濟部智慧財產局員工消費合作社印製例 IC50 (μΜ) 9 0.539 19 0.697 21 0.381 23 0^43 29 0.115 30 0.869 31 0.049 32 0.060 33 0.029 34 0.100 35 0.273 36 1.34 ' 37 052 38 0.299 39 1.74 40 0.110 41 0.729 42 0.089 43 0.171 44 0.237 45 0.203 46 1.19 47 0.095 48 0.083 49 0.384 50 0.457 51 2.21 52 0.287 53 0.204 54 0.982 55 0.059 56 0.489 57 1.90 59 2.20 60 1.51 -72 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） -------------------^--------- (請先閱讀背面之注意事項再填寫本頁) 510900 A7 B7 五、發明說明（力） —例 IC50 (μΜ) 61 0.164 62 0.028 63 0.138 64 〇J9 65 Οδ 68 0.080 70 0.33 71 1.19 72 0.48 76 0.45 78 0.27 79 0.78 83 0.13 88 0.32 苯基氧化砷 39.7 (參考標準）正釩酸鈉 244.8 (參考標進）鉬酸銨四水合物 8.7 (參考標進） (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印制衣本發明代表化合物之降低血葡萄糖能力係由活體内標準藥理試驗法，使用鼠（〇 b / 〇 b )而闡明。所用方法及所得結果圈述如下。非胰島素相關（N I D D Μ )病特徵為肥胖，高血糖，異常胰島素分泌，高胰島素及抗胰島素性。遣傳肥胖-高血糖ob/ob鼠具許多此類代謝異常，且可用以研發治療 N i D D Μ 之低血糖劑之模型（C ο 1 e m a η，D e : D i a b e t ο 1 〇 g i a 1 4 : 1 4 1 ~ 1 4 8 ? 1 9 7 8 )。各試驗中，將年齡相似鼠（雄或雌〇b/〇b(C57 B1/6J) 及其痩塑（〇 b / + 或 + / +，J a c k s ο n L a b · ) ，2 〜5 肱（1 0 〜 0 5克）），依體重隨機分為4群10隻鼠。將鼠每5隻養於1 個欄中，餵以一般飼料及水。由管飼法（懸浮於〇 · 5毫升之（K 5 %甲基纖維素）瀋於飲水；或混與食物之方法每一？ 3 - 裝--------訂---------^^^1. 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 B7 五、發明說明（7>) 予體給Fr 天公由 I 劑物合化 0 物合化驗試以算一一 1'lrr 重體以0 週每依量劑 ο 天 /域克區毫生 ο1# 20活一以 5 a 表予投UtLU— (Please read the precautions on the back before filling out this page) This quasi-pharmacological test method can evaluate the inhibitory activity of recombinant mouse protein casein (P τ Ρ 1 Β), and its use is like using relative to 1 1 4 2 " " 1 1 5 3 Insulin receptor kinase domain phosphotyrosine twelve tribrachias is a substrate, which is phosphorylated at 1 1 4 fi, 1 1 50 and 1 i 5 1 tyrosine. The method used and the results obtained are as follows. Recombinant human PTP 1 B according to G ο 1 dstei η (see G ο 1 dstei η et al., Μ ο 1 · C e 1 1 β B i 〇che ffi · 1 0 9, 1 0 7, 1 9 9 2) Method. The enzyme preparation used was a tube containing 500-700 micrograms per milliliter of protein in 33 millimoles of Tris-HCl, 2 millimoles of EDTA, 10% glycerol, and 10 millimoles of thiohydrin ethanol. Measurement of PTPase activity: Uses such as Lanzetta et al. The Anal Bioehera 1 0 0, 9 5, 1 9 7 9 method of malachite green-ammonium molybdate was used, and a plate counter was used to measure the release of micromolar phosphoric acid from recombinant P T P 1 B. Test method Twelve phosphorus tritium, synthesized from Ana Spec, I η c · (San J ose, CA), was used as the substrate. This peptide, T R DI Y E T D Y Y R K, relative to the catalytic domain of the insulin receptor, is tyrosine phosphorylated at 1 1 4 6, 1 15 0 and 1 15 1 tyrosine. Recombinant rPTPlB was diluted with a buffer solution (ρΗ7.4, containing 33 millimoles of Tris-HC1, 2 millimoles of ED TA, and 50 millimoles of 2 to thiohydrin ethanol) to obtain about 1000-20 millimoles / minute / Mg of protein. Dilute the enzyme (8.3.25 ml) with or without the test compound (6.25 liters) and 3.05 · 5 ml of 81 8 3 IBM HPES reaction buffer, | > »?. 4 of Next, pre-cultivate at 37 < ^ for 10 minutes. The Shengmai substrate (10 · 5ml, final concentration: 51) millimolar) is connected with a micro-tablet. The paper size applies the Chinese National Standard (CNS) A4 specification (210 x 297 mm) 510900 A7 B7_ V. Description of the invention (Θ) L · ABI of the device "INEM u It i-B]. 〇k heater was adjusted to 37 ° 0. A precultured recombinase portion (39.5 ml) with or without the test compound was added to initiate dephosphorylation inverse to 3 G at 37 ° C. Add 200 ml of malachite green-ammonium molybdate-Tw e e η 2 0 to the ih agent (MG / AM / TW) to stop the reaction. This terminator contains 3 {minutes of 0 45% of peacock thread salt, 1 part of 4.2% ammonium giant acid tetrahydrate in 4N HC] and 0.5% Tween20. A control group was obtained by adding 200 ml of MG / AM / Tw to the substrate and adding 39.5 ml of the pre-cultured recombinase portion with or without the test compound. The color was developed at room temperature for 0.5 hours, and the luminosity was measured at 65 Q η in using a plate counter (M o 1 e c u 1 a r I) e v i c e s). Prepare 4 samples and duplicates. Calculation: Based on the potassium phosphate standard curve, the P T P enzyme activity can release micromolar phosphate / min / mg protein to indicate that the inhibitory effect of the recombinant P T P 1 B test compound is calculated as a percentage compared to the phosphatase control. The I C 50 of the test compound can be determined using a non-linear logarithmic regression of four mediators of P T P enzymatic activity sold by S A S 6.0, P R O C N L I N. The results are as follows. -------------------- Order --------- (Please read the notes on the back before filling out this page) Staff Consumption of Intellectual Property Bureau, Ministry of Economic Affairs Printed by a cooperative -7 1- This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 510900 A7 B7 V. Description of the invention (7.) IC50, printed by the Intellectual Property Bureau of the Ministry of Economic Affairs, consumer consumption μM) 9 0.539 19 0.697 21 0.381 23 0 ^ 43 29 0.115 30 0.869 31 0.049 32 0.060 33 0.029 34 0.100 35 0.273 36 1.34 '37 052 38 0.299 39 1.74 40 0.110 41 0.729 42 0.089 43 0.171 44 0.237 45 0.203 46 1.19 47 0.095 48 0.083 49 0.384 50 0.457 51 2.21 52 0.287 53 0.204 54 0.982 55 0.059 56 0.489 57 1.90 59 2.20 60 1.51 -72 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ---- --------------- ^ --------- (Please read the precautions on the back before filling out this page) 510900 A7 B7 V. Description of the invention (force) — Example IC50 (μΜ) 61 0.164 62 0.028 63 0.138 64 〇J9 65 〇δ 68 0.080 70 0.33 71 1.19 72 0.48 76 0.45 78 0.27 79 0. 78 83 0.13 88 0.32 Phenylarsenic oxide 39.7 (reference standard) Sodium orthovanadate 244.8 (reference standard) Ammonium molybdate tetrahydrate 8.7 (reference standard) (Please read the precautions on the back before filling this page) Economy Printed by the Consumer Cooperative of the Ministry of Intellectual Property Bureau. The ability to reduce blood glucose of the representative compound of the present invention is illustrated by standard pharmacological test methods in vivo using mice (0b / 0b). The methods used and the results obtained are outlined below. Non-insulin-associated (NIDDM) disease is characterized by obesity, hyperglycemia, abnormal insulin secretion, hyperinsulinism, and insulin resistance. Send obesity-hyperglycemic ob / ob mice have many of these metabolic abnormalities and can be used to develop models for the treatment of hypoglycemic agents in N i DD Μ (C ο 1 ema η, De: D iabet ο 1 〇gia 1 4 : 1 4 1 ~ 1 4 8? 1 9 7 8). In each experiment, mice of similar age (male or female 0b / 〇b (C57 B1 / 6J) and their shape (0b / + or + / +, Jacks ο n L ab ·), 2 to 5 brachial (1 0 ~ 0 5 g)), randomly divided into 4 groups of 10 mice according to body weight. The rats were housed in a pen every 5 rats, and were fed with general feed and water. By tube feeding method (suspended in 0.5 ml of (K 5% methyl cellulose) sink in drinking water; or mixed with food each? 3-Packing -------- Order ---- ----- ^^^ 1. This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 510900 A7 B7 5. Description of the invention (7 >) The chemical compound test is used to calculate the weight of the 1'lrr weight body at 0 weeks per dose ο day / domain grams area shengsheng ο1 # 20 live one to 5 a table for investment

A 經濟部智慧財產局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) Θ 8 Ci ο 0 a z h a c t J 1 見 s 參 i c 50 照二對 4 正 2 天-/?基重苄疆 } 基氧甲克基毫己璟 o o 11 斤公甲A Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) Θ 8 Ci ο 0 azhact J 1 See s ic 50 Photo two pairs 4 positive 2 days-/? Basis weight benzyl }} Oxymethoxamine

B S Θ θ β s b ya w .1 D t s i Γ h c η ο S r θ t θ p 2 3 8 3 8 I o oo 8 a 糖 D1萄及« T漿，血低降著顯可其或脈靜尾由 C 晨體早載天 / 4 T1 給或僅7 f4 照第對於血滴二集收後頭升於徹 C 用 5 者使約予， {投漿BS Θ θ β sb ya w .1 D tsi Γ hc η ο S r θ t θ p 2 3 8 3 8 I o oo 8 a The early morning days of C / 4 T1 or only 7 f4 according to the second set of blood drops after the first head rises to C, make the appointment with 5, {

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a η A 法血飼離管分由心日離每〇物血合集化收當時rs 度濃糖萄0 量測相以比分由百〇化算變計糖值萄糖 0 萄漿« 血漿之血天均 4 * 1¥ 或之 7 I ff 4,_ 第載於予鼠給各僅將於對a η A blood feeding off-tube points from the heart to the blood of each 〇 blood collection at the time rs degrees concentrated sugar 0 measurement phase to the score from 100 calculations to change the sugar value grape 0 grape «blood of plasma The average day 4 * 1 ¥ or 7 I ff 4, _ is contained in Yushu to each only

t t θ η u D 以理驗處試別較個比與氏倩單痦 f 反 ϋι» 萄 8 ί 匍.1 漿5 血照對計化估變可著析顯分之方鼠變物之合 )b 1 /1 S A S S Μ c 降可其因劑糖血高抗為物合化明〇發景本糖示血顯之果鼠結病表尿下糖低 4 7 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）tt θ η u D Compare the test with rational test and compare it with Shi Qiandan 痦 fϋϋ »Grape 8 ί 匍. 1 5 5 Blood photos can be used to analyze the changes of the rat's variants. ) b 1/1 SASS mc c can be reduced due to the high blood sugar resistance of the agent is the combination of chemical compounds. 0 The scene shows that the sugar shows blood in the fruit rat's disease and the low sugar in the urine. 4 7 This paper size applies Chinese national standards ( CNS) A4 size (210 X 297 mm)

—I _1 §_1 ·ϋ ϋ ·ϋ ^ ^ tmf n ϋ ·ϋ ϋ an I 510900 A7 B7 五、發明說明（〇 ) 例劑量（mg/Kg) 從載體之葡萄糖變化％從載體之胰島素變化％ 29 100 -48.63 -89.59 29 25 -38.18 -80.50 29 10 -18.6 (a) -48.11 32 25 -15.68 (a) -48.35 33 25 -21.10(a) -39.3 35 25 -25.58 -2.98 (a) 40 100 -28.20 -90.80 42 25 -32.5 b 43 25 -45.2 b 44 25 -17.2 b 48 25 -20.1 b 49 10 -35.1 b 61 10 -32.8 (c) b Ciglitazone (參考檫準） 100 -43 -39 (請先閱讀背面之注意事項再填寫本頁) a -在此_量無顯箸活性（p < 0 · 0 5 ) h -未測 c -在0小時測定經濟部智慧財產局員工消費合作社印製基於標準藥理試驗法所得結果，本發明化合物顯示可於患耱尿病之鼠中抑制P T P酶活性及降低血《萄糖之量，因而可用以治療與抗胰島素症及高血糖症相關之代謝異常。特言之，本發明化合物可用以治療或抑制I I型糖尿病，及如I型糖尿病異常中調控葡萄糖之量。此處調控一詞意指維持《萄糖之量於一般臨床範圍。投予此化合物！之有效劑量可以約1毫克/公斤〜2 5 0毫克/公斤之單日劑量紿予，且可以單一劑量或2份以上次分劑景投予。投予此劑量可由可引導活化合物至患者血液之方法，含口投予，由植入，非腸胃投予（含靜脈， -7 5- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印製 510900 A7 B7 五、發明說明（Μ ) 腹腔及皮下注射），肛門，***及皮膚投予。依本刊載目的，經皮膚投予含所有由身體表面穿越如表皮及粘膜組織之身體内膜者此投予可將本發明化合物或其製藥容許鹽以洗液，乳液，泡沫，貼布，懸浮液，溶液，及栓_ (肛門及***）投予。本發明活性化合物之口投予處方可含任何習用口投予形式，含錠劑，膠囊，鼻吸入形式，小丸，變錠及口投予液體，懸浮液或溶液。_囊可含活性化合物混以惰性濾器及/或稀釋_如製藥容許澱粉（如玉米，馬鈐薯或木馨），糖，合成增甜劑，粉狀纖維素，如結晶纖維素及徹晶纖維素，粉，明膠，膠等。適當錠劑處方可依習用壓縮，溼製粒或乾製粒方式，使用製藥容許稀釋劑，結合劑，潤滑劑，崩散劑，懸浮液或穩定劑，含如下但不限於此，如硬脂酸鎂，硬脂酸，十二硫酸鈉，微晶纖維素，羧甲基纖維素鈉，聚乙烯吡咯啶，明_，藻酸， ***_，黃顧，檸檬酸鈉，矽酸鹽複合物，碳酸鈣，甘胺酸9糊精，蔗糖，山梨糖醇，磷酸二鈣，硫酸鈣，乳糖，高嶺土，甘露糖醇，氯化鈉，滑石，乾澱粉及糖粉。此處口投予可使用標準遲緩或時放處方以變化活性化合物之吸收。栓劑處方可由習用物質，含可可奶油，含或不含蠛（以改變栓劑之熔點），及甘油。亦可使用水溶性栓_基質，如各種分子量之聚乙烯乙二醇。需知本發明化合物劑量，形式及投予方法可依疾病及待治療病人，及依醫生指示而定。宜投予小劑量之一以 -7 6- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂--------- (請先閱讀背面之注意事項再填寫本頁) 510900 A7 _B7_ 五、發明說明（坏）上化合物並増加劑量直達欲得結果。下列製法詳逑製備本發明代表化合物之方法。 (請先閱讀背面之注意事項再填寫本頁) 例1 2 . 3 -二甲瞟盼將3 -甲基瞎吩羧醛（2 0克，0 . 1 5 9莫耳），阱水合物 (3 1毫升）及乙二醇（7 2毫升）加熱回流2 0分。冷郤至低於]0 G °C後，加入氫氧化鉀（2 2 . 9克，0 . 4 0 8莫耳）—I _1 §_1 · ϋ ϋ · ϋ ^ ^ tmf n ϋ · ϋ ϋ an I 510900 A7 B7 V. Description of the invention (0) Example dosage (mg / Kg)% change from glucose in the carrier% change from insulin in the carrier% 29 100 -48.63 -89.59 29 25 -38.18 -80.50 29 10 -18.6 (a) -48.11 32 25 -15.68 (a) -48.35 33 25 -21.10 (a) -39.3 35 25 -25.58 -2.98 (a) 40 100- 28.20 -90.80 42 25 -32.5 b 43 25 -45.2 b 44 25 -17.2 b 48 25 -20.1 b 49 10 -35.1 b 61 10 -32.8 (c) b Ciglitazone (reference standard) 100 -43 -39 (please first Read the notes on the back and fill in this page) a-No significant activity in this amount (p < 0 · 0 5) h-not measured c-measured at 0 hours As a result of standard pharmacological tests, the compounds of the present invention have been shown to inhibit PTPase activity and reduce blood glucose levels in rats suffering from diarrhea, so they can be used to treat metabolic abnormalities associated with insulin resistance and hyperglycemia. In particular, the compounds of the present invention can be used to treat or inhibit type I diabetes, and to regulate the amount of glucose such as in type I diabetes abnormalities. The term regulation here means maintaining the amount of glucose in the general clinical range. Administer this compound! The effective dose can be administered in a single daily dose of about 1 mg / kg to 250 mg / kg, and can be administered in a single dose or in two or more divided doses. This dose can be administered by a method that can guide the living compound to the patient's blood, including oral administration, implantation, parenteral administration (including intravenous, -7 5-This paper size applies to Chinese National Standard (CNS) A4 specifications (210 X 297 mm) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7 V. Description of the Invention (M) Intraperitoneal and subcutaneous injection), anal, vaginal and skin administration. For the purpose of this publication, transdermal administration to all body inner membranes that pass through the surface of the body such as the epidermis and mucosal tissues. This administration can apply the compounds of this invention or their pharmaceutically acceptable salts to lotions, emulsions, foams, patches, suspensions Liquid, solution, and suppository (anal and vaginal) administration. The orally administered formulations of the active compounds of the present invention may contain any conventional oral administration form, including lozenges, capsules, nasal inhalation forms, pellets, tablets, and oral administration liquids, suspensions or solutions. _ Capsules can contain active compounds mixed with inert filters and / or diluted_ such as pharmaceuticals allow starch (such as corn, yam or cassava), sugar, synthetic sweeteners, powdered cellulose, such as crystalline cellulose and cut crystals Cellulose, powder, gelatin, gum, etc. The appropriate tablet formulation can be compressed, wet granulated or dry granulated according to customary methods. Pharmaceutically acceptable diluents, binders, lubricants, disintegrating agents, suspensions or stabilizers are used, including but not limited to, such as stearic acid. Magnesium, stearic acid, sodium lauryl sulfate, microcrystalline cellulose, sodium carboxymethylcellulose, polyvinylpyrrolidine, amine, alginic acid, arabinol, Huang Gu, sodium citrate, silicate complex, Calcium carbonate, glycine 9 dextrin, sucrose, sorbitol, dicalcium phosphate, calcium sulfate, lactose, kaolin, mannitol, sodium chloride, talc, dry starch and powdered sugar. Oral administration here may use standard retardation or time-of-day prescriptions to alter the absorption of the active compound. Suppositories can be formulated with conventional substances, with or without cocoa butter, with or without tincture (to change the suppository's melting point), and glycerin. It is also possible to use water-soluble suppositories, such as polyethylene glycol of various molecular weights. It is to be understood that the dosage, form and administration method of the compound of the present invention may depend on the disease and the patient to be treated, and on the instructions of the doctor. It is advisable to administer one of the small doses to 7 6- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ------------------- -Order --------- (Please read the notes on the back before filling in this page) 510900 A7 _B7_ V. Description of the Invention (Bad) Add the compound and increase the dosage until you get the desired result. The following production method details the method for preparing the representative compound of the present invention. (Please read the precautions on the reverse side before filling out this page) Example 1 2. 3-Dimethylpyridine 3-methylbenzophene carboxaldehyde (20 g, 0.1 59 mol), trap hydrate ( 31 ml) and ethylene glycol (72 ml) were heated under reflux for 20 minutes. After cooling to less than 0 G ° C, potassium hydroxide (22.9 grams, 0.48 mol) was added

，加熱至1 2 5 - 1 3 Q °C 1 . 5小時。冷卻至室溫後加至水。將水溶液以***萃取，將***層以5%HC1及食鹽水洗。乾燥（硫酸移除溶劑，將油以驟層析（戊烷為溶離劑）可得標題化合物之油（1 5 · 8 1克，8 9 Γ) : N M R (CDC13); δ 6.97 (d，1Η，J = 8 Ηζ)，6.77 (d，1Η，J = 8 Ηζ)，2·35 (s，3Η)，2.14 (s， 3H). 例2 4 , 5 -二甲瞟Ρ分- 2 -某-（茉某）-甲醇將正丁鋰（1 9。6毫升，4 9 . 1毫莫耳，2 , 5 N於己烷），於_ 7 8 °C及乾氮氣下滴加2 , 3 -二甲瞎吩（5 . 0克，經濟部智慧財產局員工消費合作社印製 44 J毫莫耳）之THF ( 100毫升）攪拌溶液。回溫至 0 °C 3 0分後再冷卻至-7 8 °C。加入苯醛（5 . 0毫升，4 9 . 1 毫莫耳）。4 5分後5加入飽和氯化氨溶液s於水及乙醚中分層。將***層以食鹽水洗後濃縮。將所得油碾製以乙_可得標題化合物之白色固體（7 . 7 7克，8 0 % ), And heated to 1 2 5-1 3 Q ° C for 1.5 hours. Add to water after cooling to room temperature. The aqueous solution was extracted with ether, and the ether layer was washed with 5% HC1 and brine. Drying (removing the solvent with sulfuric acid, and subjecting the oil to flash chromatography (pentane as eluent) gave the title compound as an oil (15.81 g, 8 9 Γ): NMR (CDC13); δ 6.97 (d, 1Η , J = 8 Ηζ), 6.77 (d, 1Η, J = 8 Ηζ), 2.35 (s, 3Η), 2.14 (s, 3H). Example 2 4, 5 -dimethylformate points-2- -(Jomo) -methanol Lithium n-butyllithium (19.6 ml, 49.1 mmol, 2, 5 N in hexane) was added dropwise at -8 ° C and dry nitrogen at 2, 3 -Stirred solution of dimethylphene (5.0 g, 44 J millimoles printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs) in THF (100 ml). Return to 0 ° C for 30 minutes and then cool to- 7 8 ° C. Add benzoaldehyde (5.0 ml, 49.1 mmol). After 4 5 minutes, add saturated ammonium chloride solution and separate in water and ether. Wash the ether layer with brine. Concentrated. The obtained oil was milled with ethyl acetate to give the title compound as a white solid (7.7 g, 80%)

:熔點 8 0 - 8 1 °C : N M R ( C D C 1 3 ) ; 5 7 . 4 5 ( d d d 5 J -77- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 B7 五、發明說明（ (請先閱讀背面之注音？事項再填寫本頁) =8, 1, 1 Hz，2H), 7·37 (ddd, J = 8, 8, 1 Ηζ, 2Π), 7·3 (ηι, 1H), 6.57 (s, 1H), 6.93 (s, 1H, OH), 2.29 (s, 3H), 2.05 (s, 3H); MS (El) (M+) 218 (45%, MI): Anal Calc-for C13H140S: C, 71.52, H, 6.46, N, 0.00. Found: C, 71.41, H, 6.42, N, 0.09. 例3 2 -亨某-4 . Γ)-二申盼將三氟乙酸（5 0毫升）於6 0分内滴加至含4， 5 -二甲瞎吩-2 -基-(苯基）-甲醇（7 · 7克，3 5 · 3毫莫耳），S朋氳化鈉（6 · 6 7克，1 7 7毫莫耳）及***（6 0 0毫升）之〇 °C攪拌溶液。1 · 5小時後，加至1 (Π N a 0 Η ( 6 0 0毫升）並攪拌Q · 5小時。分層將***層以1 0 % N a 0 Η，食鹽水洗並乾燥（硫酸鎂）。濃縮***層可得標題化合物之油（6 . 7 3 克，9 U ) : NMR (CDC13); δ 7.33-7.19 (m, 5H), 6.47 (s, 1H), 4.03 (s, 2H), 2.27 (2, 3H)，2.06 (s，2H); MS (El) (M+) 202 (45%，MI)· 例4 (2 -节某- 4 · 5 -二甲嗦盼- 3 -某）-(4 -田氨茱甚）-申議將四氯化錫（4 6毫升，71 · 7 6毫莫耳），於1 〇分内，經濟部智慧財產局員工消費合作社印製 -7 8 °C及乾氮氣下滴加至含2 -苄基-4，5 -二甲11塞吩（6 · 6 克，3 2 · 6 2毫莫耳），對甲氧苯甲醯氯（5 · 9 0克，3 4 · 6 毫莫耳）及二氯甲烷ί 1 2 0毫升）之攪拌溶液。於-7 8 °C 下5小時後，於2小時内緩慢回溫至室溫。加至水中並以***萃取。將***層以飽和重硕酸鈉溶液及食鹽水洗〇移除溶劑，將油碾製以***可得標題化合物之摻白色固體ί 9 · 6 2克，8 8 % ):熔點8 5 ~ 8 6 °C : -78- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印製 510900 A7 B7___ 五、發明說明（V ) NMR (CDC13); δ 7.80 (ddd, J = 8, 8, 1 Hz, 2H), 7.24-7.10 (m, 5H), 7.92 (ddd, J = 8, 8, 1 Hz, 2H), 3.93 (s, 2H), 3.88 (s，3H)，2·28 (s，3H), 1.90 (s，3H); MS (El): 336 (100%, MI); Anal. Gale, for C21H20O2S: C, 74.97, H, 5.99, N, 0.00. Found: C, 75.11, H, 6.02, N, 0.05. 满5 4-(2. 3-二串棻駢「2a 3-bU富盼- 4二基）-B酚將三溴化硼（20毫升，212毫莫耳）於-78°C及乾氮氣下滴加至含（2〜苄基-4， 5_二甲S室吩-3-基）~ (4 -甲氣苯基） -甲酮（9,40, 27J毫莫耳）之二氯甲烷（95毫升）之攪拌溶液。回溫至室溫後攪拌4小時。冷卻至0°C，中心加入水以中止反瞧，移除溶劑。加入更多水，濾集沈澱，水洗並以***碾製可得標題化合物之淡紫色固體（8. 23克，97%) :熔點 1 6 5 - 1 G 8 °C : NMR (DMSO-d6); δ 9.62 (s, 1H), 8.43 (s, 1H), 7.94 (d, J = 8 Hz, 1H), 7.43 (m, 2k), 7.32 (ddd, J = 8 1 1 Hz 1H) 7 11 (d^ = 8 Hz, 2H), 6.90 (d, J = 9 Hz, 2H), 2.39 (s, 3H), 1.61 (； 3H); MS (Eli： 304 (100%, MI).: Melting point 8 0-8 1 ° C: NMR (CDC 1 3); 5 7. 4 5 (ddd 5 J -77- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 510900 A7 B7 V. Explanation of the invention ((Please read the note on the back? Matters before filling out this page) = 8, 1, 1 Hz, 2H), 7.37 (ddd, J = 8, 8, 1 Ηζ, 2Π), 7 3 (ηι, 1H), 6.57 (s, 1H), 6.93 (s, 1H, OH), 2.29 (s, 3H), 2.05 (s, 3H); MS (El) (M +) 218 (45%, MI): Anal Calc-for C13H140S: C, 71.52, H, 6.46, N, 0.00. Found: C, 71.41, H, 6.42, N, 0.09. Example 3 2-Hengmou-4. Γ) -Secondspan Trifluoroacetic acid (50 ml) was added dropwise over 60 minutes to a solution containing 4,5-dimethylbenzophen-2-yl- (phenyl) -methanol (7.7 g, 35.3 mmol). ), Sodium pentoxide (6.67 g, 177 mmol) and ether (600 ml) were stirred at 0 ° C. After 1 · 5 hours, add to 1 (Π N a 0 Η (600 ml) and stir for Q · 5 hours. Separate the ether layer with 10% N a 0 Η, wash with brine and dry (magnesium sulfate) Concentrate the ether layer to obtain the title compound as an oil (6.73 g, 9 U): NMR (CDC13); δ 7.33-7.19 (m, 5H), 6.47 (s, 1H), 4.03 (s, 2H), 2.27 (2, 3H), 2.06 (s, 2H); MS (El) (M +) 202 (45%, MI) · Example 4 (2-knots-4 · 5-dimethypan-3-certain) -(4 -Tian Jiang Zhu Ju)-It is proposed that tin tetrachloride (46 ml, 71.76 millimoles) will be printed within 10 minutes by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. 7 8 ° C and dry nitrogen to a solution containing 2-benzyl-4,5 -dimethyl 11 phene (6.6 g, 3 2 · 6 2 mmol), p-methoxybenzidine chloride (5 · 90 g, 3 4 · 6 mmol) and a stirred solution of dichloromethane (120 ml). After 5 hours at -7 ° C, slowly warm to room temperature within 2 hours. Add to water and extract with ether. The ether layer was washed with a saturated sodium bisulfate solution and brine. The solvent was removed, and the oil was triturated with ether to obtain the title compound as a white solid (9 · 62 g, 88%). Melting point 8 5 ~ 8 6 ° C: -78- This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7___ V. Description of Invention (V) NMR (CDC13); δ 7.80 (ddd, J = 8, 8, 1 Hz, 2H), 7.24-7.10 (m, 5H), 7.92 (ddd, J = 8, 8, 1 Hz, 2H), 3.93 (s, 2H), 3.88 (s, 3H), 2.28 (s, 3H), 1.90 (s, 3H); MS (El): 336 (100%, MI); Anal. Gale, for C21H20O2S: C, 74.97, H, 5.99, N, 0.00. Found: C, 75.11, H, 6.02, N, 0.05. Full 5 4- (2. 3-Two-string 棻骈 "2a 3-bU Fupan-4 diyl) -B phenol will tribromize Boron (20 ml, 212 mmol) was added dropwise at -78 ° C under dry nitrogen to a solution containing (2 ~ benzyl-4, 5_dimethyl S compartment phen-3-yl) ~ (4-methylbenzene Base)-a stirred solution of methyl ketone (9,40, 27J millimoles) in dichloromethane (95 ml). Warm to room temperature and stir for 4 hours. Cool to 0 ° C, add water to the center to stop the reaction. , Remove the solvent. Add more water, filter the precipitate, wash with water and triturate with ether to obtain the title compound as a lilac solid (8. 23 g, 97%): melting point 16-5-1 G 8 ° C: NMR (DMSO -d6); δ 9.62 (s, 1H), 8.43 (s, 1H), 7.94 (d, J = 8 Hz, 1H), 7.43 (m, 2k), 7.32 (ddd, J = 8 1 1 Hz 1H) 7 11 (d ^ = 8 Hz, 2H), 6.90 (d, J = 9 Hz, 2H), 2.39 (s, 3H), 1.61 (; 3H); MS (Eli: 304 (100%, MI).

例R 乙酸4 -（ 2 . 3 -二闲着駢f 2 . 3 - b 1 -瞎盼j-甚·）-荣酯將乙酐（0.68毫升，7.20毫莫耳）加至含4_(2，3-二甲養駢[2 , 3 - b〗-瞎粉-4 -基> ~觸（2 · 〇克，g · 5 7毫莫耳）之嗽晚（8 · (5毫升）攪拌冰水溶液。1 7小時後加至濾集沈澱，以5%HC1，水洗，並以***碾製。真空乾燥可得標題化合物之白色固體（1· 99克，88%): 第點 1 4 ? - 1 5 0 °C : NMR (DMSO-d6); δ 8·49 (s，1H)，7.94 (d，J = 8 Hz， - 79- 本紙張尺度適用中國國家標準（CNS)A4規格（210 χ 297公釐) " 一~ --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 510900 Α7 Β7 五、發明說明（7〇 (請先閱讀背面之注意事項再填寫本頁) 1H), 7.46 (ddd, J = 8, 6, 2, 1H), 7.38 (ddd, J = 8, 1, 1 Hz, 1H), 7.39-7.34 (m, 2H), 7.28 (d, J = 8 Hz, 2H), 6.90 (d, J = 9 Hz, 2H), 2.40 (d, J = 1 Hz, 3H), 2.34 (s, 3H), 1.57 (d, J = 1 Hz, 3H); MS (El): 346 (90%, MI), 304 (100%); Anal. Calc, for C22H1802S: C, 76.27, H, 5.34, N. 0.00. Found: C, 75.88, H. 5.04, N, 0.28. 例？ m a- ( - 2. 3-:二牢審駢「2 * 3-hi -m m -4-¾ )_ :―審Jl— 將溴（η e 3 2 fi毫升，6 ·】5毫莫耳）之二氯甲烷（9毫升於1 5分内及黑暗下，於-7 8 °C及乾氮氣下滴加至乙酸4 - ί 2， 3 _二甲萘駢[2，3 - b ]-瞎吩-4 -基）-苯酯 (1 · 8 7克，5 j 1毫莫耳）及氯化鐵（I I I) ( 5 Ο毫克， 0β 31毫莫耳）之二氯甲烷（47毫升）。10分後，加入稀釋亞硫酸氫銷溶液，於水及***中分層。將***層以食鹽水洗並濃縮可得標題化合物之白色固體（2 . 0 9克 ,91% ):熔點 1 9 0 - 1 9 1 : NMR (DMSO-d6); 8.20 (d， J = 8 Hz, 1H), 7.65 (ddd, J = 8, 7, 1, 1H), 7.49 (ddd, J = 8, 7, 1 Hz, 1H), 7.43-7.38 (m, 1H), 7.40 (d, J = 9 Hz, 2H), 7.30 (d, J = 9 Hz, 2H), 2.43 (d, J = 1 Hz, 3H), 2.33 (s, 3H)，1·55 (d，J = 1 Hz, 3H); MS (El): 1 溴同位素式樣；424 (95%, MI), 426 (100%); Anal. Calc, for C22H17Br02S: C, 62.12, H, 4.03, N, 0.00. Found: C, 62.46, H, 4.05, N, 0Ό9. 例8 經濟部智慧財產局員工消費合作社印製 4 -（ 9 -湟-2 · 3 - ：ι： φ ^ SI Γ 2 . 3 - b 1 - g:拿 P分- 4 -甚）-附將氫氧化鉀溶液（6·0毫升，6.G毫莫耳）加至於室溫下攪拌之乙酸4 - ( 9 -溴-2 , 3 -二甲萘駢[2， 3 - b ]-瞎盼 - 4-基）-苯酯（0·48克，1·14毫莫耳）在THFC15毫升） /甲醇（丨0毫升）。1小時後，移除有機溶劑，加入水， ~80~ 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 經濟部智慧財產局員工消費合作社印製 A7 B7 五、發明說明（79 ) 以1 0 % H C 1酸化，將所得固體以水洗並以乙醱碾製，真空乾燥可得標題化合物之白色固體（0.32克，73%) :熔點 165-: NMR(DMSO-d6);S9.68 (s，1Η)，8.17 (d, J = 8 Hz, 1H), 7.62 (ddd, J = 8, 6, 1 Hz； 1H), 7.50 (d, J = 8 Hz, 1H), 7.44 (ddd, J = 8, 7, 1 Hz, 1H), 7.13 (d, J = 9 Hz, 2H), 6.91 (d, J = 9 Hz, 2H), 2.42 (d, J = 1 Hz，3H), 1.59 (d, J = 1 Hz，3H); MS (El): 1 溴同位素式樣 382 (95%，MI)， 384 (100%); Anal. Calc, for C20H15BrOS: C, 62.67, H, 3.95, N, 0.00. Found: C, 62.40, H, 3.91, N, 0.09. 例9 ?· · 6 -二溴-4 二(9 -瘪-2 * 3 -二串縈 1¾「2 · 3 - h Ί -瞎盼- 4 - 某）-g# 將溴（（K34毫升，5·?4毫莫耳）之乙酸（5毫升），加至於室溫下攪拌4- ( 9-溴-2，3-二甲綦駢[2，3-b】-瞎吩-4-基酚（1.10克，2.87毫莫耳乙酸鉀（2.82克 ,28. 7莫耳）及乙酸（31毫升）溶液。K 5小時後，加入水（2GQ毫升）及少量硫鈉固體。過濾，將固體以水洗，以乙隱碾製，真空乾燥可得標題化合物之白色固體 (1 β 5 2 克，8 8 % ):熔點 172-174°C: NMR (DMSOd6); 11.95 (broad s，1Η), 10.20 (broad s, 1H), 8.19 (ddd, J = 8,1,1 Hz, 1H), 7.65 (ddd, J = 8, 6, 1 Hz, 1H), 7.59(s, 2H), 7.51-7.49 (m, 2H), 2.44 (d, J = 1 Hz, 3H), 1.90 (s, 3H), 1.64 (d, J = 1 Hz，3H);MS(+FAB):3 溴同位素式樣 538 (40%)，540 (100%), 542 (90%)， 544 (50%); Anal. Calc, for C22H13Br30S C2H402: C, 43.95, H, 2.85, N, 0.00. Found: C, 44.13, H, 2.66, N, 0.12. 例]0 g—馨一Jl—二A二—j一Lt·—S二—IL··里―董—MJ12_, 3 _b Ί ~ 瞟盼- 4 _ 基）_-¾ 酯於含4 - ( 2，3 -二甲萘駢[2 , 3 - b卜時粉-4 -基）© >81- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） ----— II----------丨丨訂·--------^^^1 (請先閱讀背面之注意事項再填寫本頁) 510900 經濟部智慧財產局員工消費合作社印製 A7 B7 五、發明說明（p) (3 „ 0 0克，SK 8 β毫莫耳）及吡啶（4 β 0毫升，4 9 · 3毫莫耳5 5當量）之二氯甲烷（2 4毫升）冰水溶液滴加入甲磺醒氯（〗.14毫升，14.8毫莫耳，165當量）。於室溫下攪拌38小時後移除冰浴，結合以水（15D毫升），以 10%HC]酸化，並以***萃取。結合萃取液並以食鹽水洗〇加入矽_並移除溶劑。將吸附物驟層析（45/55 石油醚/乙酸乙酯）可得標題化合物之白色固體 (3 0 · 2 克，8 0%) ： NMR (CDC13); δ 8.30 (s, 1H), 7.90 (d, J = 8 Hz, 1H), 7.50-7.40 (m, 5H), 7.38-7.28 (m, 1H), 3.26 (s, 3H), 2.50 (s, 3H), 1.61 (s, 3H). 例1 1 牢碭酸-4 - ( 9 - - 2 > 3 -二串赛駢「2… 3 _ b Ί - 8宗- d -莘、於含甲磺酸-4 ~ ( 2， 3 _二甲萘駢[2， 3 - b卜瞎吩-4 -基） -苯酯（3 . 0 0克，7 · 8 4毫莫耳），四氫呋喃（3 1 · 5毫升）， 80%乙酸（16毫升）及濃硫酸（（K87毫升）中，於室温下加入碘Μ…5 9克，6 · 2 7毫莫耳，0 · 8當量）及碘酸（〇 · 4 1 4 克，2·35毫莫耳，0·9當量）。於室溫下攪拌12天。倒至稀釋亞硫酸氫銷溶液（ 2 0 0毫升），並以***（ 2 x 2 0 0毫升）萃取。結合萃取液祓加入矽_。移除溶劑，將吸附驟層析（9 0 / 1 0石油醚/乙酸乙酯）。純化以Η P L C可得原料（3 0 · 5 % ) 及標題化合物之白色固體（0 · 8 3 5克，3 0 % ):熔點2 1 2 - 213°C; NMR (DMSO-d6); δ 8.09 (d, J = 8 Hz, 1H), 7.64-7.58 (m, 1H), 7.54-7.42 (m, 5H), 7.43 (d, J = 8 Hz, 1H), 3.47 (s, 3H, S03CH3), 2.42 (s, 3H), 1.50 (s, 3H); MS(EI): [M+] 508 (100%); Anal. calc, for C21H17I03S2, C, 49.61, H, 3.37, N, 0.00. Found: C, 49.44, H, 3.52, N, 0.03. _82_ 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) > 1_0 A7 B7 五、發明說明（卜内及室溫下滴加入含溴（β · 1 1 4毫升，2 · 2 1毫莫耳）之冰醋_ (2.50毫升）。完全溶解後出現沈澱。欖拌2小時後 (請先閱讀背面之注意事項再填寫本頁) ，以稀釋亞硫酸氫鈉溶液中止反應，加至水（1 〇〇毫升）Example R Acetic acid 4-(2.3-di idler f 2. 3-b 1-blind hope j-even ·)-Rong ester Add acetic anhydride (0.68 ml, 7.20 mmol) to 4_ (2 , 3-Dimethyl Rape [2, 3-b〗 -blind powder-4 -based> ~ touch (2 · 0 g, g · 57 7 mol) cough late (8 · (5 ml) stirring An aqueous solution of ice. After 17 hours, add to the precipitate collected by filtration, wash with 5% HC1, wash with water, and grind with ether. Dry under vacuum to obtain the title compound as a white solid (1.99 g, 88%): Point 14 -1 5 0 ° C: NMR (DMSO-d6); δ 8.49 (s, 1H), 7.94 (d, J = 8 Hz,-79-) This paper size applies the Chinese National Standard (CNS) A4 specification (210 χ 297 mm) " a ~ -------------------- Order --------- line (Please read the precautions on the back before filling This page) 510900 Α7 Β7 V. Description of the invention (70 (please read the notes on the back before filling this page) 1H), 7.46 (ddd, J = 8, 6, 2, 1H), 7.38 (ddd, J = 8, 1, 1 Hz, 1H), 7.39-7.34 (m, 2H), 7.28 (d, J = 8 Hz, 2H), 6.90 (d, J = 9 Hz, 2H), 2.40 (d, J = 1 Hz, 3H), 2.34 (s, 3H), 1.57 (d, J = 1 Hz, 3H); MS (El): 346 (90%, MI), 304 (100%) ; Anal. Calc, for C22H1802S: C, 76.27, H, 5.34, N. 0.00. Found: C, 75.88, H. 5.04, N, 0.28. Example? M a- (-2. 3-: Second trial "2 * 3-hi -mm -4-¾) _: -Examination Jl-Dichloromethane (9 ml in 15 minutes and 9 ml of η e 3 2 fi ml) In the dark, dropwise to acetic acid 4-ί 2, 3-dimethylnaphthalene [2, 3-b] -benzophen-4 -yl) -phenyl ester (1 · 8 7 g, 5 j 1 mmol) and dichloromethane (47 ml) of iron (III) chloride (50 mg, 0β 31 mmol). After 10 minutes, add a dilute solution of hydrogen sulfite and The layers were separated in water and diethyl ether. The diethyl ether layer was washed with brine and concentrated to give the title compound as a white solid (2.09 g, 91%): melting point 190-1 91: NMR (DMSO-d6); 8.20 (d, J = 8 Hz, 1H), 7.65 (ddd, J = 8, 7, 1, 1H), 7.49 (ddd, J = 8, 7, 1 Hz, 1H), 7.43-7.38 (m, 1H) , 7.40 (d, J = 9 Hz, 2H), 7.30 (d, J = 9 Hz, 2H), 2.43 (d, J = 1 Hz, 3H), 2.33 (s, 3H), 1.55 (d, J = 1 Hz, 3H); MS (El): 1 bromine isotope pattern; 424 (95%, MI), 426 (100%); Anal. Calc, for C22H17 Br02S: C, 62.12, H, 4.03, N, 0.00. Found: C, 62.46, H, 4.05, N, 0Ό9. Example 8 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 4-(9-湟 -2 · 3 -: Ι: φ ^ SI Γ 2. 3-b 1-g: take P points-4-even)-add potassium hydroxide solution (6.0 ml, 6.G millimolar) to room temperature Stired 4-(9 -bromo-2,3-dinaphthalenepyrene [2, 3-b] -blazepan 4-yl) -phenyl ester (0.48 g, 1.14 mmol) at THFC 15 ml) / methanol (0 ml). After 1 hour, remove the organic solvent and add water, ~ 80 ~ This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 510900 Printed by the Consumers ’Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Explanation (79) Acidified with 10% HC1. The obtained solid was washed with water and milled with acetamidine, and dried under vacuum to obtain the title compound as a white solid (0.32 g, 73%): melting point 165-: NMR (DMSO-d6 ); S9.68 (s, 1Η), 8.17 (d, J = 8 Hz, 1H), 7.62 (ddd, J = 8, 6, 1 Hz; 1H), 7.50 (d, J = 8 Hz, 1H) , 7.44 (ddd, J = 8, 7, 1 Hz, 1H), 7.13 (d, J = 9 Hz, 2H), 6.91 (d, J = 9 Hz, 2H), 2.42 (d, J = 1 Hz, 3H), 1.59 (d, J = 1 Hz, 3H); MS (El): 1 bromine isotope pattern 382 (95%, MI), 384 (100%); Anal. Calc, for C20H15BrOS: C, 62.67, H , 3.95, N, 0.00. Found: C, 62.40, H, 3.91, N, 0.09. Example 9?-6-dibromo-4 di (9-瘪 -2 * 3 -two-string 萦 1¾ 「2 · 3 -h Ί-瞎盼-4-）)-g # Add bromine ((K34 ml, 5 · 4 mmol) acetic acid (5 ml), stir 4- (9-bromo-2, 3-dimethylform [2,3-b] -blphen-4- Phenol (1.10 g, 2.87 millimolar potassium acetate (2.82 g, 28.7 mol) and acetic acid (31 mL) solution. After 5 hours, add water (2 GQ mL) and a small amount of sodium sulphate solid. Filter and solid Washed with water, milled with ethyl acetate, and dried under vacuum to obtain the title compound as a white solid (1 β 5 2 g, 88%): melting point 172-174 ° C: NMR (DMSOd6); 11.95 (broad s, 1Η), 10.20 (broad s, 1H), 8.19 (ddd, J = 8,1,1 Hz, 1H), 7.65 (ddd, J = 8, 6, 1 Hz, 1H), 7.59 (s, 2H), 7.51-7.49 (m, 2H), 2.44 (d, J = 1 Hz, 3H), 1.90 (s, 3H), 1.64 (d, J = 1 Hz, 3H); MS (+ FAB): 3 bromine isotope pattern 538 (40 %), 540 (100%), 542 (90%), 544 (50%); Anal. Calc, for C22H13Br30S C2H402: C, 43.95, H, 2.85, N, 0.00. Found: C, 44.13, H, 2.66 , N, 0.12. Example] 0 g—Xinyi Jl—Two AII—j—Lt · —S Two—IL · · Li—Dong—MJ12_, 3 _b Ί ~ hope-4 _ group) _-¾ ester Containing 4-(2,3 -Dinaphthylpyrene [2,3 -b 时时粉 -4-基) © &81; 81- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ) ----— II ---------- 丨丨 Order · -------- ^^^ 1 (Please (Please read the notes on the back before filling this page) 510900 Printed by A7 B7, Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of invention (p) (3 „0 0 g, SK 8 β millimolar) and pyridine (4 β 0 ml, 4 9 · 3 mmoles of 5 5 equivalents) of dichloromethane (24 ml) of ice-water solution was added dropwise to methanesulfonic acid chloride (.14 ml, 14.8 mmoles, 165 equivalents). After stirring at room temperature for 38 hours, the ice bath was removed, combined with water (15D ml), acidified with 10% HC], and extracted with ether. The extracts were combined and washed with brine. Silica was added and the solvent was removed. The adsorbate was subjected to flash chromatography (45/55 petroleum ether / ethyl acetate) to obtain the title compound as a white solid (30. 2 g, 80%): NMR (CDC13); δ 8.30 (s, 1H), 7.90 (d, J = 8 Hz, 1H), 7.50-7.40 (m, 5H), 7.38-7.28 (m, 1H), 3.26 (s, 3H), 2.50 (s, 3H), 1.61 (s, 3H). Example 1 1 Ranoic acid-4-(9--2 > 3-Erlian match 骈 "2… 3 _ b Ί-8 cases-d-莘, containing methanesulfonic acid-4 ~ (2, 3 _ Dimethylnaphthalene [2, 3-b-benzophen-4-yl)-phenyl ester (3.0 g, 7.84 mmol), tetrahydrofuran (31. 5 ml), 80% acetic acid ( 16 ml) and concentrated sulfuric acid (K87 ml), iodine M ... 59 g, 6.27 mmol, 0.8 equivalent) and iodic acid (0.414 g, 2. 35 millimoles, 0.9 equivalents). Stir at room temperature for 12 days. Pour into dilute hydrogen sulfite solution (200 ml) and extract with ether (2 x 2000 ml). Combine the extracts矽 Add silicon 。. Remove the solvent and perform adsorption chromatography (90/10 petroleum ether / ethyl acetate). Purify with Η PLC to obtain the raw material (30.5%) and the title compound as a white solid (08 3 5 g, 30%): melting point 2 1 2-213 ° C; NMR (DMSO-d6); δ 8.09 (d, J = 8 Hz, 1H), 7.64-7.58 (m, 1H), 7.54 -7.42 (m, 5H), 7.43 (d, J = 8 Hz, 1H), 3.47 (s, 3H, S03CH3), 2.42 (s, 3H), 1.50 (s, 3H); MS (EI): (M + ] 508 (100%); Anal. Calc, for C21H17I03S2, C, 49.61, H, 3.37, N, 0.00. Found: C, 49.44, H, 3.52, N, 0.03. _82_ This paper standard applies to China National Standard (CNS ) A4 size (210 X 297 mm) -------------------- Order --------- line (Please read the precautions on the back before Fill out this page) > 1_0 A7 B7 V. Description of the invention (add bromine (β · 114 ml, 2.21 mmol) ice vinegar (2.50 ml) at room temperature and at room temperature. Precipitation occurred after complete dissolution. After 2 hours of mixing (please read the precautions on the back before filling this page), stop the reaction by diluting the sodium bisulfite solution, and add to water (1000 ml)

中，以10%HC1酸化，並以***萃取。將萃取液水洗，分層5輿矽_靜置過夜並移除溶劑。將趿附物驟層析（90 / 1 〇石油醚/乙酸乙酯），可得標題化合物之摻白色固髑 (0.391¾ , 58%) ： NMR (DMSO-d6); δ 10.25 (s, 1H, OH), 8.42 (d, J =8 Hz, 1H), 7.65 (s,^2H), 7.60-7.47 (m, 3H), 7.247.19 (m, 3H), 7.15-7.00 (m, 2H), 2.39 (s, 3H), 1.62 (s, 3H). 例1 4 乙醱4 一（ 9 _湟· 2 -氛甲基_ 3 _甲基養駢丄2 i 3-bl -瞎盼-4二基丄二i.盟一It was acidified with 10% HC1 and extracted with ether. The extract was washed with water, the layers were separated and left to stand overnight and the solvent was removed. Chromatography of the tritium appendix (90/10 petroleum ether / ethyl acetate) gave the title compound as a white solid (0.391¾, 58%): NMR (DMSO-d6); δ 10.25 (s, 1H , OH), 8.42 (d, J = 8 Hz, 1H), 7.65 (s, ^ 2H), 7.60-7.47 (m, 3H), 7.247.19 (m, 3H), 7.15-7.00 (m, 2H) , 2.39 (s, 3H), 1.62 (s, 3H). Example 1 4 Acetyl-4-a Two bases two i. League one

於含4 - (9-溴-2，3-二甲萘駢[2，3-b卜睹盼-4-基）-苯酯（4. 0 0克，9. 4毫莫耳）之無水二氯甲烷（41毫升）冰水溶液，於1 0分内滴加入亞磺醯氯（Q · 7 6毫升，1 0 · 3毫莫耳）。於冰浴下攪拌1小時後，以水（1㈣毫升）中止反應並以 ***稀釋。過濾後分層。加入矽_至有機層後移除溶劑。將吸附物驟層析（9 0 / 1 0〜8 0 / 2 0石油醚/乙酸乙酯）可得標題化合物之白色固體（2 . 5 7克，5 9 % ) : NMR (DMSO-d6);S 經濟部智慧財產局員工消費合作社印製 8.23 (d, J = 8 Hz, 1H), 7.71 (dd, J = 8,1 Hz, 1H), 7.55-7.43 (m, 4H), 7.33-7.30 (m, 2H), 5.09 (s, 2H), 2.34 (s, 3H), 1.66 (s, 3H). m is 4 -《9 -淳-3~审某_2-嗎游木-4-某)_-甲奈撤__[_2_t—3_i_b丄-陵— 粉―:―4_ 二基—Jr_M_ - 84- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印製 510900 A7 _B7_ 五、發明說明（〇 ) 將含乙酸4 - ( 9 _溴-2 -氯甲基-3 -甲基萘駢[2， 3 - b卜嗦盼-4 ~基）-苯酯（1 . 2 0克，2 β 6 1毫莫耳）之無水N s N -二甲基甲醯胺U 2毫升）Λ，於室溫及乾氮氣下加入含磺酸鉀 (L 08克5 7 t 83毫莫耳，3當量）及嗎啉（0 · 6 8 3毫升，7 · 83 毫莫耳，3當量）。攪拌1 .? 5小時後加入另1當量嗎啉 (0 . 2 2 7毫升），而0 . 5小時後加入另2當量嗎啉（0 . 5毫升）。攪拌1小時，以水（1 2 5毫升）稀釋，將有機層以***萃取（4 (11]毫升）。分層並加入矽膠至有機層。移除溶劑，將趿附物驟層析（7 4 / 2 5〜7 0 / 3 Q石油醚/乙酸乙酯）可得標題化合物之白色固體（1 · 〇〇克，82%):熔點2 5 0 - 251°C; NMR (DMSO-d6); δ 9.69 (s, 1H), 8.18 (d, J = 8 Hz, 1H), 7.63 (ddd,1 J= 8,7,1 Hz, 1H), 7.51-7.42 (m, 2H), 7.13 (d, J=8 Hz, 2H), 6.91 (d, J = 8 Hz, 2H), 3.71 (s, 2H), 3.60 (t, J = 5 Hz, 4H), 2.50-2.48 (m, 4H), 1.65 (s, 3H); MS (El): [M+], 1 溴同位素式樣，467 (10%), 469 (10%); Anal· Calc for C24H22BrN02S: C， 61.53, H, 4.73, N, 2,99. Found: C, 61.53, H, 4.88, N, 3.01. 例16 4 -（ 9 -淳- 2 -二乙胺甲某- 3 -申某-寨駢F 2 > 3 - b Ί -瞟盼-4 - 某）-乙鹽將含4 - ( 9 -溴-2 -氯甲基-3 -甲基萘駢[2， 3 - b卜睹吩 - 4 -基）-乙酸鹽（1 β 2 7克，2 · 7 6毫莫耳）及磺酸钾（1 · 1 4 6 克，8 . 2 3毫莫耳，3當量）之無水Ν，Ν -二甲基甲醯胺（1 5 毫升），於室温及乾氮氣下加入二甲胺（（Κ 8 6毫升，8 β 2 9 毫莫耳）。攪拌3小時後再加入二甲胺（〇 . 5毫升，4 . 83 毫莫耳），於室溫下攪拌3小時後貯於-1 4 °C下過夜。於室溫下攪拌5小時後以水（1 Q0毫升）稀釋。將有機層以 -85- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂·-------- (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 ____ B7 五、發明說明（^ ) 乙《萃取。結合萃取液，加入矽膠並移除溶劑。將吸附 _驟層析（8 5 /〗5〜8 0 / 2 0石油醚/乙酸乙酯）可得標題化合物之黃色固體（〇 · 3 3 2 克，2 6 % ) : NMR (CHC13); δ 8.29 (d，J = 8Anhydrous containing 4-(9-bromo-2,3-dimethylnaphthalenepyrene [2,3-b bupanpan-4-yl) -phenyl ester (4.0 g, 9.4 mmol) A solution of dichloromethane (41 ml) in ice was added dropwise over 10 minutes to add sulfinyl chloride (Q · 76 ml, 10 · 3 mmol). After stirring in an ice bath for 1 hour, the reaction was quenched with water (1 ml) and diluted with ether. Layered after filtering. Remove the solvent after adding silicon to the organic layer. The adsorbate was subjected to flash chromatography (9 0/1 0 to 8 0/2 petroleum ether / ethyl acetate) to obtain the title compound as a white solid (2.57 g, 59%): NMR (DMSO-d6) ; S Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economy 8.23 (d, J = 8 Hz, 1H), 7.71 (dd, J = 8,1 Hz, 1H), 7.55-7.43 (m, 4H), 7.33-7.30 (m, 2H), 5.09 (s, 2H), 2.34 (s, 3H), 1.66 (s, 3H). ) _- Kinai __ [_ 2_t—3_i_b 丄 -ling—Feng——: ―4_ Erji—Jr_M_-84- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) Wisdom of the Ministry of Economic Affairs Printed by the Consumer Cooperative of the Property Bureau 510900 A7 _B7_ V. Description of the invention (〇) Acetic acid 4-(9 _ bromo-2 -chloromethyl-3 -methylnaphthalene 骈 [2, 3-b 卜嗦 -4 ~ Yl) -phenyl ester (1.20 g, 2 β 6 1 mmol) anhydrous N s N -dimethylformamide U 2 ml) Λ, add sulfonic acid at room temperature under dry nitrogen Potassium (L 08 g 5 7 t 83 millimoles, 3 equivalents) and morpholine (0.68 3 milliliters, 7.83 millimoles, 3 equivalents). After stirring for 1.5 hours, another equivalent of morpholine (0.227 ml) was added, and after 0.5 hours, another equivalent of morpholine (0.5 ml) was added. Stir for 1 hour, dilute with water (125 ml), extract the organic layer with diethyl ether (4 (11) ml). Separate the layers and add silicone to the organic layer. Remove the solvent and chromatographically attach the condensate (7 4/2 5 ~ 7 0/3 Q petroleum ether / ethyl acetate) to obtain the title compound as a white solid (1.0 g, 82%): melting point 2 50-251 ° C; NMR (DMSO-d6) ; δ 9.69 (s, 1H), 8.18 (d, J = 8 Hz, 1H), 7.63 (ddd, 1 J = 8,7,1 Hz, 1H), 7.51-7.42 (m, 2H), 7.13 (d , J = 8 Hz, 2H), 6.91 (d, J = 8 Hz, 2H), 3.71 (s, 2H), 3.60 (t, J = 5 Hz, 4H), 2.50-2.48 (m, 4H), 1.65 (s, 3H); MS (El): [M +], 1 bromine isotope pattern, 467 (10%), 469 (10%); Anal · Calc for C24H22BrN02S: C, 61.53, H, 4.73, N, 2, 99. Found: C, 61.53, H, 4.88, N, 3.01. Example 16 4-(9-Chun-2-Diethylamine A-3-Shenmou-Village F 2 > 3-b Ί-瞟Pan-4-a-) salt will contain 4-(9 -bromo-2 -chloromethyl-3 -methylnaphthalene hydrazone [2, 3-b phenyl-4 -yl) -acetate (1 β 27 grams, 2.76 millimoles) and potassium sulfonate (1.146 grams, 8.23 millimoles, 3 equivalents) of anhydrous N, N-dimethylformamide Amine (15 ml), dimethylamine (K 8 6 ml, 8 β 2 9 mmol) was added at room temperature under dry nitrogen. After stirring for 3 hours, dimethylamine (0.5 ml, 4. 5 ml) was added. 83 mmol), stirred at room temperature for 3 hours, and stored at -14 ° C overnight. After stirring at room temperature for 5 hours, diluted with water (1 Q0 ml). The organic layer was -85- Standards are applicable to China National Standard (CNS) A4 specifications (210 X 297 mm) -------------------- Order · -------- (please first Read the notes on the back and fill in this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 ____ B7 V. Description of the Invention (^) B "Extraction. Combine the extraction solution, add silicone and remove the solvent. Will adsorb _ step Chromatography (8 5 / 〖5 ~ 80/20 petroleum ether / ethyl acetate) gave the title compound as a yellow solid (0.332 g, 26%): NMR (CHC13); δ 8.29 (d , J = 8

Hz，1H)，7.54-7.51 (m，2H)，7.36-7.30 (m，1H)，7·20 (d，J =8 Hz，2H)，6·96 (m， 2H), 3.90-3.65 (broads, 2H), 2.80-2.45 (broads, 4H), 1.69 (s, 3H), 1.26-1.00 (broad s, 6H); MS (El): M+ WL 453 有一溴！，301 (58%)，302 (16%), 303 (7%), 382 (100%), 383 (54%), 384 (14%), 453 (30%), 455 (30%); MS [(+)ESI]: [M + H] = 496(65%)，1 溴同位素式樣；高解離 MS: Calc. Sample Mass: 496.09459 for Formula C25H31N303C1 [M + H], Measured Mass: 496.09407, Mass deviation: 0.52 mmu; Anal. Calc, for C24H24BrNOS: C, 63.43, H, 5.32, N, 3.08. Found: C, 62.33, H, 5.11, N, 2.75. 例17 4-Z-LJ二jj—- 2 '二乙胺申甚-3 -甲某-着駢「2 . 3 - h 1 -瞎盼-4 - 基)_____~ 8¾ 將含4 - ( 9 -溴-2 -二乙胺甲基-3 -甲基-黎駢[2，3 - b ] -睹吩-4 -基）-乙酸鹽（〇 · 6 7 6克，〗β 3 6毫莫耳）之四氫呋喃 (18毫升）及甲醇（12毫升），於室溫下滴加入Κ0Η溶液（1Ν ，1 · 毫升）。攪拌1小時後移除溶劑。結合以水（50毫升）並酸化以1 (U H C 1。將有機不純物以***萃取而殘留白色固體於二層中^過濾粘狀固體，碾製以乙酸並濃縮。將標題化合物1之鹽溶於四氫呋喃及甲醇，並結合以飽和重磺酸鈉。攪拌2 Q分後，以水稀釋後再攪拌1 0分。將有機層以 ***萃取。將***層以食鹽水洗，濃縮可得標題化合犓之黃色固體（〇 · 4 9 克，7 9 % ) Μ E. ( D M S 0 - d 6 ; 9 · 6 9 ( s， 1H, OH), 8.18 (d, J = 8 Hz, 1H), 7.63-7.59 (m, 1H), 7.51-7.43 (m, 2H), 7.14 (d, J =8 Hz, 2H), 6.91 (d, J = 8 Hz, 2H), 3.73 (s, 2H), 2.58-2.50 (m, 4H), 1.63 (s, 3H), 1.01 (t, J=7 Hz, 6H). -8 G - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂--------- (請先閱讀背面之注意事項再填寫本頁) 510900 A7 __B7_ 五、發明說明（K ) 例1 8 2 · P> - 二漳-4 -（ 9 -淳-2 '二乙胺某-3 -申某-縈酣「2 · 3 - b 1 (請先閱讀背面之注意事項再填寫本頁) 二!!室」分_—二_4二―基」_____-齡將含4 - ( 9 -溴-2 -二乙胺甲基-3 -甲基-萘駢[2 , 3 - b卜 »#盼-4 -基）-酚（Q · 4 6 2克，】· 0 7毫莫耳），9 /】.冰醋酸 /水（1 〇毫升）溶液加至含溴（0 · 1 1 5毫升，2 . 2 4毫莫耳 ,2 · 2當鼍）之9 / 1冰醋酸/水（4毫升）溶液。攪拌1 · 5 小時後以稀釋亞硫酸氫鈉溶液中止反應，再以水稀釋後以***萃取。將不溶固體倒至三角瓶，於***中攪拌過夜。移除乙醱，將固體（（K 1 6 2克，0 · 2 6 5毫莫耳）溶於四氫呋喃（1 〇〇毫升），滴加入1 N n a 0 Η ( 0 · 2 6 5毫升， 0 „265毫莫耳）。攪拌20分後移除溶劑，攪拌以水（100 毫升）。倒除水，將殘漬攪拌以石油醚過夜。移除溶劑。將殘渣溶於四氫呋喃/***，加入矽膠。移除溶將趿附物驟層析（75/25石油醚/乙酸乙酯），可得標題化合敉之白色固體（0 · U 3克，1 7 % ) : ( D M S 0 - 經濟部智慧財產局員工消費合作社印製 d6); δ 10.3-10.1 (broad s, 1H, OH), 8.20 (d, J = 8 Hz, 1H), 7.66-7.63 (m, 1H), 7.60 (s，2H)，7·50-7·48 (m，2H)，3.76 (s，2H)，3.28-2.60 (m，4H)，1.02 (t，J = 7 Hz, 6H); MS +FAB: M+ @ M/Z 609/611/613/615 3 bromine pattern 536 (22%)，538 (68%)， 540 (80%), 541 (52%), 611 (22%), 613 (22%); Anal. Calc, for C24H22Br3NOS: C, 47.08, H, 3.62, N, 2.29. Found: C, 47.21, H, 3.69, N, 2.21. m is 2 ,______6 -—一淳- 4 ~ ( 9 -淳- 3 -甲某_ 2 -碟縣- 4 -某申备 F 2 ·> 3 - b Ί - 8 拿盼- 4 -某）-齡將含4-(9-溴-3-甲基-2-嗎啉~4-基甲萘駢[2，3_b]-Hz, 1H), 7.54-7.51 (m, 2H), 7.36-7.30 (m, 1H), 7.20 (d, J = 8 Hz, 2H), 6.96 (m, 2H), 3.90-3.65 ( broads, 2H), 2.80-2.45 (broads, 4H), 1.69 (s, 3H), 1.26-1.00 (broad s, 6H); MS (El): M + WL 453 has a bromine! , 301 (58%), 302 (16%), 303 (7%), 382 (100%), 383 (54%), 384 (14%), 453 (30%), 455 (30%); MS [(+) ESI]: [M + H] = 496 (65%), 1 bromine isotope pattern; high dissociation MS: Calc. Sample Mass: 496.09459 for Formula C25H31N303C1 [M + H], Measured Mass: 496.09407, Mass deviation : 0.52 mmu; Anal. Calc, for C24H24BrNOS: C, 63.43, H, 5.32, N, 3.08. Found: C, 62.33, H, 5.11, N, 2.75. Example 17 4-Z-LJ 二 jj—- 2 ' Diethylamine Shengan-3 -A-Mou-Zhu 骈「2. 3-h 1 -Baipan-4 -yl) _____ ~ 8¾ will contain 4-(9 -bromo-2 -diethylamine methyl-3- Methyl-tribenzyl [2,3-b] -phenphen-4 -yl) -acetate (0.66 g, β 3 6 mmol) tetrahydrofuran (18 ml) and methanol (12 ml ), K0Η solution (1N, 1 · ml) was added dropwise at room temperature. The solvent was removed after stirring for 1 hour. Combined with water (50ml) and acidified to 1 (UHC 1. The organic impurities were extracted with ether and remained white The solid was in two layers. The sticky solid was filtered, milled with acetic acid, and concentrated. The salt of the title compound 1 was dissolved in tetrahydrofuran and methanol, and combined with saturated heavy sulfonic acid. Sodium. After stirring for 2 Q minutes, diluting with water and then stirring for 10 minutes. The organic layer was extracted with ether. The ether layer was washed with brine and concentrated to give the title compound as a yellow solid (0.49 g, 7 9 %) M E. (DMS 0-d 6; 9 · 6 9 (s, 1H, OH), 8.18 (d, J = 8 Hz, 1H), 7.63-7.59 (m, 1H), 7.51-7.43 (m , 2H), 7.14 (d, J = 8 Hz, 2H), 6.91 (d, J = 8 Hz, 2H), 3.73 (s, 2H), 2.58-2.50 (m, 4H), 1.63 (s, 3H) , 1.01 (t, J = 7 Hz, 6H). -8 G-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) -------------- ------ Order --------- (Please read the notes on the back before filling out this page) 510900 A7 __B7_ V. Description of Invention (K) Example 1 8 2 · P >-Erzhang- 4-(9 -chun-2 'diethylamine a certain -3-Shenmou-萦酣 "2 · 3-b 1 (please read the precautions on the back before filling this page) two room" points _-two _4 di-yl "_____- year-old will contain 4-(9 -bromo-2 -diethylaminemethyl-3 -methyl-naphthalene [2, 3 -b» # hope-4 -yl) -phenol (Q · 4 62 g,] · 0 7 mmol), 9 /]. Add glacial acetic acid / water (10 ml) solution to bromine 0 * 115 ml, 2. 24 mmol, 2.2 When the lizard) of 9/1 glacial acetic acid / water (4 ml). After stirring for 1.5 hours, the reaction was stopped with a dilute sodium bisulfite solution, and then diluted with water and extracted with ether. Pour insoluble solids into a Erlenmeyer flask and stir in ether overnight. The acetamidine was removed, and the solid ((K 162 g, 0.265 mmol) was dissolved in tetrahydrofuran (100 ml), and 1 N na 0 Η (0 · 2 6 5 ml, 0 "265 millimoles". After stirring for 20 minutes, remove the solvent and stir with water (100 ml). Pour off the water and stir the residue with petroleum ether overnight. Remove the solvent. Dissolve the residue in tetrahydrofuran / ether and add silicone 。 Remove the chromatographic method (75/25 petroleum ether / ethyl acetate) to obtain the title compound as a white solid (0 · U 3 g, 17%): (DMS 0-Ministry of Economic Affairs Printed by employee property cooperative of property bureau d6); δ 10.3-10.1 (broad s, 1H, OH), 8.20 (d, J = 8 Hz, 1H), 7.66-7.63 (m, 1H), 7.60 (s, 2H) , 7.50-7 · 48 (m, 2H), 3.76 (s, 2H), 3.28-2.60 (m, 4H), 1.02 (t, J = 7 Hz, 6H); MS + FAB: M + @ M / Z 609/611/613/615 3 bromine pattern 536 (22%), 538 (68%), 540 (80%), 541 (52%), 611 (22%), 613 (22%); Anal. Calc , for C24H22Br3NOS: C, 47.08, H, 3.62, N, 2.29. Found: C, 47.21, H, 3.69, N, 2.21. m is 2, ______ 6 ----- Ishun- 4 ~ (9 -Shun- 3-甲Some_ 2 -disc County-4-An application F 2 · > 3-b Ί-8 Napan-4-a) -year-old will contain 4- (9-bromo-3-methyl-2-morpholine ~ 4-ylmethyl Naphthalene 骈 [2,3_b]-

H 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） >10900 A7 〜_____B7___ 五、發明說明（舄） (請先閱讀背面之注意事項再填寫本頁) 吩-4 -基）-酚（0 · 8 5 4克，1 · 8 2毫莫耳）之9 /】.乙酸/水 (1 7毫升：）溶液加入含溴（0 · 2 E) 7毫升，4 . 0 1毫莫耳）之 9 / 1乙酸/水（1毫升）溶液。攪拌3小時後以水稀釋 (2 (HI毫升），以***萃取數次。集合萃取液，濃縮 _追加以苯可得標題化合物之黃色固體（1 · 1 8克）：熔點 2 3 7 - 2 4 0 °C : N M R (吡啶-d 5 ) ; (5 8 · 4 3 ( d d，J = 8 · 1 Η z ) 1Η)，7·81 (s，2Η)，7·71 (d，J = 8 Ηζ，1Η)，7·62 (m，1Η)，7·50 (m，1Η)，6.20 - 5·30 (broad s，1H), 3.78 (t，J = 5 Hz，4H)，3.70 (s，2H)，2.55 (t，J=4 Hz，4H)，1·78 (s, 3H); MS (El): [M+]，3 溴同位素式樣，622 (8%). 624 (18%). 626(1 叫). 628(8%); Anal· Calc, for C24H20Br3NO2S:C，46.03, H，3.22, N，2·24· Found: C, 45.07, H, 3.31, N, 2.05. 例20 iji—UL二漠—- 2」——3:二甲基-養駢 F 2 . 3 - b 1 -睹盼-4 -某）- 2 - 磁1 將乙醇（4 0毫升）加至含4 - ( 9 -溴_ 2，3 _二甲基-萘駢 [2, 3-b]-B寒吩-4-基）-0¾ (1·98克，5.17毫莫耳）及硝酸鐵七水合物（2 ·() 9克，5 . 1 7毫莫耳），將所得暗籃色瀋液於4 5 °C油浴中加熱1 4小時。加入稀釋H C1並以***萃取。加入矽_至***層並移除溶劑。將吸附物驟層析（9 5 / 5石油_/乙酸乙酯）可得標題化合物之橘色固體（1 . 6 3克，經濟部智慧財產局員工消費合作社印製 7 4 1):熔點 1 8 3 - 1 8 5 °C : NMR (DMS0-d6); δ 11.31 (s，1Η)，8.21 (d，J = 8 Hz，1H)，7.85 (d，J = 2 Hz，1 Η)，7·66 (ddd，J = 8, 6, 1 Hz，1H)，7.54 (dd，J = 8, 2 Hz, 1H), 7.48 (dd, J = 7, 1 Hz, 1H), 7.29 (d, J = 8 Hz, 1H), 6.91 (d, J = 9 Hz, 2H), 2.44 (d, J = 1 Hz，3H), 1.61 (d, J = 1 Hz, 3H); MS (El): 1 溴同位素式樣 i 427 (95%, MI), 429 (100%); Anal. Calc, for C20H14BrNO3S: C, 56.09, H, 3.29, N, 3.27. Found: C, 55.55, H, 3.15, N, 3.23. -88- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 B7 五、發明說明（Μ ) 例2 1 ， ^追-在-（Q -漳- 2 · 3 -二田甚-苯_ Γ 2 · 3 - bl-睹盼- 4 -基） (請先閱讀背面之注意事項再填寫本頁) -R -磁齡將含溴（ο β 〇 4 0毫升，0 · 7 5 6毫莫耳）之乙酸（〇 · 5毫升）滴加至含4 - ( 9 -溴-2，3 -二甲基-葉駢[2 , 3 - b卜睹盼-4 -基）-2 -硝齡（0 · 2 0克，0 · 4 6 7毫莫耳），乙酸郵 (0.2 2 8克，2.3 3 5毫莫耳）之乙酸（4-乙酸鉀。10分後，加入水並以***萃取。加入矽_至***層並移除溶劑。將趿附物驟層析（9 5 / 5〜8 4 / 1 5 )可得標題化合物之黃色固體（0 · 1 4 1 克，6 0 % ):熔點 1 2 9 - 1 3 0 °C : N M R ( D M S 0 - d 6 ) ; <ϊ 11.30 (s, 1H), 8.22 (d, J = 8 Hz, 1H), 8.03 (s, 1H), 7.96 (s, 1H), 7.67 (quintuplet, J =4 Hz, 1H)，7·51 (d，J = 4 Hz, 2H), 2·45 (s, 3H)，1.65 (s，3H); MS (El): 2 溴同位素式樣 505 (40%), 507 (100%), 509 (50%); Anal. Calc, for C20H13Br2NO3S: C, 47.36, H, 2.58, N, 2.76. Found: C, 47.18, H, 2.55, N, 2.63. 例22 ?· -胺某- 4 -（ 9 -溴- 2 . 3 -二申某-馨駢「2 , 3 - h 1 - Ilf 盼- 4 - 某）-酚仿T e t · L e 11 · 1 9 9 0， 1 1 8卜Π 8 2之方法，將蒙脫土 K 1 0 ( 4 2 5毫克）加至含4- ( 9-溴-2，3-二甲基-萦駢 [2，3 - b卜瞎盼-4 -基-2 -硝酚（0 · 6 Q 8克，1 · 4 2毫莫耳）經濟部智慧財產局員工消費合作社印製 ,無水肼（0 · 2 7 6 # 1，8 · 9 5毫莫耳）及乙醇（4 · 2毫升） ,加熱至8 5 °C 3 0分。冷卻至室溫·>加入水並以乙醜萃取〇乾燥***並濃縮可得標題化合物之白色固體（0 · 5 7 6克 ,10 0%):熔點 1?3- 175°C : NMR(DMSO-d6);59.26 (s，1H), -89-本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 B7 五、發明說明（以） (請先閱讀背面之注意事項再填寫本頁) 8.14 (dd, J = 8, 1 Hz, 1H), 7.63-7.58 (m, 2 Η), 7.42 (ddd, J = 8, 6, 1 Hz, 1H), 6.78 (d, J = 8 Hz, 1H), 6.54 (d, J = 2 Hz, 1H), 6.35 (dd, J = 8, 2 Hz, 1H), 4.67 (broad s, 2H), 2.42 (s, 3H), 1·69 (s，3H); MS (+FAB): 1 溴同位素式樣 398 (30%， M+H), 400 (30%, M+H); Anal. Calc, for C20H16BrNOS: C, 60.31, H, 4.05, N, 3.52; Found: C, 61.36, H, 4.08, N, 3.25. 例23 2 -拜安某-6 - $阜-4 - ( Q - - 2 · 3 -二甲基-赛駢「2 · 3 - h Ί - B靠盼-4 -某) -齡仿 T e t …I」e 11 · 1 9 9 G，1 1 8 1 - 1 1 8 2 之方法，將蒙脫土 K 1 0 ( 1 · 4 克）加至含2 -溴-4 - ( 9 -溴-2，3 -二甲基-萘駢[2，3 - b ] - 1Φ 盼-4-基）-2-硝酚（1.2克，2.37毫莫耳），無水阱（1毫升）及乙醇（7 J毫升），加熱至8 5 °C 6 0分。冷卻至室溫並濃縮 ^驟層析二次（第一次溶離以***，第二次溶離以4 : 1石油醚/乙酸乙酯）可得標題化合物之白色固體（0 .? 4 1克， 66%): NMR (DMSO-d6); δ 8.16 (ddd, J = 8, 1, 1 Hz, 1H), 7.65-7.60 (m, 2 H), 7.47 (ddd, J = 8, 6, 1 Hz, 1H), 6.65 (d, J = 2 Hz, 1H), 6.57 (d, J = 2 Hz, 1H), 2.43 (d, J =1 Hz, 3H), 1.73 (d, J = 1 Hz, 3H); MS (El): 2 溴同位素式樣 475 (50%, M+H), 477 (100%, M+H), 479 (50%, M+H); Anal. Calc, for C20H15Br2NOS: C, 50.34, H, 3.17, N, 2.94. Found: C, 51.35, H, 3.35, N, 2.72. 例24 F 海- 4 - ( 9 -漳 - 2 · 3 -二 g 甚-赛駢「2 * 3 - b 卜蹿 B分-4 - 經濟部智慧財產局員工消費合作社印製某）-2 -勰茱氳某1 _乙酴將溴乙酸甲酯（0.15毫升，1.58毫莫耳）加至含磺酸鉀（0.228克，1.61毫莫耳），2-溴-4-(9-溴-2，3-二甲基-萘駢[2，3-b]-瞎吩-4-基）-2-硝齡（0.40克， 0 . 7 8 9毫莫耳）之DMF ( 2 · 8毫升）。15小時後，將反應 -9 0 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 B7 五、發明說明（朽）液加至水妝以乙_萃取。加入矽顧至***層並移除溶劑。將吸附物驟層析（9 : 1石油醚/乙酸乙酯）可得標題化 (請先閱讀背面之注意事項再填寫本頁) 合物之黃色固體（0 · 3 0 5克，6 7 % )。將固體（G · Q 5 0克， 0.0 8 6毫莫耳）溶於l:iTHF:甲醇（2毫升），處理以KOH溶液 (1 J N，0 · 3 0毫升，〇 · 3 〇毫莫耳）。2 5分後，以水稀釋，酸化以10%HC1並以乙_萃取。將***層乾燥（硫酸鈉），濃縮並由石油_/乙_再結晶可得標題化合物之白色固體 (0 , 0 2 5 克，5 11):熔點 2 2 8 - 2 2 9 °C : NMR (DMSO-d6); δ 8·23 (d，J = 9H This paper size is in accordance with China National Standard (CNS) A4 (210 X 297 mm) > 10900 A7 ~ _____ B7___ V. Description of the invention (舄) (Please read the notes on the back before filling this page) ) -Phenol (0.84 5g, 1.82 mmol) 9 /]. Acetic acid / water (17 ml :) solution was added 7 ml bromine (0. 2 E), 4.0 1 mmol) of a 9/1 acetic acid / water (1 ml) solution. After stirring for 3 hours, it was diluted with water (2 (HI ml), and extracted with ether several times. The extracts were collected, concentrated and added with benzene to obtain the title compound as a yellow solid (1.88 g): melting point 2 3 7-2 4 0 ° C: NMR (pyridine-d 5); (5 8 · 4 3 (dd, J = 8 · 1 Η z) 1Η), 7.81 (s, 2Η), 7.71 (d, J = 8 Ηζ, 1Η), 7.62 (m, 1Η), 7.50 (m, 1Η), 6.20-5.30 (broad s, 1H), 3.78 (t, J = 5 Hz, 4H), 3.70 ( s, 2H), 2.55 (t, J = 4 Hz, 4H), 1.78 (s, 3H); MS (El): [M +], 3 bromine isotope pattern, 622 (8%). 624 (18% ). 626 (1 call). 628 (8%); Anal · Calc, for C24H20Br3NO2S: C, 46.03, H, 3.22, N, 2.24 · Found: C, 45.07, H, 3.31, N, 2.05. Example 20 iji—UL Ermo—- 2 ″ —— 3: Dimethyl-Nanyang F 2. 3-b 1-Jianpan-4-a)-2-Magnetic 1 Add ethanol (40 ml) to the containing 4-(9 -bromo_ 2,3_dimethyl-naphthalenepyrene [2, 3-b] -B cold phen-4-yl) -0¾ (1.98 g, 5.17 mmol) and ferric nitrate Hydrate (2 · () 9 g, 5.17 mmol), and the resulting dark basket-colored sediment was heated in an oil bath at 45 ° C for 14 hours. Diluted H C1 was added and extracted with ether. Add silicon to the ether layer and remove the solvent. Chromatography of the adsorbate (9 5/5 petroleum _ / ethyl acetate) to obtain the title compound as an orange solid (1.63 g, printed by the Consumers' Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 7 4 1): melting point 1 8 3-1 8 5 ° C: NMR (DMS0-d6); δ 11.31 (s, 1Η), 8.21 (d, J = 8 Hz, 1H), 7.85 (d, J = 2 Hz, 1 Η), 7 66 (ddd, J = 8, 6, 1 Hz, 1H), 7.54 (dd, J = 8, 2 Hz, 1H), 7.48 (dd, J = 7, 1 Hz, 1H), 7.29 (d, J = 8 Hz, 1H), 6.91 (d, J = 9 Hz, 2H), 2.44 (d, J = 1 Hz, 3H), 1.61 (d, J = 1 Hz, 3H); MS (El): 1 bromine Isotopic pattern i 427 (95%, MI), 429 (100%); Anal. Calc, for C20H14BrNO3S: C, 56.09, H, 3.29, N, 3.27. Found: C, 55.55, H, 3.15, N, 3.23. -88- This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 510900 A7 B7 V. Description of the invention (M) Example 21, ^ 追-在-(Q-张-2 · 3- Nita-benzene_ Γ 2 · 3-bl-watchpan- 4 -based) (Please read the notes on the back before filling out this page) -R-Magnetic age will contain bromine (ο β 〇4 0mL, 0 · 7 5 6 mmol) acetic acid (0.5 ml) was added dropwise to a solution containing 4-( 9-bromo-2,3-dimethyl-phyllene [2, 3 -b bupan-4 -yl) -2-nitrate (0.20 g, 0.467 mol), Acetic acid (0.2 28 grams, 2.35 millimoles) in acetic acid (potassium 4-acetate. After 10 minutes, water was added and extracted with ether. Silicon was added to the ether layer and the solvent was removed. The attachment was snapped Chromatography (9 5/5 to 8 4/1 5) gave the title compound as a yellow solid (0 · 14 1 g, 60%): melting point 1 2 9-1 3 0 ° C: NMR (DMS 0- d 6); < ϊ 11.30 (s, 1H), 8.22 (d, J = 8 Hz, 1H), 8.03 (s, 1H), 7.96 (s, 1H), 7.67 (quintuplet, J = 4 Hz, 1H ), 7.51 (d, J = 4 Hz, 2H), 2.45 (s, 3H), 1.65 (s, 3H); MS (El): 2 bromine isotope pattern 505 (40%), 507 (100 %), 509 (50%); Anal. Calc, for C20H13Br2NO3S: C, 47.36, H, 2.58, N, 2.76. Found: C, 47.18, H, 2.55, N, 2.63. Example 22? 4-(9 -bromo- 2. 3 -Dishen-Xin-"2, 3-h 1-Ilfant-4--) -phenol-like T et · L e 11 · 1 9 9 0, 1 1 8 According to the method of Bu 82, montmorillonite K 1 0 (4.5 mg) was added to the solution containing 4- (9-bromo-2,3-dimethyl-fluorene [2,3 -b] Pan-4 -Base-2 -Nitrophenol (0 · 6 Q 8 g, 1 · 4 2 mmol) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, anhydrous hydrazine (0 · 2 7 6 # 1, 8 · 95 mmol) and ethanol (4.2 ml), heated to 85 ° C for 30 minutes. Cool to room temperature. &Gt; Add water and extract with ethyl acetate. Dry the ether and concentrate to obtain the title compound as a white solid (0.576 g, 100%): melting point 1 to 3-175 ° C: NMR ( DMSO-d6); 59.26 (s, 1H), -89- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 510900 A7 B7 V. Description of the invention (with) (Please read the back Please fill in this page again) 8.14 (dd, J = 8, 1 Hz, 1H), 7.63-7.58 (m, 2 Η), 7.42 (ddd, J = 8, 6, 1 Hz, 1H), 6.78 (d , J = 8 Hz, 1H), 6.54 (d, J = 2 Hz, 1H), 6.35 (dd, J = 8, 2 Hz, 1H), 4.67 (broad s, 2H), 2.42 (s, 3H), 1.69 (s, 3H); MS (+ FAB): 1 bromine isotope pattern 398 (30%, M + H), 400 (30%, M + H); Anal. Calc, for C20H16BrNOS: C, 60.31, H, 4.05, N, 3.52; Found: C, 61.36, H, 4.08, N, 3.25. Example 23 2-Bai Anmou-6-$ fu-4-(Q--2 · 3-dimethyl-sai骈「2 · 3-h Ί-B 靠 hope-4-a)-age imitation T et… I」 e 11 · 1 9 9 G, 1 1 8 1-1 1 8 2 1 0 (1.4 g) was added to the compound containing 2-bromo-4-(9 -bromo-2,3-dimethyl-naphthalenepyrene [2,3-b]-1Φ 4-Base) -2-nitrophenol (1.2 g, 2.37 mmol), without a water trap (1 ml) and ethanol (7 J ml), heated to 8 5 ° C for 60 minutes. Cool to room temperature and concentrate. ^ Chromatographic chromatography twice (first dissolution with ether, second dissolution with 4: 1 petroleum ether / ethyl acetate) to obtain the title compound as a white solid (0.41 g, 66%): NMR (DMSO-d6); δ 8.16 (ddd, J = 8, 1, 1 Hz, 1H), 7.65-7.60 (m, 2 H), 7.47 (ddd, J = 8, 6, 1 Hz , 1H), 6.65 (d, J = 2 Hz, 1H), 6.57 (d, J = 2 Hz, 1H), 2.43 (d, J = 1 Hz, 3H), 1.73 (d, J = 1 Hz, 3H ); MS (El): 2 bromine isotope pattern 475 (50%, M + H), 477 (100%, M + H), 479 (50%, M + H); Anal. Calc, for C20H15Br2NOS: C, 50.34, H, 3.17, N, 2.94. Found: C, 51.35, H, 3.35, N, 2.72. Example 24 F Hai- 4-(9 -Zhang- 2 · 3 -Two g or even Saisai "2 * 3 -b BU 蹿 B -4-Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs) -2-Fructus Corni 1 _Ethyl bromide methyl bromide (0.15 ml, 1.58 mmol) Potassium acid (0.228 g, 1.61 mmol), 2-bromo-4- (9-bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] -benzophen-4-yl) -2 -DMF (2.8 ml) of nitrate age (0.40 g, 0.79 mmol). After 15 hours, the reaction will be -90. Chinese National Standard (CNS) A4 specification (210 X 297 mm) 510900 A7 B7 V. Description of the invention (deterioration) Liquid is added to water makeup for extraction. Add silicon to the ether layer and remove the solvent. Remove the adsorbed substance. Chromatography (9: 1 petroleum ether / ethyl acetate) gave the title (please read the precautions on the back before filling this page). The compound was a yellow solid (0.35 g, 67%). The solid (G · Q 50 g, 0.086 6 mol) was dissolved in 1: iTHF: methanol (2 ml) and treated with a KOH solution (1 JN, 0.30 ml, 0.3 mol). After 25 minutes, it was diluted with water, acidified with 10% HC1 and extracted with ethyl acetate. The ether layer was dried (sodium sulfate), concentrated and recrystallized from petroleum / ethyl acetate to give the title compound as a white solid (0, 0 2 5 g, 5 11): melting point 2 2 8-2 2 9 ° C: NMR (DMSO-d6); δ 8 · 23 (d, J = 9

Hz，1H)，8.14 (d，J = 2 Hz，1H), 8·04 (d，J = 2 Hz，1Η)，7.69 (ddd，J = 8, 7, 1， 1H)，7.54 (ddd, J = 8, 7, 1 Hz, 1H)，7.48 (d，J = 8 Hz，1H)，4.87 (d，J == 6 Hz，1H)， 4.82 (d，J = 6 Hz, 1H)，2.46 (s，3H)，1.62 (s，3H); MS (+FAB): 2 溴同位素式樣 563 (40%)，565 (100%)，567 (50%); Anal. Calc, for C22H15Br2N05S: C， 46.75, H，2.68, N, 2.48· Found: C，45.18, H，2.66, N，2.38. 例25 m.二·2二~ 茱丙葡 _ 酯將市售可得（S)~2 -經基-3-苯丙酸（5.Q克，30.1毫莫耳）及對甲苯磺酸水合犓（1克）之甲醇（丨2 5毫升），使用3 A分子篩回流除去水1 7小時。濃縮後溶於***。將***溶液以飽和電碩酸鈉溶液及食鹽水洗，濃縮可得標題化合物之白色固體 (5 ‘ 3 2 克，9 8 % ) : NMR (CDC13); δ 7.36-7.20 (m，5H)，4.47 (ddd，J = 5, 6, 7 Hz，經濟部智慧財產局員工消費合作社印製 1H), 3.78 (s, 3H), 3.14 (dd, J = 5, 14 Hz, 1H), 2.97 ( dd, J = 7, 14 Hz), 2.69 (d, J = 6Hz, 1H). m 2 6 (i)_ - 2 -「4 -磘苄醣甚Ί - 4 -茱丁乙酯於泳浴下將市售可得U )胃2 -羥基-4 _苯丁酸乙酯（1 · 8 6 ~ 9 1 ~ 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印製 510900 A7 B7Hz, 1H), 8.14 (d, J = 2 Hz, 1H), 8.04 (d, J = 2 Hz, 1Η), 7.69 (ddd, J = 8, 7, 1, 1H), 7.54 (ddd, J = 8, 7, 1 Hz, 1H), 7.48 (d, J = 8 Hz, 1H), 4.87 (d, J == 6 Hz, 1H), 4.82 (d, J = 6 Hz, 1H), 2.46 (s, 3H), 1.62 (s, 3H); MS (+ FAB): 2 bromine isotope pattern 563 (40%), 565 (100%), 567 (50%); Anal. Calc, for C22H15Br2N05S: C, 46.75, H, 2.68, N, 2.48 · Found: C, 45.18, H, 2.66, N, 2.38. Example 25 m. Di · 2 · 2 ~ Ethyl glucoside will be commercially available (S) ~ 2-Warp Phenyl-3-phenylpropanoic acid (5.Q g, 30.1 mmol) and methanol (2.5 ml) with hydrazone (1 g) of p-toluenesulfonic acid, water was removed using a 3 A molecular sieve under reflux for 17 hours. After concentration, it was dissolved in ether. The ether solution was washed with a saturated sodium electrous solution and brine, and concentrated to obtain the title compound as a white solid (5'32 g, 98%): NMR (CDC13); δ 7.36-7.20 (m, 5H), 4.47 (ddd, J = 5, 6, 7 Hz, printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economy, 1H), 3.78 (s, 3H), 3.14 (dd, J = 5, 14 Hz, 1H), 2.97 (dd, J = 7, 14 Hz), 2.69 (d, J = 6Hz, 1H) .m 2 6 (i) _-2-"4-磘 Benzylose Ί-4 -Jude ethyl ester will be marketed under the swimming bath Available for sale U) Stomach 2-Hydroxy-4 _ ethyl phenylbutyrate (1.86 ~ 9 1 ~ This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) Intellectual Property Bureau, Ministry of Economic Affairs Printed by Employee Consumer Cooperative 510900 A7 B7

五、發明說明（9M 毫升，9 . 6 0毫莫耳），對硝苄酸（6 · 4 2克，3 8 · 4毫莫耳， 4當量）及三苯瞵（1G· 07克，38 .4毫莫耳，4當量）之無水四氫呋喃（Η 0毫升），於4 0分期間並保持内部溫度 4〜5 °C下滴加入偶氮二羧酸二乙酯（6 · 0 5毫升，3 8 · 4毫莫耳，4當量）。於4〜5 °C下攪拌1小時後移除冰浴，靜置於室溫下5天。移除溶劑後溶於***及乙酸乙酯（6 0 0 毫升）。加入矽_ (20 0毫升）後移除溶劑。將吸附物驟層析（8 0 / 2 ti〜7 0 / 3 0石油醚/乙酸乙酯）可得標題化合物之黃色油（4 · 0 3 克）：NMR (CDC13); δ 8·30 (d，J = 9Hz，2H), 8.18 (d，J = 9Hz, 2H), 7·38 - 7.18(m，5H), 5·28 (t, J = 2Hz, 1H)· 4·23(η, J = 7Hz, 2H), 2.85 (t, J = 8Hz, 2H), 2.40 - 2.33 (m, 2H), 1.29 (t, J = 7H, 3H); MS [ (+) FAB]: [M +H] m/z = 358. 例27 (S ) -镡某-4 -茱丁酴乙酯將氰酸鉀（〇 · 1 7 6克，2 · 7 D毫莫耳）之絶對酒精（4 3 毫升），於3 0分期間滴加入含（S ) - 2 - [ 4 -硝苄醯基] -4 -苯丁酸甲酯（3 · 8 6克，1 0 · 8毫莫耳）之絶對酒精 (3 8毫升）^攪拌2 · 25小時後移除溶劑，以水稀釋並以稀H C I酸化。以***萃取。結合萃取液，加入矽膠 (6 0毫升）移除溶劑。將吸附物驟層析（9 ·· 1〜8 / 2石油醚/乙酸乙酯），溶劑追加以苯可得標題化合物之黃色油 < 1 . 6 7 克，7 4 % ) : NMR (CDC13); δ 7·38 - 7.16 (m，5Η)， 4·30 - 4.10(m，3H)，2·9 - 2.6 (m，3H，)，2.2 - 1.9(m，2H)，1.15(t，4Hz，3H); [a]25D +178.23 at 10.98mg/mL CHC13. -9 2 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 A7 B7 五、發明說明（9 1 ) 丄-幻心:2 L2·. · ·['二漳-4 - ( 9 -溴-2 · 3 -二 g 某-% 駢「2 * 3-bl 二gliiL二4 -基）-茱氳甚1 - 3 -茱某丙酴酯將偶氮二羧酸二乙酯（Ο β 2 6 2毫升，1 · 6 7毫莫耳），於室溫下滴加至含2，6 -二溴-4 - ( 9 -溴-2，3 -二甲基-赛駢[2，3-b卜瞎盼-4-基）-酚（0·6ϋ克，1·11毫莫耳）及（S ) - 2 -羥基- 3 _苯丙酸甲酯（0 · 3克，1 · 6 7毫莫耳），三苯瞵U) · 4 3 7克，1 · 6 7毫莫耳）及苯（5毫升）之攬容液，於8 (! °C油浴下加熱G小時。冷卻至室溫，以乙 ®稀釋並加入矽膠（3 0毫升）。濃縮並將趿附物驟層析 (9 5 : 5石油醚/乙酸乙酯）可得標題化合物之白色固體 (〇 7 6 克，9 7 % ):熔點 1 7 4 - 1 7 5 °C : N M R ( D M S 0 - d 6 ) ; ί 8.21 (ddd, J = 8,1,1 Hz, 1H), 7.74 (d, J = 2 Hz, 1H), 7.73 (d, J = 2 Hz, 1H),7.67 (ddd, J = 8, 6, 1 Hz, 1H), 7.53 (ddd, J = 8, 7, 1 Hz, 1H), 7,43 (d, J= 8Hz, 1H), 7.35-7.24 (m, 5H), 5.11 (dd, J = 7, 6 Hz, 1H), 3.61 (s, 3H), 3.43 (dd, 13, 6 Hz, 1H), 3.40 (dd, 13, 7 Hz, 1H), 2.44 (d, J = 1 Hz, 3H), 1.60 (d, J = 1 Hz, 3H); MS (+FAB)·· 3 溴同位素式樣 700(20%)，702 (70%)，704 (75%), 706 (25%); Anal· Calc· for C30H23Br3O3S: C, 51.23, H，3·30, N，0·00· Found: C，51.52, Η， 3.36, N, 0.12. m 2 8 (—[)-2- Γ2 , 6 '二遼-4 -（ 9 -淳、2 · 3 二甲某-養駢「2 · 3 - b Ί -瞎盼-4 -某）-茉鐘：甚]-3 -茱丙醵將K0H溶液（1·0Ν，2.0毫升，2.0毫莫耳）加至含（R) -2 [ 2 9 6 -二溴-4 - ( 9 -溴-2，3 -二甲基-萘駢[2 , 3 - b ] -瞎吩-4 -基）-苯氧基]-3 -苯基丙酸甲酯（0 · 6 9 9克， -93- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） -------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 510900 A7 B7_ 五、發明說明（9>) (請先閱讀背面之注意事項再填寫本頁) 0.99毫莫耳）之THF(12毫升）/甲醇（7毫升）。3小時後濃縮，以水稀釋並酸化以10%HC1。過濾，水洗並以石油_碾製，真空乾燥可得標題化合物之白色固體 (0 · 6 4 5 克，9 4 % ) : [a]D25=+14.29。（8·75 mg/mL CHC13); NMR (DMSO-d6); δ 8.19 (d，J = 8 Hz, 1H)，7.66 (ddd，J = 8, 7, 1 Hz, 1H)，7.61 (s， 2H), 7.52 (ddd, J = 8, 7, 1 Hz, 1H), 7.41 (d, J = 8Hz, 1H), 738-7.20 (m, 5H), 5.27 (t, J = 7 Hz, 1H), 3.37 (dd, 14, 6 Hz, 1H), 3.28 (dd, 14, 7 Hz, 1H), 2.43 (s, 3H), 1·59 (s，3H); MS (+FAB): 3 溴同位素式樣 686 (20%)，688 (75%)，690 (75%), 692 (25%); Anal. Calc, for C29H21Br303S: C, 50,53, H, 3.07, N, 0.00. Found: C, 50.04, H, 3.11, N, 0.05. 例3 0 (R) - 2「2 · ft -二？馨一4 一（ 9 - $意一2 · 3 -二 g 某一着駢「2 · 3 ~ b 1 -蹿盼-4 -某）-茱氤甚1 -丙麟將 2 3 6 -二溴-4 - ( 9 -漠-2，3 -二甲基-綦駢[2， 3 - b ]- 瞎吩-4 -基）-酚（0 · 3 0克，0 · 5 5 4毫莫耳），市售可得 (S - ( - ) ~乳酸甲酯（0 8 0 7 9毫升，0 · 8 3 1毫莫耳）及三苯_ ( 0 · 2 1 8克，0 · 8 3 1毫莫耳）之無水苯（5毫升），經濟部智慧財產局員工消費合作社印製於室溫及於1 G分期間，於乾氮氣下滴加入偶氮二羧酸二乙_( Π · 1 3 1毫升，0 . 8 3 1毫莫耳）。加熱回流4小時再於室溫下攪拌2 4小時。以***稀釋並結合以矽_。移除溶雨後將吸附物驟層析（？5/25石油醚/二氯甲烷）可得白色固體（0 · 2 8 3克，8 1 % )。將含此固體（0 · 2 6克，0 · 4 1 5 毫莫耳）之四氫呋喃（9毫升）及甲醇（3毫升）於室溫滴规入Κ0Η溶液（IN，（Κ 4 9 8毫升，0·4 9 8毫莫耳）。攪拌1.5 小時後移除溶劑。結合以水並酸化以10%HC1。加入***， _ 9 4 _ I紙張尺度適用中國國家標準（CNS)A4規格（210>< 297公釐） _ 510900 經濟部智慧財產局員工消費合作社印製 A7 __B7_ _ 五、發明說明（％) 攪拌1 〇分並充份混合後分層。將有機層以食鹽水洗，濃縮，並追加以石油醚可得標題化合物之白色固體（〇 . 2 5 7克， 9 9%):熔點 2 2 4 - 2 2 5 °C : NMR (DMSO-d6); δ 13.09-13.06 (broad s, 1H， COOH), 8.20 (d, J = 8 Hz, 1H), 7.75 (s, 2H), 7.67 (ddd, J = 8, 7, 1 Hz, 1H), 7.55-7.47 (m，2H)，5.02 (q, J= 7 Hz, 1H)，2.44 (s, 3H)，1.62 (s，3H,)，1.56 (d, J = 6 Hz, 311);1^(+?仙):[14+]，3漠同位素式樣，609.7 (30%)，611.8(75%)，613.8 (100%), 615.7 (35%);高解離 MS [(FAB)+ve] Calc Sample mass for C23H17Br303S: 609.84485, measured mass 609.85789, mass deviation 13.04 mmu. Anal. Calc, for C23H17Br303S: C, 45.05, H, 2.79, N, 0.00. Found: C, 44.30, H, 2.69, N, 0.38. 例31 X. Sl„ ^2__[ 2 , 6'二溴-4- (9 -淳-2· 3 -二申某-赛駢 Γ2. - hi -g索盼-4 -某）-茱氩某1 - 4 -荣丁酴仿例3 0之方法，由2，6 -二溴-4 - ( 9 -溴-2， 3 -二甲基- 萘駢[2，3-b卜噠盼-4-基卜酚（例9)及市售可得（R卜2-羥基- 4 -苯丁酸乙酯可製得白色固體：熔點1 7 6 - 1 7 7°C : [ a ] 25/D = +7.58° (10.692 mg/mL, CHC13); NMR (DMSO-d6); δ 13.0 (broad s, 1H, COOH)，8.21 (ddd，J = 8, 7，1 Hz, 1H)，7·73 (s，2H)，7.67 (ddd，J = 8, 7, 1 Hz， 1H)，7·52 (ddd, J = 8, 7，1 Hz, 1H), 7.46 (m，1H)，7.32-7.28 (m，2H), 7.24-7.18 (m,3H), 5.03 (t, J = 6 Hz, 1H), 2.95 (m, 1H), 2.72 (m, 1H), 2.44 (s, 3H), 2.28 (m,2H), 1.61 (s, 3H); MS (+FAB): [M+], 3 溴同位素式樣，700 (30%)， 702(100%), 704 (75%), 706 706(40%); Anal. Calc, for C30H23Br3O3S: C, 51.23, H3.30, N 0.00. Found: C, 51.15, H, 3.13, N, 0.00. 例32 —(E_) 2「^， 6 -二淳-4 - ( 9 - ?赛- 2 . 3 -—--密~~基,衆__Bf __L2_*—3—: b 1, -H窜盼-4 -某）-茱舊，某1 - 4 -茱丁酴仿例3 0之方法，由2，6 _二溴-4 - ( 9 -溴-2， 3 -二甲基- 萘駢[2，3 - b卜瞎盼-4 -基）-酚（例9 )及（S ) - 2 -羥基-4 -苯丁 - 95- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） -------------------訂--------- (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7_ 五、發明說明（94 ) 酸乙酯（洌27)可製得白色固體：[a]25/D = -12.187° (9.929 mg/mL, CHC13); NMR (DMSO-d6); δ 13·24 (s，1H)，8.21 (d，J = 8 Hz, 1H), 7·73 (s, 2Η), 7.67 (ddd, J = 8, 7, 1 Hz, 1H), 7.52-7.45 (m, 2H), 7.32-7.28 (mt 2H), 7.24-7.20 (m, 3H) 5.02 (d, J = 6Hz, 1H), 2.99-2.86 (m, 1H), 2.75-2.65 (m, 1H), 2.45 (s, 3H), 2.30-2.20 (m, 2H), 1.61 (s, 3H); MS (+FAB): [M+], 3 溴同位素式樣 700 (30%), 702 (100%), 704 (90%), 706 (55%); Anal. Calc, for C30H23Br3O3S: C, 51.23, H, 3.30, N, 0.00. Found: C, 51.33. H, 3.33, N, 0.29. 例33 —LJLI—J—二二溴-4-(2, 二田某- 9-¾ 礒鶸某-赛駢「2 * 3 - b H家盼-4 -某）-荣氛某1 - 3 -茉丙躜仿例3 0之方法，由2， 6 -二溴-4 - ( 2 , 3 -二甲基-9 -苯磺醯基-萘駢[2，3 - b卜瞎吩-4 -基）-酚（例1 3 )及（S ) -2-羥基-3-苯丙酸甲酯（例25)可製得白色固體：opt . rot. [a]25/D = +22.84° (10.068 mg/mL, CHC13); NMR (DMSO-d6); δ 13.13 (broad s, 1H), 8.42 (d, J = 8 Hz, 1H), 7.75 (t, J = 2 Hz, 2H), 7.58 (ddd, J = 8, 7, 1 Hz, 1H), 7.50 (ddd, J = 8, 7, 1 Hz, 1H), 7.44 (d, J = 8 Hz, 1H), 7.37-7.19 (m, 7H), 7.15-7.11 (m, 1H), 7.03-7.00 (m, 2H), 5.22 (t, J = 7 Hz, 1H), 3.37-3.28 (m, 2H), 2.39 (s, 3H), 1.62 (s, 3H); MS (El): [M+], 2 溴同位素式樣，716 (10%), 718 (20%), 720 (10%); Anal. Calc, for C35H26Br203S2: C, 58.50, H, 3.65, N, 0.00. Found: C, 58.77, H, 3.94, N, 0.16. 例34 __~ 2「2 * 6 -二淳-4 -（ 2 *__3~二甲基苯磋酿基-赛酣「2 , 3 - h Ί -嗦盼-4 -某）-茱氫基1 -丙酴仿例3 0之方法，由2，G -二溴-4 - ( 2 , 3 -二甲基-9 -苯磺醯基-萘駢[2 5 3 - b卜Bt盼-4 -基）-酚（例1 3 )及市售可得（S )V. Description of the invention (9M ml, 9.60 mmol), p-nitrobenzic acid (6.42 g, 38.4 mmol, 4 equivalents) and triphenylhydrazone (1G · 07 g, 38 .4 mmol, 4 equivalents) of anhydrous tetrahydrofuran (Η0 ml), and diethyl azodicarboxylate (6.05 ml, 3 8 · 4 millimoles, 4 equivalents). After stirring at 4 ~ 5 ° C for 1 hour, the ice bath was removed and left at room temperature for 5 days. After removing the solvent, it was dissolved in ether and ethyl acetate (600 ml). Remove the solvent after adding silicon (200 ml). The adsorbate was subjected to flash chromatography (80/2 ti ~ 7 0/30 petroleum ether / ethyl acetate) to obtain the title compound as a yellow oil (4.03 g): NMR (CDC13); δ 8 · 30 ( d, J = 9Hz, 2H), 8.18 (d, J = 9Hz, 2H), 7.38-7.18 (m, 5H), 5.28 (t, J = 2Hz, 1H) · 4 · 23 (η, J = 7Hz, 2H), 2.85 (t, J = 8Hz, 2H), 2.40-2.33 (m, 2H), 1.29 (t, J = 7H, 3H); MS [(+) FAB]: (M + H ] m / z = 358. Example 27 (S)-Ethyl-4-Judeoyl ethyl acetate will be potassium cyanate (0.176 g, 2. 7 D mmol) absolute alcohol (4.3 ml ), Absolute alcohol containing (S)-2-[4 -nitrobenzyl] -4-phenylbutyric acid methyl ester (3.86 g, 10 · 8 mmol) was added dropwise during 30 minutes. (38 ml) ^ After stirring for 2.25 hours, the solvent was removed, diluted with water and acidified with dilute HCI. Extract with ether. Combine the extracts and add silicone (60 ml) to remove the solvent. The adsorbate was subjected to flash chromatography (9 ·· 1 ~ 8/2 petroleum ether / ethyl acetate), and the solvent was added with benzene to obtain a yellow oil of the title compound (1.67 g, 74%): NMR (CDC13 ); δ 7.38-7.16 (m, 5Η), 4.30-4.10 (m, 3H), 2.9-2.6 (m, 3H,), 2.2-1.9 (m, 2H), 1.15 (t, 4Hz, 3H); [a] 25D +178.23 at 10.98mg / mL CHC13. -9 2-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) --------- ----------- Order --------- line (Please read the notes on the back before filling this page) Printed by the Consumers' Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Explanation (9 1) 丄 -phantasmal heart: 2 L2 ·. · · ['Erzhang-4-(9 -bromo-2 · 3 -dig some-% 骈 "2 * 3-bl digliiL di 4 -based ) -Fructus Corni 1-3-Fructus Cornifoliate Diethyl azodicarboxylate (0 β 2 6 2 ml, 1. 67 mmol) is added dropwise at room temperature to 2 containing 6-Dibromo-4-(9 -bromo-2,3-dimethyl-cybidine [2,3-b bublend-4-yl) -phenol (0.6 g, 1.11 mmol) ) And (S)-2 -hydroxy-3-phenylpropanoic acid methyl ester (0.3 g, 1.67 mmol), three Benzene (U) · 4 3 7 g, 1. 67 mmol) and benzene (5 ml) in a volumetric solution, heated in an 8 (! ° C oil bath for G hours. Cool to room temperature, and use B® Dilute and add silica gel (30 ml). Concentrate and perform chromatography on the appendix (95: 5 petroleum ether / ethyl acetate) to obtain the title compound as a white solid (07 g, 97%): melting point 1 7 4-1 7 5 ° C: NMR (DMS 0-d 6); ί 8.21 (ddd, J = 8,1,1 Hz, 1H), 7.74 (d, J = 2 Hz, 1H), 7.73 ( d, J = 2 Hz, 1H), 7.67 (ddd, J = 8, 6, 1 Hz, 1H), 7.53 (ddd, J = 8, 7, 1 Hz, 1H), 7,43 (d, J = 8Hz, 1H), 7.35-7.24 (m, 5H), 5.11 (dd, J = 7, 6 Hz, 1H), 3.61 (s, 3H), 3.43 (dd, 13, 6 Hz, 1H), 3.40 (dd , 13, 7 Hz, 1H), 2.44 (d, J = 1 Hz, 3H), 1.60 (d, J = 1 Hz, 3H); MS (+ FAB) ·· 3 bromine isotope pattern 700 (20%), 702 (70%), 704 (75%), 706 (25%); Anal · Calc · for C30H23Br3O3S: C, 51.23, H, 3.30, N, 0 · 00 · Found: C, 51.52, Η, 3.36 , N, 0.12. M 2 8 (— [)-2- Γ2, 6 'Eliao-4-(9-Chun, 2 · 3 Dijiamou-raise 骈 "2 · 3-b Ί-盼盼 -4 -A)-Jasmine: even] -3 Add KOH solution (1.0N, 2.0 ml, 2.0 mmol) to (R) -2 [2 9 6 -dibromo-4-(9 -bromo-2,3-dimethyl-naphthalene) [ 2, 3-b] -benzophen-4 -yl) -phenoxy] -3 -phenylpropanoic acid methyl ester (0.69 g, -93-) This paper size is applicable to Chinese National Standard (CNS) A4 Specifications (210 X 297 mm) ------------------- Order --------- Line (Please read the precautions on the back before filling this page ) 510900 A7 B7_ V. Description of the invention (9 >) (Please read the precautions on the back before filling out this page) 0.99 mol) of THF (12 ml) / methanol (7 ml). After 3 hours it was concentrated, diluted with water and acidified to 10% HC1. Filtration, washing with water and milling with petroleum, and drying under vacuum gave the title compound as a white solid (0.64 g, 94%): [a] D25 = + 14.29. (8 · 75 mg / mL CHC13); NMR (DMSO-d6); δ 8.19 (d, J = 8 Hz, 1H), 7.66 (ddd, J = 8, 7, 1 Hz, 1H), 7.61 (s, 2H), 7.52 (ddd, J = 8, 7, 1 Hz, 1H), 7.41 (d, J = 8Hz, 1H), 738-7.20 (m, 5H), 5.27 (t, J = 7 Hz, 1H) , 3.37 (dd, 14, 6 Hz, 1H), 3.28 (dd, 14, 7 Hz, 1H), 2.43 (s, 3H), 1.59 (s, 3H); MS (+ FAB): 3 bromine isotope Style 686 (20%), 688 (75%), 690 (75%), 692 (25%); Anal. Calc, for C29H21Br303S: C, 50,53, H, 3.07, N, 0.00. Found: C, 50.04, H, 3.11, N, 0.05. Example 3 0 (R)-2 "2 · ft-two? Xin one 4 one (9-$ 意一 2 · 3-two g somewhere" 2 · 3 ~ b 1 -Pan-4 -a) -Fructus Corni 1-Proline 2 3 6 -Dibromo-4-(9 -Mo-2,3 -dimethyl-pyrene [2, 3-b] -Blphen-4 -yl) -phenol (0.30 g, 0.54 5 mmol), commercially available (S-(-) ~ methyl lactate (0 8 0 7 9 ml, 0 · 8 3 1 mol) and triphenyl_ (0 · 2 1 8 g, 0 · 8 3 1 mol) anhydrous benzene (5 ml), printed at room temperature by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs And dropwise under dry nitrogen during 1 G minutes Diethyl azodicarboxylate ((1.13 ml, 0.83 1 mmol). Heat to reflux for 4 hours and then stir at room temperature for 24 hours. Dilute with ether and combine with silicon. After removing the dissolved rain, the adsorbate was subjected to flash chromatography (? 5/25 petroleum ether / dichloromethane) to obtain a white solid (0.232 g, 81%). This solid (0.26 g, 0 · 4 1 5 mmol) tetrahydrofuran (9 ml) and methanol (3 ml) dropwise into a KO solution (IN, (K 4 9 8 ml, 0.4 9 8 mmol) at room temperature. Stir 1.5 Remove solvent after hours. Combine with water and acidify to 10% HC1. Add ether, _ 9 4 _ I paper size applies Chinese National Standard (CNS) A4 specification (210 > < 297 mm) _ 510900 Intellectual Property of Ministry of Economic Affairs Printed by the Consumer Cooperative of the Bureau A7 __B7_ _ V. Description of the Invention (%) Stir for 10 minutes and mix thoroughly after layering. The organic layer was washed with brine, concentrated, and added with petroleum ether to give the title compound as a white solid (0.257 g, 99%): melting point 2 2 4-2 2 5 ° C: NMR (DMSO-d6 ); δ 13.09-13.06 (broad s, 1H, COOH), 8.20 (d, J = 8 Hz, 1H), 7.75 (s, 2H), 7.67 (ddd, J = 8, 7, 1 Hz, 1H), 7.55-7.47 (m, 2H), 5.02 (q, J = 7 Hz, 1H), 2.44 (s, 3H), 1.62 (s, 3H,), 1.56 (d, J = 6 Hz, 311); 1 ^ (+? Sen): [14+], 3 Mo isotopes, 609.7 (30%), 611.8 (75%), 613.8 (100%), 615.7 (35%); high dissociation MS [(FAB) + ve] Calc Sample mass for C23H17Br303S: 609.84485, measured mass 609.85789, mass deviation 13.04 mmu. Anal. Calc, for C23H17Br303S: C, 45.05, H, 2.79, N, 0.00. Found: C, 44.30, H, 2.69, N, 0.38. Example 31 X. Sl „^ 2 __ [2, 6 'dibromo-4- (9 -Chun-2 · 3 -Eshenmou-sai 骈 Γ2.-Hi -g Sopan-4 -mou)-Zhu Armou 1-4-Rong Dingjing method of Example 3 0, from 2,6-dibromo-4-(9 -bromo-2,3-dimethyl-naphthalene hydrazone [2,3-b -Gibbol (Example 9) and commercially available (R 2-2-hydroxy-4-ethyl phenyl butyrate can be obtained as a white solid: melting point 1 7 6-1 7 7 ° C: [a] 25 / D = + 7.58 ° (10.692 mg / mL, CHC13); NMR (DMSO-d6); δ 13.0 (broad s, 1H, COOH), 8.21 (ddd , J = 8, 7, 1 Hz, 1H), 7.73 (s, 2H), 7.67 (ddd, J = 8, 7, 1 Hz, 1H), 7.52 (ddd, J = 8, 7, 1 Hz, 1H), 7.46 (m, 1H), 7.32-7.28 (m, 2H), 7.24-7.18 (m, 3H), 5.03 (t, J = 6 Hz, 1H), 2.95 (m, 1H), 2.72 (m, 1H), 2.44 (s, 3H), 2.28 (m, 2H), 1.61 (s, 3H); MS (+ FAB): [M +], 3 bromine isotope pattern, 700 (30%), 702 (100%), 704 (75%), 706 706 (40%); Anal. Calc, for C30H23Br3O3S: C, 51.23, H3.30, N 0.00. Found: C, 51.15, H, 3.13, N, 0.00. Example 32 — (E_) 2 "^, 6-Erchun-4-(9-? 赛-2. 3---dense ~ ~ Ji, Zhong__Bf __L2 _ * — 3—: b 1, -H channeling Pan-4-a)-Jujube, a 1-4-Judean tincture method of Example 3 0, from 2,6 _ dibromo-4-(9 -bromo-2, 3 -dimethyl-naphthalene 骈[2,3-b-blazepan-4 -yl) -phenol (Example 9) and (S)-2 -hydroxy-4 -phenylbutene-95- This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) ------------------- Order --------- (Please read the notes on the back first Refill this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7_ V. Description of the invention (94) Ethyl acetate (洌 27) can be made into a white solid: [a] 25 / D = -12.187 ° (9.929 mg / mL, CHC13); NMR (DMSO-d6); δ 13 · 24 (s, 1H), 8.21 (d, J = 8 Hz, 1H), 7.73 (s, 2Η), 7.67 (ddd, J = 8, 7, 1 Hz, 1H), 7.52-7.45 (m, 2H), 7.32-7.28 (mt 2H), 7.24-7.20 (m, 3H) 5.02 (d, J = 6Hz, 1H), 2.99-2.86 (m, 1H), 2.75-2.65 (m, 1H), 2.45 (s, 3H), 2.30-2.20 (m, 2H), 1.61 (s, 3H); MS (+ FAB): (M +), 3 bromine Isotope pattern 700 (30%), 702 (100%), 704 (90%), 706 (55%); Anal. Calc, for C30H23Br3O3S: C, 51.23, H, 3.30, N, 0.00. Found: C, 51.33 H, 3.33, N, 0.29. Example 33 —LJLI—J—Didibromo-4- (2, Nitta- 9-¾ 礒鶸 Mou-sai 骈 "2 * 3-b H 家盼 -4- A)-Rongxia a 1-3-moprofidine method Example 3 0, from 2, 6-dibromo-4-(2, 3-dimethyl-9-benzenesulfonyl-naphthalene fluorene [2 , 3-b Buphenphen-4 -yl) -phenol (Example 13) and (S) methyl 2-hydroxy-3-phenylpropanoate (Example 25) can be prepared as a white solid: opt. Rot. [ a) 25 / D = + 22.84 ° (1 0.068 mg / mL, CHC13); NMR (DMSO-d6); δ 13.13 (broad s, 1H), 8.42 (d, J = 8 Hz, 1H), 7.75 (t, J = 2 Hz, 2H), 7.58 ( ddd, J = 8, 7, 1 Hz, 1H), 7.50 (ddd, J = 8, 7, 1 Hz, 1H), 7.44 (d, J = 8 Hz, 1H), 7.37-7.19 (m, 7H) , 7.15-7.11 (m, 1H), 7.03-7.00 (m, 2H), 5.22 (t, J = 7 Hz, 1H), 3.37-3.28 (m, 2H), 2.39 (s, 3H), 1.62 (s , 3H); MS (El): [M +], 2 bromine isotope pattern, 716 (10%), 718 (20%), 720 (10%); Anal. Calc, for C35H26Br203S2: C, 58.50, H, 3.65 , N, 0.00. Found: C, 58.77, H, 3.94, N, 0.16. Example 34 __ ~ 2 「2 * 6 -Eichun-4-(2 * __ 3 ~ Dimethylbenzyl-Selenium」 2, 3-h Ί-嗦 -4-4-a)-ruthenium 1-propyl hydrazone Example 30 method, from 2, G-dibromo-4-(2, 3-dimethyl-9- Benzenesulfonyl-naphthalene [2 5 3 -b and Btpan-4 -yl] -phenol (Example 13) and commercially available (S)

-(-)-乳酸甲酯可製得白色固體：熔點2 3 7 - 2 3 9 °C : [ a ] 2 5 / D -90- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） -------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 51〇9〇〇 A7 〜_____B7 五、發明說明（K ) =-1.99° (10.051 mg / mLt CHC13); NMR (DMSO-d6); δ 13.2 (broad s, 1H, COOH), 8.43 (d, J = 8 Hz, 1H), 7.80 (s, 2H), 7.62-7.58 (m, 1H), 7.56-7.50 (m, 2H), 7.23-7.13 (m, 3H), 7.04-7.01 (m, 2H), 5.03 (quartet, J =7 Hz, 1H), 2.40 (s, 3H), 1.63 (s, 3H)，1.57 (d，J = 8 Hz, 3H); MS (El)·· [M+]，2 溴同位素式樣，640 (47%), 642 (100%), 644 (56%); Anal. calc, for C29H22Br203S2: C, 54.22, H, 3.45, N, 0.00. Found: C, 53.64, H, 3.33, N, 0.05. 例3 5 __________6 - 二 'M - 4 - ( 9 -淳 - 3 -甲基 - 2 - Q馬财-4 -甚申某-棠 ft—「2 * 3 - h 1-膝盼-4 -某）-茱氫某Ί - 3 -茱丙酴仿例3 0之方法，由2 , G -二溴-4 - ( 9 -溴-3 -甲基-2 -嗎 _木~ 4 ~基甲萘駢[2，3 - b ]-瞎吩〜4 -基）-鼢（例1 9 )及市售可得（S )-(-)-乳酸甲酯可製得黃色固體：〇pt.rot. [a] = -^26.512° ( Ifi . i 8 4 ra g / i L , D M S 0 ) ; N M R. (itfc - d 5 ) ; 8 . 4 1 (cl, J - 9 H z , 1 H } , 7 . 8 4 ( d d ? J = 3 . 1 Hz), ? * 7 0 ( d , J = 7 H z , 2 H )，7 e 4 3 - 7 ; 3 2 (爾，6 H ) 5 5 e 8 9 ( t.，J : 7 H z，1 H )，3 · 8 8 ( d q， 2 H ) , 3 . 7 7 ( t，J = 7 H z , 4 H )，3 · β 6 ( s , 2 H )，2 · 5 3 ( s，4 H )， 1 · 7 0 ( s，3 H ) ; M S ( + F A B ) : [ ( M + H ) + ]，3 溴同位素式樣， ? 7 2 ( 2 Q % )，7 7 4 ( 3 5 % ) , 7 7 6 ( 4 5 % ) ; H R M S，計算值： 7 7 1 · 9 3 6 7 4 C 3 3 Η 2 9 N 0 4 S B r 3 a s [ Μ + Η ];測定值：7 7 . 9 3 9 5 4 ，mass deviation 2 . 8 0 ro m u . anal . Calc, for C3 3H28Br3N04S: C, 5K18,H? 3 .649 N, 1.81.Found: C , 5 1 . 5 7，H，3 . 8 6，N，1 · 7 3 · 例36 2 - l~ 2- 二漳-4 - ( 9 -溴-3 -甲某-2 -礤咻-4 Ίφ 某一赛疆一―L.2__i__3: b 1 ~ 瞎盼- 4 -基)_-荣氣基"I -丙酸 -9 7 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂 --------線 41^ (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7____ 五、發明說明（％ ) 仿例3 0之方法，由2 , 6 -二溴-4 - ( 9 -溴-3 -甲基-2 -嗎啉-4 -基甲桊駢[2，3 - b卜瞎吩-4 -基）-酚（例1 9 )及（S卜2 -羥基-3 -苯丙酸甲酯（例2 5 )可製得黃色固體：[a ] 2 5 / D =+13.84° (10.043mg/mL，DMSO);NMR(Bft 啶-d5):3 8.42 (d, J = 8 Hz, 1H), 7.88 (s, 2H), 7.63 (m, 2H), 7.41 (m, 1H), 5.61 (q, J = 4 Hz, 1H), 3.78 (t, J = 4 Hz, 4H), 3.70-3.63 (m, 3H), 2.56 (s, 4H)t 1.97 (d, J = 7 Hz, 3H), 1.71 (s，3H); MS (+FAB): [(M+H)+]，3 溴同位素式樣，696 (35%)，698 (100%)， 700 (80%), 702 (40%); Anal. Calc, for C27H24Br3N04S*HCl: C, 44.14, H, 3.43, N, 1.91. Found: C, 44.94, H, 3.85, N, 1.83. 例37 (R) - 2 - f 2 · 6 -二》皇- 4 - ( 9 -溴-2 -二乙胺申某-3 -甲甚- 寮餅「2, 3 - bl -瞎盼-4-基）-篆氣基卜3~*荣丙酸仿例3 0之方法，由2，6 -二溴-4 - ( 9 -溴-2 -二乙胺甲基-3 -甲基-萘駢[2，3 _ b卜瞎吩-4 -基）-酚（例1 8 )及（S )-(-)-Methyl lactate can be obtained as a white solid: melting point 2 3 7-2 3 9 ° C: [a] 2 5 / D -90- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ------------------- Order --------- line (Please read the precautions on the back before filling this page) Wisdom of the Ministry of Economic Affairs Printed by the Consumer Affairs Cooperative of the Property Bureau 5109900A7 ~ _____ B7 V. Description of the invention (K) = -1.99 ° (10.051 mg / mLt CHC13); NMR (DMSO-d6); δ 13.2 (broad s, 1H, COOH ), 8.43 (d, J = 8 Hz, 1H), 7.80 (s, 2H), 7.62-7.58 (m, 1H), 7.56-7.50 (m, 2H), 7.23-7.13 (m, 3H), 7.04- 7.01 (m, 2H), 5.03 (quartet, J = 7 Hz, 1H), 2.40 (s, 3H), 1.63 (s, 3H), 1.57 (d, J = 8 Hz, 3H); MS (El) · · [M +], 2 bromine isotope pattern, 640 (47%), 642 (100%), 644 (56%); Anal. Calc, for C29H22Br203S2: C, 54.22, H, 3.45, N, 0.00. Found: C , 53.64, H, 3.33, N, 0.05. Example 3 5 __________ 6-Di'M-4-(9-Chun-3-Methyl-2-Q Ma Choi-4-Shen Shenmou-Tang ft-"2 * 3-h 1-Kipan-4-a)-Jujube a certain method-3-Juprobladder Example 30 method, from 2, G-Dibromo-4-(9 -Bromo-3 -Methyl-2-? _ Wood ~ 4 ~ Methylnaphthalene fluorene [2,3-b] -benzophene ~ 4 -yl) -fluorene (Example 1 9) and commercially available (S)-(-) -Methyl lactate can be prepared as a yellow solid: 〇pt.rot. [A] =-^ 26.512 ° (Ifi. I 8 4 ra g / i L, DMS 0); NM R. (itfc-d 5); 8 4 1 (cl, J-9 H z, 1 H), 7. 8 4 (dd? J = 3.1 Hz),? * 7 0 (d, J = 7 H z, 2 H), 7 e 4 3-7; 3 2 (E, 6 H) 5 5 e 8 9 (t., J: 7 H z, 1 H), 3 · 8 8 (dq, 2 H), 3. 7 7 (t, J = 7 H z, 4 H), 3 · β 6 (s, 2 H), 2 · 5 3 (s, 4 H), 1 · 7 0 (s, 3 H); MS (+ FAB): [ (M + H) +], 3 bromine isotope pattern,? 7 2 (2 Q%), 7 7 4 (3 5%), 7 7 6 (4 5%); HRMS, calculated value: 7 7 1 · 9 3 6 7 4 C 3 3 Η 2 9 N 0 4 SB r 3 as [Μ + Η]; measured value: 7 7. 9 3 9 5 4, mass deviation 2. 8 0 ro mu. Anal. Calc, for C3 3H28Br3N04S: C, 5K18, H? 3 .649 N, 1.81.Found: C, 5 1. 5 7, H, 3. 8 6, N, 1 · 7 3 · Example 36 2-l ~ 2- Erzhang- 4-(9 -bromo-3 -a certain -2-礤咻 -4 Ίφ a certain match Ⅰ-L.2__i__3: b 1 ~ blind hope-4 -based) _-Rongqi based " I -propionic acid-9 7-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ------- ------------- Order -------- Line 41 ^ (Please read the notes on the back before filling out this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7____ V. Description of the invention (%) The method of Example 30 is based on 2, 6-dibromo-4-(9 -bromo-3 -methyl-2 -morpholine-4 -ylformamidine [2,3 -b-Buphen-4 -yl) -phenol (Example 19) and (S-Bu 2-hydroxy-3 -phenylpropionate methyl ester (Example 25)) can be prepared as a yellow solid: [a] 2 5 / D = + 13.84 ° (10.043mg / mL, DMSO); NMR (Bft pyridine-d5): 3 8.42 (d, J = 8 Hz, 1H), 7.88 (s, 2H), 7.63 (m, 2H), 7.41 ( m, 1H), 5.61 (q, J = 4 Hz, 1H), 3.78 (t, J = 4 Hz, 4H), 3.70-3.63 (m, 3H), 2.56 (s, 4H) t 1.97 (d, J = 7 Hz, 3H), 1.71 (s, 3H); MS (+ FAB): [(M + H) +], 3 bromine isotope pattern, 696 (35%), 698 (100%), 700 (80% ), 702 (40%); Anal. Calc, for C27H24Br3N04S * HCl: C, 44.14, H, 3.43, N, 1.91. Found: C, 44.94, H, 3.85, N, 1.83. Example 37 (R)-2 -f 2 · 6-2 "Emperor-4- (9 -bromo-2 -diethylamine Shenmou -3 -methyl--glutamate cake "2, 3-bl -blazepan-4-yl)-hydrazine 3 ~ Method by using 2,6-dibromo-4-(9 -bromo-2 -diethylaminemethyl-3 -methyl-naphthalenepyrene [2,3 _ bbuphen-4 -yl) -phenol (example 1 8) and (S)

- 2 -羥基-3 -苯丙酸甲酯（例2 5 )可製得白色固體：N M R (D M S 0 - d 6 ) : 0' 1 3 . 3 ( b r o a d b a η d , 1 Η ) , 8 . 2 0 ( d , J = 8 Η ζ , 1 Η ) 7.70(s, 2Η), 7·66 (ddd，J = 8, 7, 1 Ηζ，1Η)，7.51(ddd，J = 8, 7, 1 Hz, 1Η)，7·40 · 7.25(m, 6Η), 5.21(t, J = 7 Hz, 1H), 3.75(s, 2H), 3.32(dd, J = 4, 3 Hz, 2H), 2.55 (q, J = 7 Hz, 4H), 1.63(s, 3H), 1.02 (t, J = 7 Hz, 6H) MS [(+)FAB]: [M + H]+ @ m/z 7 5 8，3 溴同位素式樣，7 5 8 ( 2 5 % )，7 6 0 ( 8 0 % )，7 6 2 ( 7 5 % ) ，7 6 4 ( 3 5 %) , 6 8 9 ( 1 0 0 %) ; Anal HPLC，Primesphere 5C~ 1 8柱，6 2 %乙晴1 5分顯示9 7 · 8 %純度；高解離M A ( F A B ) + ve:計算值：759.9556 for C33H31N03Br3 as [M+H]， t_l!定值.7 5 9 . 9 7 3 7 0 mass deviation: 18. 17 nnn . 例38 -98- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7_ 五、發明說明（W ) ，可製得標題化合_之黃色固體（1.7克，2?%):^{^(1)^!30- d6): δ 9.49 (s, 1H), 8.42 (s, 1H), 7.94 (d, 1H), 7.47-7.32 (m, 3H), 7.01 (s, 1H), 6.93 (s，2H), 3.32 (m，1H)，2.39 (s，3H)，1.59 (s，3H)，1·19 (d，6H). 驟2 乙酴2 -里而甚- 4- - ( …：^二牢某-棻駢Γ 2、3 - b 1 -瞟盼- 4 - ― 基丄二ill一_ 仿例49步驟3之方法，由2 -異丙基-4- (2，3 -二甲基- 蕃驗[2，3 - h ]-瞎盼~ 4 -基）-® ( Π · 5克，1 · 4毫吴耳），乙酔 (0」7毫升，1 . 8毫莫耳），及吡啶（3 · 5毫升）可製得標題化-2 -Hydroxy-3 -phenylphenylpropionate (Example 25) can be obtained as a white solid: NMR (DMS 0-d 6): 0 '1 3. 3 (broadba η d, 1 Η), 8.2 0 (d, J = 8 Η ζ, 1 Η) 7.70 (s, 2Η), 7.66 (ddd, J = 8, 7, 1 Ηζ, 1Η), 7.51 (ddd, J = 8, 7, 1 Hz , 1Η), 7.40 · 7.25 (m, 6Η), 5.21 (t, J = 7 Hz, 1H), 3.75 (s, 2H), 3.32 (dd, J = 4, 3 Hz, 2H), 2.55 ( q, J = 7 Hz, 4H), 1.63 (s, 3H), 1.02 (t, J = 7 Hz, 6H) MS [(+) FAB]: [M + H] + @ m / z 7 5 8, 3 Bromine isotope pattern, 7 5 8 (2 5%), 7 6 0 (8 0%), 7 6 2 (7 5%), 7 6 4 (3 5%), 6 8 9 (1 0 0%) ; Anal HPLC, Primesphere 5C ~ 18 column, 62% acetic acid 15 points showing 9 7 · 8% purity; high dissociation MA (FAB) + ve: calculated value: 759.9556 for C33H31N03Br3 as [M + H], t_l ! 5. 9 5 9. 9 7 3 7 0 mass deviation: 18. 17 nnn. Example 38 -98- This paper size applies the Chinese National Standard (CNS) A4 (210 X 297 mm) ----- --------------- Order --------- line (Please read the precautions on the back before filling out this page) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A 7 B7_ V. Description of the invention (W), a yellow solid (1.7 g, 2?%) Of the title compound can be prepared: ^ {^ (1) ^! 30-d6): δ 9.49 (s, 1H), 8.42 (s, 1H), 7.94 (d, 1H), 7.47-7.32 (m, 3H), 7.01 (s, 1H), 6.93 (s, 2H), 3.32 (m, 1H), 2.39 (s, 3H), 1.59 (s, 3H), 1.19 (d, 6H). Step 2 酴酴 2 -Li even-4--(…: ^ Ⅱ Er Mou-棻骈 Γ 2, 3-b 1-瞟望- 4-― 丄 ill ill a _ The method of step 3 of Example 49 is based on 2-isopropyl-4- (2,3 -dimethyl-fan test [2,3-h] -blaze ~ 4- Based) -® (Π · 5g, 1.4 milliwatts), acetamidine (0 "7ml, 1.8mmol), and pyridine (3.5ml) to make the title

合物之白色固體（0.48 克，8G%): NMR (DMSO-d6): δ 8.49 (s，1H)，8J 7.96 (d, 1H), 7.48-7.31 (m, 4H), 7.20 (s, 2H), 3.10 (septet, 1H), 2.40 (s, 3H), 2.37 (s, 3H), 1.56 (s, 3H), 1.16 (d, 6H). 步驟3 乙酸2 -異丙某- 4 -（ 9 -淳-2 二二―里„基二蓋_盤_ J 2」3 - b 1 - 蹲盼- 4 -某}-篆？彷例49步驟4之方法，由乙酸2-異丙基-4- (2, 3-二甲基-萘駢[2，3-b] - H寒盼-4-基）-苯酯（0.38克，0.37 毫莫耳），氯化鐵（8毫克，Q.51毫莫耳），溴（〇β055 毫升9 1 β 1毫莫耳），及二氯甲烷（5毫升）可製得標題化合物之白色固體（0 . 4 0克，8 8 % ) : ( D M S 0 - d 6 ) : <5 8 β 2 0 (d , 1 Η ) , 7 . 6 7 - 7 . 6 2 (1 , 1 Η ) , 7 . 5 2 - 7 . 4 3 (1 , 2 Η } , 7 . 3 4 ( d , 1 Η ) ? 7 . 2 2 (ι 5 2 Η ) , 3 e 0 9 ( s e ρ t e t , 1 Η ) , 2 . 4 3 ( s 5 3 Η } ? 2 . 3 7 ( s , 3 Η )White solid (0.48 g, 8G%): NMR (DMSO-d6): δ 8.49 (s, 1H), 8J 7.96 (d, 1H), 7.48-7.31 (m, 4H), 7.20 (s, 2H ), 3.10 (septet, 1H), 2.40 (s, 3H), 2.37 (s, 3H), 1.56 (s, 3H), 1.16 (d, 6H). Step 3 Acetic acid 2-isopropyl-4-(9 -Chun-2 22-Li ― Ji Er Gai_Pan_ J 2 ″ 3-b 1-Squat Pan-4-Some}-篆? The method of step 4 of Example 49 was followed by acetic acid 2-isopropyl-4 -(2,3-dimethyl-naphthalenepyrene [2,3-b] -H-Hanpan-4-yl) -phenyl ester (0.38 g, 0.37 mmol), ferric chloride (8 mg, Q. 51 mmol), bromine (0β055 ml 9 1 β 1 mmol), and dichloromethane (5 ml) to obtain the title compound as a white solid (0.40 g, 88%): (DMS 0-d 6): < 5 8 β 2 0 (d, 1 Η), 7.6 7-7. 6 2 (1, 1 Η), 7. 5 2-7.. 4 3 (1, 2 Η }, 7. 3 4 (d, 1 Η)? 7. 2 2 (ι 5 2 Η), 3 e 0 9 (se ρ tet, 1 Η), 2. 4 3 (s 5 3 Η)? 2. 3 7 (s, 3 Η)

5 4 ( s , 3 Η ) J · 1 6 和 1. β 1 5 (二雙線，6 Η ,旋轉異構物）；μ S U ΐ ) : [ Μ + ]，1 溴同位素式樣，4 6 G / 4 6 8 , Α τι a 1 . C a 1 c . - 1 ο ο - 本紙張尺度適用中國國家標準（CNS)A4規格（210 x 297公釐） ' · ' -- -------------------訂--------- (請先閱讀背面之注意事項再填寫本頁) 510900 A7 B7_ 五、發明說明（W )5 4 (s, 3 Η) J · 1 6 and 1. β 1 5 (two double lines, 6 Η, rotamers); μ SU ΐ): [Μ +], 1 bromine isotope pattern, 4 6 G / 4 6 8, Α τι a 1. C a 1 c.-1 ο ο-This paper size applies to China National Standard (CNS) A4 (210 x 297 mm) '·'------- ------------- Order --------- (Please read the notes on the back before filling this page) 510900 A7 B7_ V. Description of the invention (W)

I for C25H23Br02S : C, G 4, 2 4 , H?[9G, N.O.OQ.found: (請先閱讀背面之注意事項再填寫本頁) C , fi 3 . 8 4 , ΪΙ , 4 „ 9 0 , N , 0 . 0 G 〇步驟4 2 -異丙某- 4 -（ 9 -淳- 2 · 3 -二 _ 某-養「2 * 3 - b 1 -陳盼 - 4-某）-· 仿例4 9步驟5之方法，由乙酸2 -異丙基-4 - ( 9 -溴~ 2， 3 -二甲基-萘_ [ 2， 3 _ b ] ~瞎盼-4 _基）-苯酷（0 · 3 9克，〇.83毫莫耳），！[{)則容液（1»0毫升之]^溶液，1.0毫莫耳四氫呋喃（1 4毫升），及甲醇（8 · 5毫升）可製得標題化合物之乳色固體（Q · 3 5 克，9 9 % ) : ( D M S 0 - d 6 ) : 3 9 · 5 6 (s， 1H), 8.17 (d, 1H), 7.64-7.60 (ddd, 1H), 7.53-7.52 (d, 1H), 7.46-7.42 (ddd, 1H), 7Ό3 (d,lH), 6.97-6.91 (m, 2H), 3.31-3.28 (m,lH), 2.42 (s, 3H), 1.58 (s, 3H), 1.16 (d, 6H); MS(EI): [M+]，1 溴同位素式樣，424/426; Anal· Calc, for C23H21BrOS: C, 64.94, H, 4.98, N, 0.00. Found: C, 64.11, H, 4.99, N, 0.03. 步驟5 2 -溴-4 - ( 9 -湟- 2 , 3 -二 _ 某-棻酣「2 * 3 ~ h 1 - I?索盼- 4 -某）二 6 二_M_.•西— 經濟部智慧財產局員工消費合作社印製於含2 -異丙基~ 4 - ( 9 -溴-2，3 -二甲基-萘駢[2，3 - b ] -瞎盼-4 -基）-酚（(K 3 5克，0 · 8 1毫莫耳）及乙酸鉀（0 · 8 0 克，8 . 1 1毫莫耳）之冰醋酸（1 1毫升），於室溫下滴加入含溴（f) » 〇 5毫升，11 · 9 7毫莫耳）之冰醋酸（1 · 5 0毫升）。於室溫下攬拌4小時後以少量稀釋亞硫酸氫鈉溶液中止反應，稀釋以水（]〇〇毫升）。以玻璃漏斗收集固體，水洗並乾燥（Nat2 C0 4 )可得檫題化合物之白色固體（0.4克 -1 0 1 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） )川9〇〇 A7 __B7___ 五、發明說明（、# ) 9 98%):熔點 15卜 16 2°C : (DMSO-d6): δ9·20 (s，1H)，8·19 (d， (請先閱讀背面之注意事項再填寫本頁) 出)，7.66-7.61 (m，1H)，7.49-7.48 (m，2H)，7.35 (d，1H)，7.13 (d，lH)，3.40 (septet，出)，2.42 (s，3H), 1.60 (s，3H), U6 (d，6H); MS(+FAB): [M+H]，2 溴同位素式樣，502 (12%)，504 (30%)，506 (18%);八1^1.€&1(：.如€23扣03^〇5: c，54.78, Η, 4.00, N，0.00· Found: C，53·67, Η, 3.84, N，0·03· 例4 0 A 二2丄2二溴-4·-（ 9-'海-2 · 3-二甲基-養 if「2丄—1 二IlL·:— ί1室—盼-4 -華）-6 -黑丙荣氤基1 - 3 ~ 步驟 1 Q g、- ?「2 -漳-4 - ( 9 -漳-2 · 3 - 二甲基二 -a索盼-4 -甚> -6 -黑丙茱氫某1 - 3 -笨丙mi„ 仿例4 9步驟6之方法，由2 -溴-4 - ( 9 -溴-2，3 -二甲基 -萘駢[2，3 - b卜瞎吩-4 -基）-6 -異丙酚（0 · 3 6克，0 · 7 2 毫莫耳），（S) -2-羥基-3_苯丙酸甲酯（〇 · 19克，1 · 1 毫莫耳），三苯瞵（0 · 2 8克，1 · 1毫莫耳），偶氮二羧酸二乙酯（0.17毫升，毫莫耳）及無水苯（：4·0毫升），於油浴（8(TC ) 4 · 5小時可製得標題化合物之白色固體（0 , 2 7 克，5 6 % ) : ( D M S 0 - d 6 ) : 8 · 2 0 ( d，1 Η )，7 · 7 0 經濟部智慧財產局員工消費合作社印製 ~7.60(i,1H) ,7.6 0~7.40(m,2H) ,7.40-7.20(ffl,7ffi) ,5.07 和4 · 9 5 (二三線，1 Η，旋轉異構物），3 · 6 0和3 · 5 6 (二 s， 3 Η，旋轉異構物），3 . 4 0 - 3 · 2 0 ( m，3 Η )，2 · 4 5 和 2 · 4 3 (二單線，3 Η，旋轉異構物），1 · 5 9和1 · 5 3 (二單線，3 Η，旋轉異構物），1 · 2 0 - 1 · 0 0 ( m，6 Η )。步驟 2 ( 2 R) - 2「2 -漳-4 - ( Q -海-2 · 3 -二申基-養..盟„ 「2, 睛盼-4-甚）-6 -異苯氧基卜3二苯一S·-避- -102- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印製 510900 Α7 ______Β7_ 五、發明說明) 仿例4 9步驟7之方法，由（2 R ) - 2 [ 2 -溴-4 - ( 9 -溴-2， 3 -二甲基-蔡駢[2，3 - b ]-瞎盼-4 -基）-6 -異丙苯氣基] -3-苯丙酸甲酯（〇·26克，0·52毫莫耳），Κ0Η溶液（1.1 毫升之1Ν溶液，1.1毫莫耳），四氫呋喃（6毫升），及甲醇（2毫升）可製得標題化合物之白色固體（0 · 2 3克， 6 8 % ) : OPT . Ro t . [ a ] 25/D=+38.90 (9.97〇Big/fflL， CHC13); (DMS0-d6): 313.1(寬 s，lH)， 8.19(d，lH), 8.19(d,lH),7.68-7.62(in,lH), 7.53-7.44(m,2H)> 7.40-7.38(πι,1Η), 7.35-7.30(ai,4H), 7.29-7.23(m, 2H)，5.0fl(wi，lH)，3.55(septet，lH)，3.35(m，2H)，2.42 和 2 · 4 3 (二單線，3 H，旋轉異構物），1 · 5 7和1 · 5 2 (二單線，3H，旋轉異構物），1·14-1·03(ιη,6Η); MS( + FAB): [M+] ，2 溴同位素式樣，650(15%), 652(30%)， 654(21%);I for C25H23Br02S: C, G 4, 2 4, H? [9G, NOOQ.found: (Please read the precautions on the back before filling out this page) C, fi 3. 8 4, ΪΙ, 4 „9 0, N, 0. 0 G 〇 Step 4 2-Isopropyl-4-(9-Chun-2 · 3-Two _--raise "2 * 3-b 1-Chen Pan-4--)-Example 4 9 The method of step 5 consists of 2-isopropyl-4-(9 -bromo ~ 2, 3-dimethyl-naphthalene _ [2, 3 _ b] ~ blind-4 _yl) -benzene (0.39 g, 0.83 mmol), [{) is a solution in liquid (1 »0 ml of ^^ solution, 1.0 mmol of tetrahydrofuran (14 ml), and methanol (8.5 ml ) A cream-colored solid (Q · 35 g, 99%) of the title compound was obtained: (DMS 0-d 6): 3 9 · 5 6 (s, 1H), 8.17 (d, 1H), 7.64- 7.60 (ddd, 1H), 7.53-7.52 (d, 1H), 7.46-7.42 (ddd, 1H), 7Ό3 (d, lH), 6.97-6.91 (m, 2H), 3.31-3.28 (m, lH), 2.42 (s, 3H), 1.58 (s, 3H), 1.16 (d, 6H); MS (EI): [M +], 1 bromine isotope pattern, 424/426; Anal · Calc, for C23H21BrOS: C, 64.94, H, 4.98, N, 0.00. Found: C, 64.11, H, 4.99, N, 0.03. Step 5 2 -bromo-4-(9-湟-2, 3 -di_ 棻酣-棻酣2 * 3 ~ h 1-I? Sopan-4-a) 2 6 2 _M_. • West — The Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs is printed on containing 2 -isopropyl ~ 4-(9 -bromo- 2,3 -Dimethyl-naphthalenepyrene [2,3-b] -Banpan-4 -yl) -phenol ((K 3 5 g, 0.81 mmol) and potassium acetate (0 · 8 0 G, 8.11 mmoles of glacial acetic acid (11 ml), dropwise add bromine (f) »0.05 ml, 11.97 mmoles of glacial acetic acid (1.5 ml at room temperature) 0 ml). After stirring at room temperature for 4 hours, the reaction was stopped with a small amount of diluted sodium bisulfite solution, diluted with water (100 ml). The solid was collected in a glass funnel, washed with water and dried (Nat2 C0 4) to obtain White solid of the title compound (0.4 g-1 0 1-This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 mm)) Chuan 900A7 __B7___ V. Description of the invention (, #) 9 98 %): Melting point 15b 16 2 ° C: (DMSO-d6): δ9 · 20 (s, 1H), 8 · 19 (d, (Please read the precautions on the back before filling this page) Out), 7.66- 7.61 (m, 1H), 7.49-7.48 (m, 2H), 7.35 (d, 1H), 7.13 (d, 1H), 3.40 (septet, ), 2.42 (s, 3H), 1.60 (s, 3H), U6 (d, 6H); MS (+ FAB): [M + H], 2 bromine isotope pattern, 502 (12%), 504 (30% ), 506 (18%); eight 1 ^ 1. € & 1 (: such as € 23 deduction 03 ^ 〇5: c, 54.78, Η, 4.00, N, 0.00 · Found: C, 53 · 67, Η , 3.84, N, 0 · 03 · Example 4 0 A bis 2 丄 2 dibromo-4 ·-(9-'sea-2 · 3-dimethyl-trophic if 2 丄 -1 di IlL ·: — ί1 Chamber—Pan-4 -Hua) -6-Hei Bingrongyi 1-3 ~ Step 1 Q g,-? 2 -Zhang-4-(9 -Zhang-2 · 3-dimethylbis-a Pan-4-even > -6-Hemipropane hydrochloride 1-3-Benzene mi mi Example 4 9 Step 6 method, from 2-bromo-4-(9 -bromo-2,3 -dimethyl -Naphthyl naphthalene [2,3 -b-buphenphen-4 -yl] -6 -propofol (0.36 g, 0.72 mmol), (S) -2-hydroxy-3_ Methyl phenylpropionate (0.19 g, 1.1 mmol), triphenylhydrazone (0.28 g, 1.1 mmol), diethyl azodicarboxylate (0.17 mL, mmol Moore) and anhydrous benzene (: 4.0 ml) in an oil bath (8 (TC) 4 · 5 hours to obtain the title compound as a white solid (0, 27 g, 56%): (DMS 0- d 6): 8 · 2 0 (d ， 1 Η ), 7.70 printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs ~ 7.60 (i, 1H), 7.60 ~ 7.40 (m, 2H), 7.40-7.20 (ffl, 7ffi), 5.07 and 4 · 9 5 ( Second and third lines, 1 Η, rotomer), 3 · 60 and 3 · 5 6 (two s, 3 Η, rotomer), 3. 40-3 · 2 0 (m, 3 Η), 2 · 4 5 and 2 · 4 3 (two single lines, 3 Η, rotomers), 1 · 5 9 and 1 · 5 3 (two single lines, 3 Η, rotomers), 1 · 2 0-1 0 0 (m, 6 Η). Step 2 (2 R)-2 "2 -Zhang-4-(Q -Hai-2 · 3 -Dishenyl-Yangan .." "2, Jipan-4-even) -6 -isophenoxy Bu 3 Diphenyl-S · -Avoid--102- This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) Printed by the Employees' Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 Α7 ______ Β7_ 5. Description of the invention Example 4 9 The method of step 7 is based on (2 R)-2 [2 -bromo-4-(9 -bromo-2, 3 -dimethyl-Ceamidine [2,3-b] -blaze-4 -Yl) -6-cumene carbamoyl] -3-phenylpropanoate (0.26 g, 0.52 mmol), K0Η solution (1.1 ml of 1N solution, 1.1 mmol), tetrahydrofuran (6 ml) and methanol (2 ml) to obtain the title compound as a white solid (0.23 g, 68%): OPT. Ro t. [A] 25 / D = + 38.90 (9.97〇Big / fflL, CHC13); (DMS0-d6): 313.1 (width s, lH), 8.19 (d, lH), 8.19 (d, lH), 7.68-7.62 (in, lH), 7.53-7.44 (m, 2H) > 7.40-7.38 (π, 1Η), 7.35-7.30 (ai, 4H), 7.29-7.23 (m, 2H), 5.0fl (wi, lH), 3.55 (septet, lH), 3.35 (m, 2H) , 2.42 and 2. 4 3 (two single wires, 3 H, rotamer), 1 · 5 7 and 1 · 5 2 (two single wires, 3H, rotamer), 1.14-1 · 03 (ιη, 6Η); MS (+ FAB): [M +], 2 bromine isotope pattern, 650 ( 15%), 652 (30%), 654 (21%);

Anal. Calc, for C32H28Br203S: C, 58.91, H, 4.33, N，0.00. Found : C，58.72，H , 4 . 4 5, N,0. 10 〇例41 - 2 - U - ( 2 . 3 -二申基-養駢 f 2 . 3 - b 1 -睹盼 -2 -羅W茱氩某1-3-茱而酴步驟 1 ( R ) - 2 U - ( 2 . 3 -二申某-棻「2 . 3 - b 1 -嗦甚）-2 -異丙茱氫某1-3-茏丙酴田酷仿例4 9步驟6之方法，由4 - ( 2，3 -二甲基-綦駢[2，3 - b ] -睹盼-4-基）-2-異丙酚（0 · 30克，0 · 87毫莫耳），（S) -2 -羥基-3-苯丙酸甲酯（0·62克，3·5毫莫耳），三苯瞵（0.91克，3.5毫莫耳），偶氮二羧酸二乙酯（0.54毫 -1 0 3 - 本紙張尺度適用中國國家標準（cns)a4規格（210 χ 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 510900 A7 _B7_ 五、發明說明（、a) 升，3.5毫莫耳）及無水苯（7.(]毫升），於油浴（85£€) 18小時可製得標題化合物之黃色油（0.18克，4 1%): (DM SO-dC ) : (5 8,4fl(s，lH)，7.90(d，lH)，7·50-7·20(ηι， GH ) , 7 . 20~7 . 00 (ι , 3Η) , 7.00~6.80(ηι52Η), 5 . 2 0 (t , 1 Η ) ，3.65和3.63(二8,311，旋轉異構物），3.3 0- 3.2()(1»，31〇 ,2 · 4 0 (s，3 Η )，1 » 5 0 ( s，3 Η ) , 1 · 1 5 (二雙線，3 Η，旋轉異構物），1 · 0 5 (二雙線，3 Η，旋轉異構物）。步驟2 ( R ) - 2 f 4 - ( 2 . 3 -二申某-若駢「2 , 3 - b 1-睐盼 - 4-某）- 2-¾丙荣氩某Ί -3-茏丙· 仿例4 9步驟7之方法，由（R) - 2 [ 4 - ( 2，3 -二甲基-禁駢[2，3-b卜瞎盼-4-基）-2 -異丙苯氣基卜3 -苯丙酸甲酯（〇·18克，（K35毫莫耳），Κ0Η溶液（0·71毫升之1N 溶液，〇·71毫莫耳），四氫呋喃（6毫升），及甲醇（2 毫升）可製得標題化合物之白色固體（0.072克，41%): :(DMS0-d6) : <5 13.10(寬 S，1H}，8 . 4 3 ( d , 1 Η ) , 7.49 (dd，lH)， 7.46-7.29(m,7H), 7 . 2 8 - 7 . 2 2 ( ra , 1H) ,7. 10 - (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製例 9 和線； 8 8 4 . 3 雙 9 6 · - 4 2 二 _— 線單物構異轉旋物構異轉旋 Μ 駢赛 - 某甲二本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 B7_ 五、發明說明（、A) -睹盼-4 -某）-6 -镔二丁茱氬某Ί - 3-茱丙酴步驟1 2 -箆二丁某-4-(2> 3 -二甲某-若駢F2. 3-bl -睹 (請先閱讀背面之注意事項再填寫本頁) 盼-4-某）-酚仿例49步驟1之方法，由3-第二丁基-對大舗香醇酸 (3.0克，14.4毫莫耳，依 M.Derenberg及 P.Hodge， Tetrahedron Lett. 1971， 3825~3828:D.G. Davies 等人，J· Chem· Soc· ( C) 1971, 455-460)，草醯氯（1·4毫升，15·8毫莫耳），N，N-二甲基甲醱胺（2滴），2 , 3 -二甲基-5 -苄基瞎吩（3 · 5克，1 6 · 6毫莫耳），氯化錫（IV) ( 1.5毫升，15.8毫莫耳），及無水二氯甲烷 (9 2毫升），可製得油（6 · 2克），其可不經純化直接使用。仿例4 9步驟1之方法，由（2 -苄基-4，5 -二甲基-_盼 - 3 -基）-(3 -第二丁基-4 -甲氯苯基）-甲酮（6 · 2克， 15· 8毫莫耳），三溴化硼（7.1毫升，7 4. 8毫莫耳），及二氯甲烷（5 4毫升），可製得標題化合物之固體（2 · 3 4 克，4 1%) : M S ( E I ) : [ H + ] 3 6 0 〇步驟 2 2 -淳-4- (9 -淳-2. 3-二申某-赛駢 f2. 3-b1-_ 盼-4 -某）- β -第二丁某酚經濟部智慧財產局員工消費合作社印製仿例3 9步驟6之方法，由2 -第二丁基-4 - ( 2，3 -二甲基-葉駢[2，3- b】-睹盼-4-基 >-勸（2.34克，6.5毫莫耳），溴（〇·69毫升，13毫莫耳），乙酸鉀（6.4克， 65毫莫耳），及冰醋酸（65毫升）可製得檫題化合物之固體（〇 · 6 3克，1 9 % ) : M S ( Ε I ) : [ Μ + ] , 2溴同位素 -1 0 5 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印製 510900 Α7 Β7 五、發明說明（、吟）式樣，516(50%)， 518(100%)， 520(55%)。步驟 3 ( R) - 2 - Γ 2 -溴-4 -(卜湟-2 · 3 - U 基-藶1- ί 2 > 3-1)1-瞎盼-4_某）-6~第一> 丁基—一3 二.—本― 丙酴仿例49步驟6之方法，由2-溴-4- ( 9-溴'2，3-二甲基 -萘駢[2，3-b卜瞎盼-4-基）-6-第二丁基酚（0.63克， 1.2毫莫耳），（s) -2-羥基-3-苯丙酸甲酯（0 · 44克， 2.4毫莫耳），三苯瞵（0.64克，2.4毫莫耳），偶氮二羧酸二乙酯（0,38克，2·4毫莫耳）及無水苯（2.4毫升），於室溫下反應5天可製得油（0.60克，72%),其可不經純化直接使用。仿例49步驟7之方法，由（R> -2 [ 2-溴-4- ( 9-溴-2 , 3-二甲基-萘駢[2，3-b]-瞎盼-4-基）-6-第二丁基苯氣基卜3-苯丙酸甲酯（0.55克，0.73毫莫耳），KOH溶液 (1·6毫升之1N溶液，1.6毫莫耳），四氫呋喃（7.5毫升），及甲醇（2·5毫升）可製得標題化合物之泡沫 (0.26 克，48%) : MS(EI): [Μ+]，2 溴同位素式樣， 6 6 4 ( 1 4 % ) , 6 6 6 ( 2 6 % ) , 668(14%); Anal . Calc - for C33H30Br 203S: C,59.47，H，4.54，N，0·00· Found: C,59.44, Η，4·81, N , 0 . 03〇例43 (R ) - 2 -「2 -海-4- ( 9 -漳-2 . 3二二甲基二胤『2 , 3 - b 1 -_盼-4 -某）--乙荣氩甚1 - 3 -茉嚴-酸— 步驟1 ( 2-辛某-4 · 5-二田崠盼-3-基）-—(3-乙某讎4- -108- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） -------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) A7Anal. Calc, for C32H28Br203S: C, 58.91, H, 4.33, N, 0.00. Found: C, 58.72, H, 4. 4 5, N, 0. 10 〇 Example 41-2-U-(2. 3- Ershenji-raises f 2. 3-b 1-Kanpan-2-Luo W Zhu Ar 1-3-Zhu and Er step 1 (R)-2 U-(2.3-Ershen-棻"2.3-b 1-嗦)-2-isopropylhydrogen 1-3-propyl acetone Putian Cool Example 4 9 Step 6 method, from 4-(2, 3-dimethyl-fluorene骈 [2,3-b] -Mepan-4-yl) -2-propofol (0. 30 g, 0. 87 mmol), (S)-2-Hydroxy-3-phenylpropionate Esters (0.62 g, 3.5 mmol), Triphenylhydrazone (0.91 g, 3.5 mmol), Diethyl azodicarboxylate (0.54 mmol-1 0 3-This paper is for Chinese countries Standard (cns) a4 specifications (210 x 297 mm) -------------------- Order --------- line (please read the first Note: Please fill in this page again) 510900 A7 _B7_ 5. Description of the invention (, a) liter, 3.5 mmol) and anhydrous benzene (7. (] ml), the title can be obtained in an oil bath (85 £ €) for 18 hours Yellow oil of the compound (0.18 g, 41%): (DM SO-dC): (5 8,4fl (s, lH), 7.90 (d, lH), 7.50-7 · 20 (ηι, GH), 7.20 ~ 7.00 (ι, 3Η), 7.00 ~ 6.80 (ηι52Η), 5.20 (t, 1Η), 3.65 and 3.63 (two 8,311, rotational isomers) , 3.3 0- 3.2 () (1 », 31〇, 2 · 4 0 (s, 3 Η), 1» 5 0 (s, 3 Η), 1 · 1 5 (two double lines, 3 Η, rotation difference Structure), 1.05 (two double lines, 3 amidines, rotamers). Step 2 (R)-2 f 4-(2.3-Ershenmou-Ruo, "2, 3-b 1 -Lanpan- 4-a)-2-¾Bron argon a certain Ί -3- 茏 propyl · Example 4 9 Step 7 method, from (R)-2 [4-(2, 3-dimethyl- Confinement [2,3-b bublend-4-yl) -2 -cumene carbamoyl 3-phenylpropionate (0.18 g, (K35 mmol), K0Η solution (0 · 71 ml of a 1N solution, 0.71 mmol), tetrahydrofuran (6 ml), and methanol (2 ml) gave the title compound as a white solid (0.072 g, 41%):: (DMS0-d6): < 5 13.10 (width S, 1H), 8. 4 3 (d, 1 Η), 7.49 (dd, 1H), 7.46-7.29 (m, 7H), 7. 2 8-7. 2 2 (ra, 1H ), 7. 10-(Please read the precautions on the back before filling out this page) Employees' Intellectual Property Bureau, Ministry of Economic Affairs, Consumer Cooperation Printing example 9 and line; 8 8 4. 3 double 9 6 ·-4 2 2 _ — line single structure conformation rotation rotation structure conformation rotation rotation 骈骈-a paper size of a second paper is applicable to Chinese national standards (CNS ) A4 specification (210 X 297 mm) 510900 A7 B7_ V. Description of the invention (, A)-Jianpan-4-a) -6-Diethyl ruthenium argon-3-Ju Zhu 酴 Step 1 2-箆Dibutyl molybdenum-4- (2 > 3-Dimethyl molybdenum-Rhodium F2. 3-bl-See (please read the precautions on the back before filling this page) Pan-4-some)-Phenol Example 49 Step 1 The method is based on 3-second butyl-p-dipanolic acid (3.0 g, 14.4 mmol, according to M. Derenberg and P. Hodge, Tetrahedron Lett. 1971, 3825-3828: DG Davies et al., J. Chem · Soc · (C) 1971, 455-460), chloramphenicol (1.4 ml, 15.8 mmol), N, N-dimethylformamide (2 drops), 2, 3- Dimethyl-5 -benzylbenzophene (3.5 g, 16.6 mmol), tin (IV) chloride (1.5 ml, 15.8 mmol), and anhydrous dichloromethane (92 ml) ) To obtain an oil (6.2 g), which can be used without purification. Example 4 9 The method of step 1 consists of (2-benzyl-4,5-dimethyl-pan- 3 -yl)-(3 -second butyl-4 -methylchlorophenyl) -methanone (6.2 g, 15.8 mmol), boron tribromide (7.1 ml, 74.8 mmol), and dichloromethane (54 ml) to give the title compound as a solid (2 · 3 4 g, 4 1%): MS (EI): [H +] 3 6 0 〇 Step 2 2-Chun-4- (9-Jun-2. 3- Ershenmou-Saiyan f2. 3- b1-_ PAN-4 -a)-β-Second butyl phenol is printed by the Consumers' Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs 3-9 Step 6 method, 2 -Second-butyl-4-(2, 3 -Dimethyl-leaf [2,3-b] -Mepan-4-yl >-Persuasion (2.34 g, 6.5 mmol), bromine (0.69 ml, 13 mmol), potassium acetate (6.4 g, 65 mmol) and glacial acetic acid (65 ml) can be obtained as a solid of the title compound (0.63 g, 19%): MS (E I): [M +], 2 bromine Isotope-1 0 5-This paper size is in accordance with China National Standard (CNS) A4 (210 X 297 mm) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 Α7 Β7 V. Description of the invention ( , Yin) style, 516 (50%), 518 (100%), 520 (55%). Step 3 (R)-2-Γ 2 -Bromo-4-(Bu 湟 -2 · 3-U group- 苈1- ί 2 > 3-1) 1-blind-4_some) -6 ~ first > butyl—one 3 two.—this-propionamidine 49 method of step 6 from 2-bromo -4- (9-bromo'2,3-dimethyl-naphthalenepyrene [2,3-bbubipan-4-yl) -6-second butylphenol (0.63 g, 1.2 mmol) (S) methyl-2-hydroxy-3-phenylpropanoate (0.44 g, 2.4 mmol), triphenylhydrazone (0.64 g, 2.4 mmol), diethyl azodicarboxylate (0 , 38 g, 2.4 mmol) and anhydrous benzene (2.4 ml), and reacted at room temperature for 5 days to obtain an oil (0.60 g, 72%), which can be used without purification. The method of step 7 of Example 49 is prepared from (R > -2 [2-bromo-4- (9-bromo-2, 3-dimethyl-naphthalenepyrene [2,3-b] -blazepan-4-yl ) -6-Second-butyl phenyl carbamoyl 3-phenylpropionate (0.55 g, 0.73 mmol), KOH solution (1.6 ml of 1 N solution, 1.6 mmol), tetrahydrofuran (7.5 ml ), And methanol (2.5 ml) to obtain the title compound foam (0.26 g, 48%): MS (EI): [Μ +], 2 bromine isotope pattern, 6 6 4 (1 4%), 6 6 6 (2 6%), 668 (14%); Anal. Calc-for C33H30Br 203S: C, 59.47, H, 4.54, N, 0.00. Found: C, 59.44, Η, 4.81, N, 0. 03〇 Example 43 (R)-2-"2 -Hai-4- (9-Zhang-2. 3 dimethyldimethylfluorene" 2, 3-b 1 -_ Hope-4-a)- Yirong Argon 1-3-Mo Yan-Acid-Step 1 (2-Xin Mou-4 · 5-Nita 崠 pan-3-yl)--(3- E Mou-4-108- This paper size Applicable to China National Standard (CNS) A4 specification (210 X 297 mm) ------------------- Order --------- line (please read first (Notes on the back then fill out this page) A7

經濟部智慧財產局員工消費合作社印製五、發明說明（β) g g莶某）甲釀仿例49步驟1之方法，由3 -乙基-對-大_番醇酸（5·*^’ 27»?毫莫耳，RN-22934-35-6)，草醯氯（2·7 毫升 ’ 3〇· 毫荑耳），Ν，Ν-二甲基甲醯胺（2滴），2， 3 -二甲基5 节_吩（6·7克，33·2毫莫耳），氯化錫（IV)(3.6毫升， 3〇·5毫莫耳），及無水二氯甲烷（17?毫升），可製得標題化合物之油（5.2 克，51%)，（DMS0-d6): (ϊ?·59-7·54 (®，2Η), 7·25_7·ΐΠπι，3Η)，7.09-7.04(bi,3H)，3.87(S， 3Η), 3.84(s,2H), 2.57(q,2H), 2.26(s,3H), 1.82(d, 3H), l.l〇(t,3H); MS(+FAB): [M+H]365; Anal. Calc, for C23h 2 4 0 2 S: C, 7 5.7 9, H,6.64, N , 0 . 〇〇 , f〇und ： C, 75.34, H.6.72, N, 0.00〇步驟2 2-乙某-4- (2· 3-二甲莖駢「2· 3-上上^吩-卜基丄^Printed by the Employees' Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. 5. Description of the invention (β) gg 莶) The method of step 1 of the sample 49 of brewing. 27 »? Mole, RN-22934-35-6), chloramphenicol (2.7 ml '3 · m · mol), Ν, Ν-dimethylformamide (2 drops), 2, 3-Dimethyl 5-Methylphene (6.7 grams, 33.2 millimoles), tin (IV) chloride (3.6 ml, 30.5 millimoles), and anhydrous dichloromethane (17? Ml) to give the title compound as an oil (5.2 g, 51%), (DMS0-d6): (ϊ? 59-7 · 54 (®, 2Η), 7.25_7 · ΐΠπι, 3Η), 7.09- 7.04 (bi, 3H), 3.87 (S, 3Η), 3.84 (s, 2H), 2.57 (q, 2H), 2.26 (s, 3H), 1.82 (d, 3H), ll (t, 3H); MS (+ FAB): [M + H] 365; Anal. Calc, for C23h 2 4 0 2 S: C, 7 5.7 9, H, 6.64, N, 0. 〇〇, f〇und: C, 75.34, H.6.72, N, 0.00〇 Step 2 2-Ethyl-4- (2 · 3-Dimethyl stem

二 I 仿例49步驟2之方法，由（2-苄基-4, 5-二甲基-睹盼 - 3-基）-(3 -乙基-4-甲氣苯基）-甲酮（6·ι克，16.7 毫莫耳），三溴化硼（7· 1毫升，75· 4毫荑耳），及二氯甲烷（58毫升），可製得標題化合物之固體（2.6克，4 6 % ) : ( D M S 0 - d 6 ) : 3 7 · 4 9 ( s，1 Η )，8 · 4 2 ( s , 1 Η )，7 · 9 3 (d，lH), 7.47(d，lH)，7·43(®，1Η)，7·33(Η1，1Η)，7·〇2 -6.90(m 含一單線 ί 6.94，3H)，2.73u2U〇mplex 和，ABX pattern， 2H，旋轉異構物），2e4〇(s 3H丨，1β15 (t , 3 Η ) ； M S ( E I ) : [ M + ] 3 3 2 〇步驟 3 ill二二Ι-ϋ」：2 里某一繁 _「2 · 3 _ b Ί -107- 本紙張尺度適用中國國家標準（CNS)A4規格（210 x 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7 五、發明說明（、4) -睐盼-4-某）- 6 -乙荣氬某1 - 3-茱丙酴甲酯仿例39步驟6之方法，由2-乙基-4- ( 2，3-二甲基-萊駢[2，3-b卜瞎盼-4-基）-酚（2·6克，7·8毫莫耳），溴（〇·83毫升，15.7毫莫耳），乙酸鉀（7·7克，78·5 毫莫耳），及冰醋酸（78毫升）可製得標題化合物之固體（〇·73克），其可不經純化直接使用。仿例4 9步驟6之方法，由2 -溴-4——（9 -溴-2，3 -二甲基 -萘駢[2，3 - b卜瞎盼-4 -基）-6 -乙酚（0 · 7 3克，1 · 5毫莫耳），（S ) - 2 -羥基-3 -苯丙酸甲酯（0 · 5 4克，3 · 0毫莫耳），三苯隣（0·78克，3.0毫莫耳），偶氮二羧酸二乙酯（0·47毫升，3·0毫莫耳）及無水苯（3·0毫升），於室溫下反應5天可製得油（0.58克，60%) : (DMS0- d8) : δ 8 · 1 9 ( d，1Η)，7 · 6 5 (in，1Η)，7 · 54-7 · 2 2 (Μ 含一單線 7·32,9Η), 5.09 和 5·01(二 t.，lH，旋轉異構物），3 · 6 0 和 3 · 5 6 (二 s，3 Η，旋轉異構物），3 . 4 5 - 3 · 2 5 (complex m， 2H，旋轉異構物），2.78-2.50(complex m, A B X p a 11 e r η , 2 Η ) , 2 · 4 2 和 2 · 4 3 (二 s，3 Η，旋轉異構物），1 · 5 9 和 1 . 5 4 (二 s，3 Η，旋轉異構物），1 · 0 9 和1.07(二 t，3 Η 5旋轉異構物）。步驟4 ( R ) - 2 - Γ 2 -淳- 4 - ( 9 -溥-2 . 3 -二甲基-養駢「2· 3-bl-B富盼-4-某）氳某1-3-茱丙酴仿例4 9步驟7之方法，由（R ) - 2 [ 2 -溴-4 - ( 9 -溴- 2， 3 -二甲基-萘駢[2，3 - b ]-睹吩-4 -基）-6 _乙苯氣基]-3 -苯丙酸甲酯（0.41克，0.63毫莫耳），Κ0Η溶液（1.3毫 -1 08- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) 訂---- 線· 510900 A7 _B7_ 五、發明說明 (請先閱讀背面之注意事項再填寫本頁) 升之1N溶液，1·3毫莫耳），四氫呋喃（4·5毫升），及甲醇（1.5毫升）可製得標題化合物之淡黃色固體（0.38 克，95%) : (DMS0-d6): J13.05(br, S,1H), 8.20((1, ]Η),7β65(«ι,1Η), 7·54-7·18(ιη，9Η)，5·05(ι»，1Η),3·33 (m , 2 Η ) , 2.90-2.50(complex m , A B X pattern, 2 H ), 2 . 4 3 和 2 · 4 1 (二 s，3 H ,旋轉異構物），1 · 5 8 和 1 · 5 3 (二 s， 3 Η，旋轉異構物），1 · 1 0和1 · 0 9 (二 t，3 Η，旋轉異構物） ;M S ( - E S I ) : [ Μ - Η ]，2 溴同位素式樣，6 3 5 ( 4 4 % )， 6 3 7 ( 1 0 0 % ) , 6 3 9 ( 6 2 % ) ; Anal . Calc . for C3 1H26Br203S : C , 5 8 . 3 2 , Η，4 ·11，N , 0 . 00 . Found : C，58.11，H , 4 . 32 , Ν，0·18ο 例44 (R) -2 -「4- (9 -溴-2, 3-二申某-養駢 Γ2. 3- bl -睐盼 -4 -某）-β -黑丙茱氳某1- 3 -蒹丙酴步驟 1 (2R) -2 -「4- (9-淳-2, 3-二甲某-赛駢「2. 3- bl 經濟部智慧財產局員工消費合作社印製 -8富盼-4 -某）-2 -缇丙茱氫某1 - 3 _茱丙酴甲酯彷例4 9步驟6之方法，由4 - ( 9 -溴-2，3 -二甲基-#駢 [2，3-b卜瞎盼-4-基）-2，6 -異丙酚（0·26克，0.67毫莫耳），（S) -2-羥基-3-苯丙酸甲酯（0 · 32克，1 · 8毫莫耳），三苯_ (0.46克，1.8毫莫耳），偶氮二羧酸二乙酯（〇·28毫升，1·8毫莫耳）及無水苯（7·0毫升），於油浴（9 G °C )下反應4 . 5小時可製得標題化合物之白色固體（0·15克，38%):(DMS0-d6):(y8·18(ffi,lH)， 7·6 6- 7·58(βι，1Η)， 7.50-7.40(ra,2H), 7.40-7.30(ffl,4H) -109- 本紙張尺度適用中國國家標準（CNS)A4規格（210 χ 297公釐） 510900 A7 _B7_ 五、發明說明（（d) ，7*30-7,2 0(m，1 Η)，7.14-7.04(m, 2H)，6.92-6.87 (請先閱讀背面之注意事項再填寫本頁) (m，1 Η )，5 · 2 7 (t，1 Η )，3 · 7 0 和 3 · 6 5 (二單線，3 Η，旋轉異構物），3.40-3.20(m，3H)， 2.40(s，3H)， 1.49(s，3H) ，1 · 1 5和]…1 3 (二雙線，3 Η，旋轉異構物），1 · 0 6和1 . 0 4 (二雙線，3H，旋轉異構物）。步驟 2 (21?)-2-「4-(9-湟-2,3-二申某-_酣「2.3-131 -除盼-4 -某）_ 2 -墨丙茱氩某1 - 3-茱丙酴仿例4 9步驟7之方法，由（2 Γ) - 2 [ 4 - ( 9 -溴-2，3 -二甲基-萘駢[2，3-b卜晴盼-4-基）-2-異丙苯氧基]-3-苯丙酸甲酯（0.15克，0·25毫莫耳），Κ0Η溶液（0.5毫升之1Ν溶液，0·5毫莫耳），四氫呋喃（6毫升），及甲醇 (2毫升）可製得標題化合物之白色固體（0.14克，95%)·· (DMS0-d6) : 13.14(寬 s，lH)，8.18-8.15(m，lH)， 7 . 8 4 - 7 . 5 8 (in , 1 Η ) , 7 . 4 8 - 7 . 3 1 ( m , 6Η)， 7 . 3 0 - 7 . 2 2 (ffl, 1 Η)， 7.11-7.04(和，2Η)， 6·90 - 6·85(ϊπ，1Η)， 5.07(1，1Η) • 3 · 3 9 - 3 · 1 8 ( m，3 H )，2 · 4 1 和 2 · 4 0 (二單線，3 Η，旋轉異經濟部智慧財產局員工消費合作社印製構物），1 · 5 1和1 · 4 9 (二單線，3 Η，旋轉異構物），1 · 1 5 和1·14(二雙線，3Η，旋轉異構物），1.G4和1.03(二雙線，3 Η，旋轉異構物）；M S ( E I ) : [ Μ + ]，1溴同位素式 m , 5 7 2 / 5 7 4 ; Anal. Calc , for C32H29Br03S : C,67.01, H, 5.10, N5 0.00. Found: C,67.19, H , 5 . 4 7 , N，0 . 0 3 〇例45 (R ) _2 -「2-環戍某-4-（2、3~ 二甲某-養酣 Γ2. 3-bl - -110- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 五、發明說明（、。9) jjjl分-4_某）-¾氩某1-3-¾丙酴步驟1 (2 -苄某-4* 5-二瞎盼-3-某）-(3-環ft甚-4 - 甲氩茱某1 -甲酬於含3-環戊基-對-大㈣香醇酸（5·0克，27·7毫莫耳， R Ν - 5 9 2 1 6 - 8 2 - 9 )之無水二氯甲烷（6 0毫升），於室溫及氮氣下加入草醯氯（2, 4毫升，27 .2毫莫耳）及Ν， Ν-二甲基甲醯胺（2滴）。攪拌1 . 5小時後減壓濃縮。溶於二硫化磺（3 2毫升）並加至2 , 3 -二甲基-5 -苄睹盼 (5」克，2 5 · 0毫莫耳）。於-7 8 °C及氮氣下加入氯化錫 (IV) ( 2 · 9毫升，25 · G毫莫耳），於室溫下攪拌4小時。倒至冰水中（2 0 0毫升）並以***萃取（2 0 0毫升）。將 ***層以重碳酸鈉（50毫升）洗2次並以食鹽水（50毫升）洗1次。減壓濃縮並層析以石油醚：乙酸乙酯（9 5 : 5 )可製得標題化合物之琥珀色油（4.8克，525〇，（0^^0-(16):占 7.61-7.54 (m, 2H), 7.24-7.14 (m, 3H), 7.08-7.02 (m, 3H), 3.87 (s, 3H), 3.84 (s, 2H), 3.42-3.30 (m, 1H), 2.26 (s, 3H), 2.00-1.85 (m, 2H), 1.81 (s, 3H), 1.74-1.58 (m, 4H)，1.48-1.36 (m, 2H); MS(EI): [M+] 404; Anal· Calc· for C26H2802S: C， 77.19, H, 6.98, N, 0.00. Found: C, 76.26, H, 7.24, N, 0.04. 步驟2 2 -環戍某-4 -（ 2 . 3 -二申某-赛駢「2 , 3 -b」二Jt_ 盼-4-甚）於含（2-苄基-4，5_二甲晴吩-3-基）-(3-環戊基-4-甲氣苯基卜甲酮（4.8克，11.7毫奠耳）之無水二氯甲烷U0 毫升），於-7 8 °C及氮氣下，於2 0分内滴加入三溴化硼U · 6 毫升，37 . 6毫奠耳）。於室溫下攪拌22小時。倒至冰水中 (6 0 0毫升）並以***萃取（8 0 0毫升）。將***層以水（5 0 0 -1 1 1 ~ 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) ---------訂---------線一經濟部智慧財產局員工消費合作社印製經濟部智慧財產局員工消費合作社印製 510900 A7 B7_ 五、發明說明毫升）洗2次並以食鹽水（ 5 0 0毫升）洗1次。減壓濃縮並層析以石油醚：乙酸乙酯（9 7 : 3 )可製得標題化合物之白色固體 (3 · 4克，7 8% )，mp 156-158°C; (DMSO-d6): S9.48(s，1H)，8.42 (s，1H), 7.93 (d, 1H), 7.46-7.41 (m, 2H), 7.35-7.30 (m, 1H), 7.00 (s, 1H), 6.95-6.90 (m, 2H), 3.38-3.28 (m, 1H), 2.39 (s, 3H), 1.99-1.90 (m, 2H), 1.68-1.47 (m, 6H), 1.60 (s, 3H); MS(EI): [M+] 372; Anal. Calc, for C25H240S: C, 80.60, H, 6.49, N, 0.00. Found: C, 80.39, H, 6.43, N, 0.04. 步驟3 (R) -2-！~2-擐戍某-4- (2· 3 -二甲某-赛駢「2 . 3 _ h 睐盼-4 -甚）-茱氬某1 Ί荣丙酴申酯- 彷例49f之方法，由2-璟戊基-4- (2，3-二甲基-蔡駢 I: 2 9 3-b卜瞎吩_4_基）-酚（0 · 4克，1」毫莫耳），（S) -2-羥基-3-苯丙酸甲酯（0.29克，1·6毫莫耳），三苯瞵 (〇·42克，1·6毫莫耳），偶氮二羧酸二乙酯（0·25毫升，1.6毫莫耳）及無水苯（6.0毫升），於油浴（80°C) 下反應6小時可製得白色固體（0·26克，46%) : (DMS0- d6) : δ 8.44(s,lH),7.94(d,lH), 7 6 43 - 7 . 26 ( m , 8 Η ), 7.08-7.0 1 (m，2H)，6.88-6.85(m，lH)，5.24(dd，lH)， 3 e 7 0 和 3 · 6 6 (二單線，3 H，旋轉異構物），3 · 4 2 - 3 · 2 0 ( ®， 3H)，2.38(s，3H)，2·02-}·30(ϊ» 含二單線 51·52， 1 1Η) 〇步驟 4 ( R) ( 2 . 3 娜 2·^^^ -嗦盼爾4-某)""篆氛某1-3 -兼丙酸仿例49步驟7之方法，由（R) -2[2-璟戊基-4-(2， 3-二甲基駢[2，3-b卜_盼-4-基）-苯氣基]-3-苯丙酸甲酯（0.22克，0.41毫莫耳Κ0Η溶液（0.82毫升 -1 12- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 _______B7__ 五、發明說明（之1 N溶液，〇 · 8 2毫莫耳），四氫呋喃（1 2毫升），及甲醇（4毫升）可製得標題化合物之白色固體（0 · 2 1克， 95%) ： Opt. Rot. [a]25/D=-8.19° (8.549mg/mL, (：!1(：13);(_30-(}6):3 13.10(寬8，1{1)，8.43(<},11〇， 7 · 9 3 ( m，1 fl )，7 · 4 3 繼 7 · 2 0 ( m，8 Η )，7 · 0 7 - 7 · 0 2 ( w，2 Η )， 6·88-6·84(ηι，1Η)，5·03 和 5.07(二 dd，lH,旋轉異構物），3 . 3 9 - 3 . 1 7 ( m，3 Η )，2 · 3 8 和 2 . 3 7 (二單線，3 Η，旋轉異構物），1 · 9 0 (η»，1 Η )，1 · 7 6 U，1 Η )，1 · 7 0 - 1 · 3 2 ( ffi 含二單線占 1 · 5 4 和 1 · 5 2 (旋轉異構物），9 Η ) ; M S ( Ε I ) : [ Μ + ] 5 2 0 ; Anal. C a 1 c . f o r C34H 3 2 0 3 S : C，78.43，Η，6·19, N , 0 . 00 Found : C , 7 7 . 9 6 , H , 6 . 4 0 , N , 0 . 0 2 ; Analytical HPLC 顯示主成分（9 6 · 9 % )。例46 (R) -2-「4- (2 , 3-二甲某-赛駢「2. 3-hl -睹盼-4-某）申荥氫某3 -茱丙酴Di I The method of step 2 of Example 49 consists of (2-benzyl-4, 5-dimethyl-sulfan-3-yl)-(3-ethyl-4-methylphenyl) -methanone ( 6 · g, 16.7 mmol), boron tribromide (7.1 ml, 75.4 mmol), and dichloromethane (58 ml) to give the title compound as a solid (2.6 g, 4 6%): (DMS 0-d 6): 3 7 · 4 9 (s, 1 Η), 8 · 4 2 (s, 1 Η), 7 · 9 3 (d, lH), 7.47 (d, lH ), 7.43 (®, 1Η), 7.33 (Η1, 1Η), 7.02-6.90 (m with a single line ί 6.94, 3H), 2.73u2Umplex and ABX pattern, 2H, rotation difference Structure), 2e4〇 (s 3H 丨, 1β15 (t, 3 Η); MS (EI): [M +] 3 3 2 〇 Step 3 ill 22 Ⅱ-ϋ ”: 2 · 3 _ b Ί -107- This paper size applies to China National Standard (CNS) A4 (210 x 297 mm) -------------------- Order- ------- line (Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7 V. Description of the Invention (, 4)-Favor -4- -6-Ethyl Argon 1-3-Juprofen Methyl Example 39 steps The method of 6 consists of 2-ethyl-4- (2,3-dimethyl-lysamine [2,3-b bublend-4-yl) -phenol (2.6 g, 7.8 mmol) Ear), bromine (0.83 ml, 15.7 mmol), potassium acetate (7.7 g, 78.5 mmol), and glacial acetic acid (78 ml) to obtain the title compound as a solid (0.73 G), which can be used directly without purification. Example 4 9 The method of step 6 consists of 2-bromo-4 —— (9-bromo-2,3-dimethyl-naphthalene 骈 [2,3-b Pan-4 -yl) -6-ethylphenol (0.73 g, 1.5 mmol), (S)-2-hydroxy-3 -phenylpropionate methyl ester (0.54 g, 3 · (0 mmol), triphenyl o- (0. 78 g, 3.0 mmol), diethyl azodicarboxylate (0.47 ml, 3.0 mmol) and anhydrous benzene (3.0 ml) ), Oil can be prepared by reaction at room temperature for 5 days (0.58 g, 60%): (DMS0-d8): δ 8 · 1 9 (d, 1Η), 7 · 6 5 (in, 1Η), 7 · 54-7 · 2 2 (M with a single line of 7.32,9Η), 5.09 and 5.01 (two t., LH, rotamers), 3 · 6 0 and 3 · 5 6 (two s, 3 Hydrazone, rotamer), 3.4 5-3 · 2 5 (complex m, 2H, rotamer ), 2.78-2.50 (complex m, ABX pa 11 er η, 2 Η), 2 · 4 2 and 2 · 4 3 (two s, 3 Η, rotamers), 1 · 5 9 and 1.5 4 (two s, 3 Η, isomers), 1.09 and 1.07 (two t, 3 Η, 5 isomers). Step 4 (R)-2-Γ 2 -chun- 4-(9-溥 -2. 3 -dimethyl-trophocyanine "2 · 3-bl-B FUPAN-4-some) 氲 some 1-3 -Fructus erysiperisin Example 4 9 The method of step 7 is based on (R)-2 [2 -bromo-4-(9 -bromo-2,3-dimethyl-naphthalenepyrene [2,3 -b]- Phenyl-4 -yl) -6 _ethylbenzeneyl] -3 -phenylphenylpropionate (0.41 g, 0.63 mmol), K0Η solution (1.3 mmol-1 08- This paper size applies to Chinese National Standards (CNS ) A4 size (210 X 297 mm) (Please read the precautions on the back before filling this page) Order ---- Line · 510900 A7 _B7_ V. Description of the invention (Please read the precautions on the back before filling this page) A 1N solution (1.3 mmol), tetrahydrofuran (4.5 ml), and methanol (1.5 ml) gave the title compound as a pale yellow solid (0.38 g, 95%): (DMS0-d6): J13.05 (br, S, 1H), 8.20 ((1,] Η), 7β65 («ι, 1Η), 7.54-7 · 18 (ιη, 9Η), 5.05 (ι», 1Η) , 3.33 (m, 2 Η), 2.90-2.50 (complex m, ABX pattern, 2 H), 2. 4 3 and 2. 4 1 (two s, 3 H, rotomer), 1.5 8 and 1 · 5 3 (two s, 3 Η, rotamers), 1 · 1 0 and 1 · 0 9 (di-t, 3 fluorene, rotamer); MS (-ESI): [M-fluorene], 2 bromine isotope pattern, 6 3 5 (4 4%), 6 3 7 ( 1 0 0%), 6 3 9 (6 2%); Anal. Calc. For C3 1H26Br203S: C, 5 8. 3 2, Η, 4 · 11, N, 0. 00. Found: C, 58.11, H , 4.32, Ν, 0 · 18ο Example 44 (R) -2-"4- (9 -Bromo-2, 3-Second-Sangyang-Liang 骈 2. 3- bl -Lanpan-4 -Sina)- β-Heizhu Zhuan 1- 3 -Yan Bing Step 1 (2R) -2-"4- (9-Jun-2, 3-Dimethyl-a-Sai" "2. 3- bl Intellectual Property of the Ministry of Economic Affairs Printed by the Bureau's Consumer Cooperative Cooperative -8 Fupan-4 -a) -2-teprodone hydrochloride 1-3 _ acetic acid methyl ester model 4 9 step 6 method, from 4-(9 -bromo-2 , 3-dimethyl- # 骈 [2,3-b bublend-4-yl) -2,6-propofol (0.26 g, 0.67 mmol), (S) -2-hydroxyl Methyl-3-phenylpropionate (0.32 g, 1.8 mmol), triphenyl- (0.46 g, 1.8 mmol), diethyl azodicarboxylate (0.28 ml, 1 8 mmol) and anhydrous benzene (7.0 ml), reacted in an oil bath (9 G ° C) for 4.5 hours to obtain the title compound as a white solid (0.15g, 38%): (DMS0-d6): (y8 · 18 (ffi, lH), 7.6 6- 7.58 (βι, 1Η), 7.50-7.40 (ra, 2H), 7.40 -7.30 (ffl, 4H) -109- This paper size is applicable to Chinese National Standard (CNS) A4 specification (210 χ 297 mm) 510900 A7 _B7_ V. Description of the invention ((d), 7 * 30-7, 2 0 ( m, 1 Η), 7.14-7.04 (m, 2H), 6.92-6.87 (please read the notes on the back before filling this page) (m, 1 Η), 5 · 2 7 (t, 1 Η), 3 · 7 0 and 3 · 6 5 (two single wires, 3 Η, rotational isomers), 3.40-3.20 (m, 3H), 2.40 (s, 3H), 1.49 (s, 3H), 1 · 1 5 and] … 1 3 (two double lines, 3 amidines, rotomers), 1.06 and 1.0 4 (two double lines, 3H, rotomers). Step 2 (21?)-2- 「4- (9- 湟 -2,3-Second Shenmou-_ 酣」 2.3-131 -Danpan-4 -Mom) _ 2-Mo Bing Ju Ar 1-3 -Jujube Example 4 The method of step 7 from (2 Γ)-2 [4-(9 -bromo-2,3-dimethyl-naphthalenepyrene [2,3-b Methyl) -2-cumyloxy] -3-phenylpropanoate (0.15 g, 0.25 mmol), K0Η solution (0.5 ml of 1N solution, 0.5 mmol), tetrahydrofuran ( 6 ml) and methanol (2 ml) to obtain the title compound as a white solid (0.14 g, 95%) ... (DMS0-d6): 13.14 (width s, lH), 8.18-8.15 (m, lH), 7. 8 4-7. 5 8 (in, 1 Η), 7.4 8-7. 3 1 (m, 6 Η), 7. 3 0-7. 2 2 (ffl, 1 Η), 7.11-7.04 (And, 2Η), 6.90-6.85 (ϊπ, 1Η), 5.07 (1, 1Η) • 3 · 3 9-3 · 1 8 (m, 3 H), 2 · 4 1 and 2 · 4 0 (two single lines, 3 Η, printed structures of the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Rotating Economy), 1 · 5 1 and 1 · 4 9 (two single lines, 3 Η, rotary isomers), 1 · 1 5 And 1.14 (two double lines, 3 Η, rotomer), 1.G4 and 1.03 (two double lines, 3 Η, rotomer) MS (EI): [Μ +], 1 bromine isotope formula m, 5 7 2/5 7 4; Anal. Calc, for C32H29Br03S: C, 67.01, H, 5.10, N5 0.00. Found: C, 67.19, H, 5.4 7, N, 0.03 〇 Example 45 (R) _2-"2-Cyclopsium-4- (2, 3 ~ Dijiamou-Yangyang Γ 2. 3-bl--110- This paper The scale is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 510900 A7 V. Description of the invention (, .9) jjjl points -4_some)-¾ arg 1-3-¾ propyl step 1 (2 -Benzyl-4 * 5-diblazepan-3-some)-(3-cyclo ft even-4-methyl arsenate 1-methyl benzoate-containing 3-cyclopentyl-p-germanylic acid (5 • 0 g, 27.7 mmol, R Ν-5 9 2 1 6-8 2-9) in anhydrous dichloromethane (60 ml), add chloramphenicol (2, 4 at room temperature under nitrogen) Ml, 27.2 mmol) and N, N-dimethylformamide (2 drops). After stirring for 1.5 hours, it was concentrated under reduced pressure. Dissolve in sulfide disulfide (32 ml) and add to 2,3-dimethyl-5 -benzylazine (5 "g, 25.0 mmol). Add tin (IV) chloride (2.9 ml, 25 · G mmol) at -78 ° C under nitrogen, and stir at room temperature for 4 hours. Pour into ice water (200 ml) and extract with ether (200 ml). The ether layer was washed twice with sodium bicarbonate (50 ml) and once with brine (50 ml). Concentrated under reduced pressure and chromatographed with petroleum ether: ethyl acetate (95: 5) to give the title compound as an amber oil (4.8 g, 5250, (0 ^^ 0- (16): 7.61-7.54 ( m, 2H), 7.24-7.14 (m, 3H), 7.08-7.02 (m, 3H), 3.87 (s, 3H), 3.84 (s, 2H), 3.42-3.30 (m, 1H), 2.26 (s, 3H), 2.00-1.85 (m, 2H), 1.81 (s, 3H), 1.74-1.58 (m, 4H), 1.48-1.36 (m, 2H); MS (EI): [M +] 404; Anal · Calc · For C26H2802S: C, 77.19, H, 6.98, N, 0.00. Found: C, 76.26, H, 7.24, N, 0.04. Step 2 2-Huan Mou-4-(2. 3-Two Shen Mou-Race骈 "2, 3 -b" DiJt_pan-4-even) in (2-benzyl-4,5_dimethylmethan-3-yl)-(3-cyclopentyl-4-methylbenzene Glycolone (4.8 g, 11.7 millimoles) in anhydrous dichloromethane U0 ml) was added dropwise boron tribromide U · 6 ml, 37 ° C at -78 ° C under nitrogen. 6 millimoles). Stir for 22 hours at room temperature. Pour into ice-water (600 ml) and extract with ether (800 ml). Ether layer with water (50 0 -1 1 1 ~ ~ Paper size applies to China National Standard (CNS) A4 (210 X 297 mm) (Please read the Please fill in this page for the matters needing attention) --------- Order --------- Printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs Printed 510900 A7 B7_ V. Description of the invention (ml) Washed twice and washed once with brine (500 ml). Concentrated under reduced pressure and chromatographed with petroleum ether: ethyl acetate (97: 3) to obtain the title compound as a white Solid (3.4 g, 78%), mp 156-158 ° C; (DMSO-d6): S9.48 (s, 1H), 8.42 (s, 1H), 7.93 (d, 1H), 7.46- 7.41 (m, 2H), 7.35-7.30 (m, 1H), 7.00 (s, 1H), 6.95-6.90 (m, 2H), 3.38-3.28 (m, 1H), 2.39 (s, 3H), 1.99- 1.90 (m, 2H), 1.68-1.47 (m, 6H), 1.60 (s, 3H); MS (EI): [M +] 372; Anal. Calc, for C25H240S: C, 80.60, H, 6.49, N, 0.00. Found: C, 80.39, H, 6.43, N, 0.04. Step 3 (R) -2-! ~ 2- 擐戍某 -4- (2 · 3-dimethyl a-Sai 骈 "2. 3 _ h favor Pan -4-even)-Zhu Xi a certain 1 rongrong propyl ester-the method of Example 49f , 2-Pentamyl-4- (2,3-dimethyl-Ceamidine I: 2 9 3-b-Buphenphen_4-yl) -phenol (0.4 g, 1 "mol) , (S) methyl 2-hydroxy-3-phenylpropionate (0.29 g, 1.6 mmol), triphenylhydrazone (0.42 g, 1.6 mmol), azodicarboxylic acid Diethyl ether (0.25 ml, 1.6 mmol) and anhydrous benzene (6.0 ml) were reacted in an oil bath (80 ° C) for 6 hours to obtain a white solid (0.26 g, 46%): ( DMS0- d6): δ 8.44 (s, lH), 7.94 (d, lH), 7 6 43-7.26 (m, 8 Η), 7.08-7.0 1 (m, 2H), 6.88-6.85 (m, lH), 5.24 (dd, lH), 3 e 7 0 and 3 · 6 6 (two single wires, 3 H, rotamer), 3 · 4 2-3 · 2 0 (®, 3H), 2.38 (s , 3H), 2 · 02-} · 30 (ϊ »with two single lines 51 · 52, 1 1Η) 〇 Step 4 (R) (2.3 Na 2 · ^^^-嗦 hope Seoul 4-some) " " The method of step 7 of a 1-3-propionic acid sample 49 is (R) -2 [2-fluorenyl-4- (2, 3-dimethylphosphonium [2,3-b BU_Pan-4-yl) -Benzenyl] -3-phenylpropanoate Ester (0.22 g, 0.41 millimolar K0Η solution (0.82 ml -1 12- This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) ------------- ------- Order --------- line (Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 _______B7__ V. Description of the invention (of 1 N solution, 0.82 mmol), tetrahydrofuran (12 ml), and methanol (4 ml) to obtain the title compound as a white solid (0.21 g, 95%): Opt. Rot. [ a] 25 / D = -8.19 ° (8.549mg / mL, (:! 1 (: 13); (_ 30-() 6): 3 13.10 (width 8,1 {1), 8.43 (<}, 11 〇, 7 · 9 3 (m, 1 fl), 7 · 4 3 Following 7 · 2 0 (m, 8 Η), 7 · 0 7-7 · 0 2 (w, 2 Η), 6.88-6 · 84 (ηι, 1Η), 5.03 and 5.07 (didd, lH, rotamer), 3. 3 9-3. 1 7 (m, 3 Η), 2 · 3 8 and 2. 3 7 (Two single lines, 3 Η, rotational isomers), 1 · 9 0 (η », 1 Η), 1 · 7 6 U, 1 Η), 1 · 7 0-1 · 3 2 (ffi contains two single lines occupying 1 · 5 4 and 1 · 5 2 (rotomers), 9 Η); MS (E I): [Μ +] 5 2 0; Anal. 9 6, H, 6.4 0, N, 0.0 2; Analytical HPLC showed the main component (96. 9%). Example 46 (R) -2- "4- (2, 3-dimethylamine-Saiyan" "2. 3-hl-见盼 -4- 某"

步驟 1 ( R) -2- U - 4 -某）- 2. 6 -二申茱氩某Ί -3-茱丙酴申酯仿例4 9步驟6之方法，由4 - ( 2 , 3 -二甲基-萘駢[2，3 - b ] 盼-4-基）-2，6-二甲酚（0·4克，1·2毫莫耳），（S)-2- 羥基-3-苯丙酸甲酯（0·49克，2·7毫莫耳），三苯瞵（0·71 克，2·7毫莫耳），偶氮二羧酸二乙酯（0.36毫升，2.7毫莫耳）及無水苯（1 3毫升），於油浴（7 G〜8 6 °C )下反應1 0小時可製得白色固體（0·24 克，40%) :(DMSO-d6): δ 8.44 (s，1H)，7.94 (d，1H)，7.45-7.39 (m, 2H), 7.35-7.30 (m, 5H), 7.28-7.24 (m, 1H), 6.96 (s, 2H), 4.77 (t, 1H), 3.56 (s,3H), 3.34-3.25 (m, 2H), 2.39 (s, 3H), 2.22 (s, 3H), 2.17 (s, 3H), 1.56 (s, 3H); MS(EI): [M+] 494; Anal· Calc, for C32H30O3S: C，77,70，H，6.11，N，0.00· Found: C, 76.53, H, 5.85, N, 0.08. -113- 本紙張尺度適用中國國家標準（CNS)A4規格（210 x 297公釐） (請先閱讀背面之注意事項再填寫本頁)Step 1 (R) -2- U-4 -some)-2. 6-Dishenthium arginine-3-ruprosin ester Example 4 9 The method of step 6, from 4-(2, 3- Dimethyl-naphthalene [2,3-b] pan-4-yl) -2,6-xylenol (0.4 g, 1.2 mmol), (S) -2-hydroxy-3 -Methyl phenylpropionate (0.49 g, 2.7 mmol), triphenylhydrazone (0.71 g, 2.7 mmol), diethyl azodicarboxylate (0.36 ml, 2.7 Millimolar) and anhydrous benzene (13 ml), reacted in an oil bath (7 G ~ 86 ° C) for 10 hours to obtain a white solid (0 · 24 g, 40%): (DMSO-d6) : δ 8.44 (s, 1H), 7.94 (d, 1H), 7.45-7.39 (m, 2H), 7.35-7.30 (m, 5H), 7.28-7.24 (m, 1H), 6.96 (s, 2H), 4.77 (t, 1H), 3.56 (s, 3H), 3.34-3.25 (m, 2H), 2.39 (s, 3H), 2.22 (s, 3H), 2.17 (s, 3H), 1.56 (s, 3H) ; MS (EI): [M +] 494; Anal · Calc, for C32H30O3S: C, 77, 70, H, 6.11, N, 0.00 · Found: C, 76.53, H, 5.85, N, 0.08. -113- present Paper size applies to China National Standard (CNS) A4 (210 x 297 mm) (Please read the precautions on the back before filling this page)

510900 A7 _____B7___ 五、發明說明（（A) 步驟2 ( R) -2二丄4- ( 2 3-二申某-赛駢Γ2 , 3-bl-時盼 -4 '基）-21 6 -二田茱舊•某1Ί茱丙酸仿例4 9步驟7之方法，由（R ) - 2 - [ 4 - ( 2 , 3 -二甲基-萘駢[2，3-b]-睹盼-4-基）-2, 6-二甲苯氧基卜3- 苯丙酸甲酯（〇·23克，0.46毫莫耳），Κ0Η溶液（0·91 毫升之1 Ν溶液，0 · 9 1毫莫耳），四氫呋喃（1 2毫升） ,及甲醇（4毫升）可製得標題化合物之白色固體 (0·19克，8 6%) : Opt . Rot . [a]25/D = 33.04° (10.170 mg/mL,MeQH); (DMSO-d6): 6 12.9 (broad s, 1H), 8.44 (s, 1H), 7.94 (d, 1H), 7.45-7.40 (m, 2H), 7.35-7.22 (m, 6H), 6.95 (s, 2H), 4.70 (t, 1H), 3.25 (d, 2H), 2.38 (s, 3H), 2.24 (s, 3H), 2.22 (s, 3H), 1.56 (s, 3H); MS(EI): [M+] 480; Anal. Calc, for C31H2803S: C, 77.47, H, 5.87, N, 0.00. Found: C, 76.23, H, 5 · ? 7，N，0 · 0 3 ; A n a 1 y t i c a ] Η P L C 顯示主成分（9 4 · 6 % )。例47 (R ) -2 二J—4二(9 -溴 - 2 . 3 -二申某-苯駢 F 2 . 3 - h 1 -睐 P分 -4 -某）-2 -環戍茏氬某茱丙酴步驟1 乙酶2 -璟戊某-4 -（2> 3 -二申某-赛駢Γ2, 3-h飞 -睹盼-4-基）-¾酷將含2-環戊基-4- ( 2，3-二甲基-萘駢[2, 3-b]-B塞吩 - 4-基）-酚（2·8克，7·5毫莫耳）之無水吡啶（20毫升），於室溫及氮氣下滴加入乙酐（0 · 9 2毫升，9 · 8毫莫耳）。置於冰箱中。41小時後，稀釋並酸化以1(UHC1至ΡΗ1。以***（5 0 ()毫升）萃取，將***層以5 X H C 1 ( 1 0 0毫升），水（100毫升 X 2)，食鹽水（100毫升）洗後乾燥 -1 14- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） " ' (請先閱讀背面之注意事項再填寫本頁)510900 A7 _____B7___ V. Description of the invention ((A) Step 2 (R) -2 2 丄 4-(2 3 -2 Shenmou-sai 骈 Γ2, 3-bl- 时 hope-4 'base) -21 6 -2 Cornus officinalis · A method of a step 1 of 9 dogwood propionic acid according to step 9 from (R)-2-[4-(2, 3 -dimethyl-naphthalene 骈 [2,3-b]-见盼- 4-yl) -2,6-xyloxyb-methyl 3-phenylpropionate (0.23 g, 0.46 mmol), K0Η solution (0.91 ml of a 1 N solution, 0.91 mmol Moore), tetrahydrofuran (12 ml), and methanol (4 ml) to obtain the title compound as a white solid (0.19 g, 8 6%): Opt. Rot. [A] 25 / D = 33.04 ° ( 10.170 mg / mL, MeQH); (DMSO-d6): 6 12.9 (broad s, 1H), 8.44 (s, 1H), 7.94 (d, 1H), 7.45-7.40 (m, 2H), 7.35-7.22 ( m, 6H), 6.95 (s, 2H), 4.70 (t, 1H), 3.25 (d, 2H), 2.38 (s, 3H), 2.24 (s, 3H), 2.22 (s, 3H), 1.56 (s , 3H); MS (EI): [M +] 480; Anal. Calc, for C31H2803S: C, 77.47, H, 5.87, N, 0.00. Found: C, 76.23, H, 5 ·? 7, N, 0 · 0 3; Ana 1 ytica] Η PLC shows the main component (9 4 · 6%). Example 47 (R) -2 DiJ-4bis (9 -Bromo-2. 3 -Dishen-benzene骈 F 2. 3-h 1 -Prefer P points -4 -a) -2-Cyclopyrene, a certain cymbalone step-1 Enzyme 2-Aaron -4-(2 > 3-two Shenmou-Sai骈 Γ2, 3-h fe-span-4-yl)-¾ will contain 2-cyclopentyl-4- (2,3-dimethyl-naphthalene 骈 [2, 3-b] -B thiophene -4-yl) -phenol (2.8 g, 7.5 mmol) in anhydrous pyridine (20 ml), acetic anhydride (0.92 ml, 9.8 mmol) was added dropwise at room temperature under nitrogen. Ear). Place in the refrigerator. After 41 hours, dilute and acidify with 1 (UHC1 to PH1. Extract with ether (50 () ml)), extract the ether layer with 5 XHC 1 (100 ml), water (100 Ml x 2), salt water (100 ml), washed and dried -1 14- This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) " '(Please read the precautions on the back before filling (This page)

訂---------線I 經濟部智慧財產局員工消費合作社印製 510900 Α7 Β7 五、發明說明（0) (硫酸鎂）。減壓濃縮可得標題化合物之白色固體（3· 1克， 98%): (DMS0>d6): δ 8.48 (s, lH),7.97(d, 1H), 7.47-7.43 (m, 1H), 7.38-7.36 (m, 2H), 7.28 (s, 1H), 7.19 (d, 2H), 3.14 (quintet, 1H), 2.40 (s, 3H), 2.37 (s, 3H), 1.99-1.91 (m, 2H), 1.69-1.40 (m, 6H), 1.56 (s, 3H); MS(EI): [M+] 414; Anal. Calc, for C27H2602S: C, 78.23, H, 6.32, N, 0.00. Found: C, 77.68, H, 6.39, N, 0.04. 步驟2乙酸2 -環戊基，4 -（ 9 -海-2 . 3 -二g甚-玆餅 f 2 . 3 - b 1 -嗦盼-4 -某）-茱酯將含乙酸2 -環戊基-4 - ( 2，3 -二甲基-萘駢[2 , 3 - b ]- 睹吩-4-基苯酯（2.9克，7 .7毫莫耳）之無水二氯甲烷（68毫升）中加入氯化鐵（66毫克，0· 4 1毫奠耳）。置於氮氣下並冷卻至_78°C。避免光照射下及於15分内滴加入含溴（〇· 4 4毫升，8 .5毫莫耳）之無水二氯甲烷 (11毫升）。於-78°C下攪拌45分，加入稀釋亞硫酸鈉中止反應後倒至冰水中（2 0 0毫升）。以***萃取（3 0 0 毫升），將***層以水及食鹽水。減壓濃縮並層析以石油釀：乙酸乙酯（95:5)可製得標題化合物之白色固體 (2 . 7克，7 9% ) : (CDC13): δ 8.28 (d，1H)，7.58-7.52 (m，2H), 7.39·7·34 (m，1Η), 7.29 (d，1Η), 7·18 (dd，1Η), 7.14 and 7·13 (d, 1Η)，3·18 (quintet, 1Η), 2.44 (s, 3H), 2.40 (s, 3H), 2.06-2.02 (m, 2H), 1.75-1.45 (m containing a singlet at δ 1.60, 9H); MS(EI): [M+], 1 溴同位素式樣，492/494; Anal. Calc, for C27H25Br02S: C, 65.72, H, 5.11, N, 0.00. Found: C, 63.18, H, 4.96, N, 0.00. 步驟3 2-環戍基-4- (9-漳-2. 3 -二申某-赛_「2. 3- hi -睹盼-4 -某酚將含乙酸2 -璟戊基-4 - ( 2，3 -二甲基-萘駢[2 , 3 - b ] -瞎盼-4-基）-苯酯（2·7克，5·4毫莫耳）之四氫呋喃 (88毫升）及甲醇（30毫升），於室溫下滴加入Κ0Η溶 -1 1 5- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) 訂---------線，經濟部智慧財產局員工消費合作社印製 510900 A7 B7____ 五、發明說明（"4) 液（6 · 5毫升之1 N溶液，6 . 5毫莫耳）。1 · 5小時後減壓濃縮。結合以水（200毫升）及酸化以10%HC1至PH1。以 (請先閱讀背面之注意事項再填寫本頁) ***（3 0 0毫升）萃取，將***層以水洗2次後乾燥（硫酸銷）〇減壓濃縮可得檫題化合物之白色固醱（2·4克 ,100%) : _SO-d6): δ9·54 (s，1Η)，8.16 (d, 1Η)，7·61 (m, 1Η)，7·52 (s，1Η)，7.43 (m，1Η)，7·03 (s，1Η)，6.93 (m，2Η)，3·32 (m，1Η)，2·41 (s， 3H), 1.94 (m, 2H), 1.58 (s, 3H), 1.72-1.42 (m, 6H); MS(EI): [M+], 1 溴同位素式樣，450/452; Anal· Calc· for C25H23BrOS: C,66.52,H，5.13, N，0·00· Found: C, 67.17, H, 5.25, N, 0.04. 步驟 4 ( R ) 4 - U - ( 9 -溴-2 · 3 -二申某-棼 _「2 . 3 - h 1 -睹盼-4-某）-2 -擐戊茱氳某茱丙酴申酷仿例49步驟6之方法，由4- ( 9-溴-2 , 3-二甲基-萘駢 [2，3 - b ] - B書盼-4 -基）-2 -環戊酚（0 · 4克，0 · 8 9毫莫耳），（S) -2-羥基-3-苯丙酸甲酯（0 · 48克，2 · 7毫莫耳），三苯瞵（0 · 7 0克，2 · 7毫莫耳），偶氮二羧酸二乙酯 (0 · 4 2毫升，2 · 7毫莫耳）及無水苯（6 · 0毫升），於油浴（8 5 °C )下反應4 · 5小時可製得白色固體（0 · 1 9 克，34%) : (DMS0-d6): 8,17 (d，lH)，7.64-7.59 (βϊ,1Η),7.45-7.40(βι,2Η),7.38-7.24(ι,5Η)57.10-7.03 (m,2H)，6β90-6·86(ηι，1Η), 5·28-5β24(ιπ，1Η)，3·70 和經濟部智慧財產局員工消費合作社印製 3·6 6(二單線，3H，旋轉異構物），3·40-3·24(ηι，3Η)，2·40 (s，3H)，1·95-1·30(πι，8Η)，1.49(s，3H); MS(EI): [Μ+] ，1溴同位素式樣，6 1 2 / 6 1 4。步驟 5 ( R) - 2 - 1~ 4 - ( 9 -漳-2 · 3 -二甲基二養駢「2 · 3 - b 1 -睹盼-4-某）-2-琿戍荖氯基1 - 3:笨丙酸 -1 1 6- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 經濟部智慧財產局員工消費合作社印製 A7 B7 五、發明說明（Μ) (1 0 0毫升）萃取。將荦取液水洗2次（1 〇〇毫升），減濃縮並靨析以石油醚：乙酸乙酯（98:2)，碾製以石油醚可製得標題化合物之白色固體（1 · 2克，5 2 % ): 熔點 1 8 9 · 5 〜19 1°C;(DMSO-d6):S9.19(s，lH)，8.18(d，lH)，7.65- 7.61 (m, 1H), 7.50-7.47 (m, 2H), 7.33 (d, 1H), 7.11 (d, 1H), 3.42 (quintet, 1H), 2.43 (s, 3H)f 2.00-1.97 (m,2H ), 1.69-1.46 (m, 6H), 1.60 (s, 3H); MS(E1): [M+], 2 溴同位素式樣，528 (46%)，530 (100%). 532 (52%): Ληιιΐ, Calc, for C25H22Br20S: C, 56.62, H，4.18, Ν,0·00· Found: C, 55.78, Η, 4.12, Ν,0·05. 步驟 2 一二—4二（9 -淳-2· 二申甚-黨_ &二 _1-8:環戍茱氧華]Ί 菜丙酴申酯將含2-溴-4- (9-溴-2, 3-二甲基-萘駢[2，3外卜_盼 -4 -基）-2，6 -環戊酚（1 · 2 克，2 · 2 毫莫耳），（S ) - 2 - 羥基-3-苯丙酸甲酯（0.60克，3·3毫莫耳），及三苯隣 (0*87克，3.3毫莫耳）之無水苯（20毫升），於室溫及氮氣下滴加入偶氮二羧酸二乙酯（0 . 5 2毫升，3 . 3毫莫耳）。於室溫下5小時後趿附至矽謬，並層析以石油醚：乙酸乙酯（9 5 : 5)可製得標題化合物之白色固體（丨.2 克，86%):熔點 167 〜168«5°C ; NMR (CDC13) : 8.28 (m?lH),7.58-7.47(m,2H), 7.41-7.36(ro,2H), 7.34-7 · 2 5 ( ，5 Η )，7 . 18 ( 1 Η )，5· 11和 5 · 0 2 (二 d d，1 H，旋轉異構物），3·66和3·6 3(二s，3H,旋轉異構物），3.58- 3 · 3 3 U，3 Η ) , 2 · 4 4 和 2 · 4 3 (二 s，3 Η ,旋轉異構物），2 , 2 0 (爾，1 Η )，1 . 9 5 ( κι，1 Η )，1 · 7 5 - 1 · 3 2 ( m 含二單線 d 1 · 6 3 和 1 · 6 9 (旋轉異構物），9 Η ) ; M S ( E I ) : [ Μ + ]，溴同位素式 -1 1 8 一本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) if 訂------|!線* 510900 經濟部智慧財產局員工消費合作社印製 A7 B7 五、發明說明（樣，6 90( 4 6 %), 692(100%)，694(54%);八11&1*(^1(!· for C35H32Br203S: C, 60.70, Η, 4.66, Ν, 0.00.Order --------- Line I Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 Α7 Β7 V. Description of the Invention (0) (magnesium sulfate). Concentrated under reduced pressure to give the title compound as a white solid (3.1 g, 98%): (DMS0 > d6): δ 8.48 (s, lH), 7.97 (d, 1H), 7.47-7.43 (m, 1H), 7.38-7.36 (m, 2H), 7.28 (s, 1H), 7.19 (d, 2H), 3.14 (quintet, 1H), 2.40 (s, 3H), 2.37 (s, 3H), 1.99-1.91 (m, 2H), 1.69-1.40 (m, 6H), 1.56 (s, 3H); MS (EI): [M +] 414; Anal. Calc, for C27H2602S: C, 78.23, H, 6.32, N, 0.00. Found: C, 77.68, H, 6.39, N, 0.04. Step 2 Acetic acid 2-cyclopentyl, 4- (9-sea-2. 3-di g even-fried cake f 2. 3-b 1 -pan-4 -A) -Rudolate will contain 2-cyclopentyl-4-(2,3-dimethyl-naphthalenepyrene [2, 3-b]-) phen-4-ylphenyl ester (2.9 g, 7. 7 millimoles) in anhydrous dichloromethane (68 mL) was added ferric chloride (66 mg, 0.41 millimoles). Under nitrogen and cooled to _78 ° C. Avoid exposure to light and Anhydrous dichloromethane (11 ml) containing bromine (0.44 ml, 8.5 mmol) was added dropwise over 15 minutes. Stir for 45 minutes at -78 ° C, add dilute sodium sulfite to stop the reaction and pour to ice. Water (200 ml). Extract with ether (300 ml). Using water and brine, concentrated under reduced pressure and chromatographed with petroleum: ethyl acetate (95: 5), the title compound was obtained as a white solid (2.7 g, 79%): (CDC13): δ 8.28 ( d, 1H), 7.58-7.52 (m, 2H), 7.39 · 7 · 34 (m, 1Η), 7.29 (d, 1Η), 7.18 (dd, 1Η), 7.14 and 7.13 (d, 1Η ), 3.18 (quintet, 1Η), 2.44 (s, 3H), 2.40 (s, 3H), 2.06-2.02 (m, 2H), 1.75-1.45 (m containing a singlet at δ 1.60, 9H); MS (EI): [M +], 1 bromine isotope pattern, 492/494; Anal. Calc, for C27H25Br02S: C, 65.72, H, 5.11, N, 0.00. Found: C, 63.18, H, 4.96, N, 0.00. Step 3 2-cyclofluorenyl-4- (9-zhang-2. 3-Ershenmou-Sai_ "2. 3- hi-Kanpan-4-a phenol will contain 2-acetamyl-4- (2,3-Dimethyl-naphthalenepyrene [2, 3-b] -blazepan-4-yl) -phenyl ester (2.7 g, 5.4 mmol) tetrahydrofuran (88 ml) and methanol (30 ml), add KO 0Η-1 1 5- at room temperature. This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) (Please read the precautions on the back before filling this page) Order --------- line, staff consumption of Intellectual Property Bureau of the Ministry of Economic Affairs Cooperative printed 510900 A7 B7____ V. invention is described (" 4) solution (6 * 5 ml of 1 N solution, 65 mmol). After 1 to 5 hours, it was concentrated under reduced pressure. Combine with water (200 ml) and acidify with 10% HC1 to PH1. Extract with (Please read the precautions on the back before filling this page) Diethyl ether (300 ml). Wash the diethyl ether layer with water twice and then dry (sulfate pin). Concentrate under reduced pressure to obtain the white solid of the title compound ( 2.4 g, 100%): _SO-d6): δ 9.54 (s, 1Η), 8.16 (d, 1Η), 7.61 (m, 1Η), 7.52 (s, 1Η), 7.43 ( m, 1Η), 7.03 (s, 1Η), 6.93 (m, 2Η), 3.32 (m, 1Η), 2.41 (s, 3H), 1.94 (m, 2H), 1.58 (s, 3H), 1.72-1.42 (m, 6H); MS (EI): [M +], 1 bromine isotope pattern, 450/452; Anal · Calc · for C25H23BrOS: C, 66.52, H, 5.13, N, 0 · 00 · Found: C, 67.17, H, 5.25, N, 0.04. Step 4 (R) 4-U-(9 -bromo-2 · 3 -Second-Shen- 棼 _ 「2. 3-h 1-见盼- 4-a) -2-Evocarpus euphora Fructus sylvaticum succinimum succinica mimics 49 step 6 method, from 4- (9-bromo-2, 3-dimethyl-naphthalene hydrazone [2,3-b] -B Shupan-4 -yl) -2 -cyclopentylphenol (0.4 g, 0.89 mmol), (S) methyl 2-hydroxy-3-phenylpropionate (0.48 g , 2 · 7 mmoles), triphenylhydrazone (0.70 g, 2 · 7 mmoles), diethyl azodicarboxylate (0 · 4 2 ml, 2 · 7 Millimoles) and anhydrous benzene (6.0 ml), and reacted in an oil bath (85 ° C) for 4.5 hours to obtain a white solid (0.19 g, 34%): (DMS0-d6) : 8,17 (d, lH), 7.64-7.59 (βϊ, 1Η), 7.45-7.40 (βι, 2Η), 7.38-7.24 (ι, 5Η) 57.10-7.03 (m, 2H), 6β90-6 · 86 (ηι, 1Η), 5.28-5β24 (ιπ, 1Η), 3.70 and printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 3.6 (2 single lines, 3H, rotational isomers), 3.40 -3 · 24 (η, 3Η), 2.40 (s, 3H), 1.95-1 · 30 (π, 8Η), 1.49 (s, 3H); MS (EI): [Μ +], 1 Bromine isotope pattern, 6 1 2/6 1 4. Step 5 (R)-2-1 ~ 4-(9 -Zhang-2 · 3 -Dimethylditroph 骈 "2 · 3-b 1-见盼- 4-a) -2-Hydroxychloro 1-3: Benzoic acid-1 1 6- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 510900 Employees of Intellectual Property Bureau, Ministry of Economic Affairs Printed by Consumer Cooperative A7 B7 V. Description of Invention (M) (100 ml) Extraction. The extract was washed twice with water (100 ml), deconcentrated and decanted with petroleum ether: ethyl acetate (98: 2). Milling with petroleum ether gave the title compound as a white solid (1.2 g ， 5 2%): melting point 1 8 9 · 5 ～ 19 1 ° C; (DMSO-d6): S9.19 (s, lH), 8.18 (d, lH), 7.65- 7.61 (m, 1H), 7.50 -7.47 (m, 2H), 7.33 (d, 1H), 7.11 (d, 1H), 3.42 (quintet, 1H), 2.43 (s, 3H) f 2.00-1.97 (m, 2H), 1.69-1.46 (m , 6H), 1.60 (s, 3H); MS (E1): [M +], 2 bromine isotope pattern, 528 (46%), 530 (100%). 532 (52%): Ληιΐ, Calc, for C25H22Br20S: C, 56.62, H, 4.18, Ν, 0 · 00 · Found: C, 55.78, Η, 4.12, Ν, 0 · 05. Step 2 One Two—4 Two (9 -Chun-2 · Two Shenshi-Party_ & Di_1-8: Cyclops oxycarbo]] Dipprofen will contain 2-bromo-4- (9-bromo-2, 3-dimethyl-naphthalenepyrene [2,3 bu _ Pan-4 -yl) -2,6-cyclopentylphenol (1.2 g, 2.2 mmol), (S)-2-hydroxy-3-phenylpropanoic acid methyl ester (0.60 g, 3.3 Millimoles) and triphenyl (0 * 87 g, 3.3 millimoles) anhydrous benzene (20 ml), diethyl azodicarboxylate was added dropwise at room temperature under nitrogen. (0.5 2 ml, 3.3 mmol). After 5 hours at room temperature, it was attached to silica gel and chromatographed with petroleum ether: ethyl acetate (95: 5) to obtain the title compound. White solid (丨. 2 g, 86%): melting point 167 ~ 168 «5 ° C; NMR (CDC13): 8.28 (m? LH), 7.58-7.47 (m, 2H), 7.41-7.36 (ro, 2H) , 7.34-7 · 2 5 (, 5 Η), 7. 18 (1 Η), 5. 11 and 5 · 0 2 (didd, 1 H, rotamers), 3.66 and 3.6 3 (Two s, 3H, rotomer), 3.58- 3 · 3 3 U, 3 Η), 2 · 4 4 and 2. · 4 3 (two s, 3 Η, rotomer), 2, 2 0 (E, 1 Η), 1. 9 5 (κι, 1 Η), 1 · 7 5-1 · 3 2 (m with two single lines d 1 · 6 3 and 1 · 6 9 (rotomers), 9 Η); MS (EI): [Μ +], bromine isotope formula 1 1 8 A paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) (Please read the notes on the back before filling (This page) if ordered ------ |! Line * 510900 Printed by A7 B7, Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs V. Invention Description (Same, 6 90 (4 6%), 692 (100%), 694 (54%); Eight 11 & 1 * (^ 1 (! · F or C35H32Br203S: C, 60.70, Η, 4.66, Ν, 0.00.

Found : C，6 0 · 3 1，Η，4·6 4, Ν，0 · 0 1 0 步驟 3 f 2R) -2 -「2- 漳-4 - _( 9 「？…3 - h 1 -瞳盼-4 -某）-6 -瑗戊笨將含（2 R ) - 2 - [ 2 -溴-4 - ( 9 -溴-2，3 -二甲基-蔡駢 [2，3-b卜瞎盼-4-基）-6-璟戊苯氧基卜3-苯丙酸甲醋 (1·0克，〗·5毫莫耳）之四氫呋喃（30毫升）及甲醇 (10毫升），於室溫下滴加入^11溶液（3.〇毫升之1»溶液，3 · 0毫莫耳）。4小時後減壓濃縮。結合以水（1 0 0 毫升）及酸化以10%HC1。攪拌15分後過濾画體，以水：甲醇（95·· 5)洗。於真空及5G°C下乾燥18小時可得標題化合物之白色固體（〇·99克，100V) : 〇Pt· /1) = +3 8.44。（9· 6 24m g/mL，MeOH) ; NMR(DMS0-d6): <5 13·01(寬8，111)，8.19((1，111)，7.67-7.62(扭，11〇,7.54-7·22(ι»，9Η)，4·92(ιη，1Η)，3·46(Ηΐ，1Η)，3·34(Π!,2Η)，2·42 和 2 · 4 1 (二單線，3 Η ,旋轉異構物），1 · 9 9 ( ® , 1 Η )，1 · 9 8 (m，lH)，1·72-1·27(ηι 含二 s <Ϊ1·57 和 1·53(旋轉異構物），6H); MS(-ESI): [Μ-Η〗，2 溴同位素式樣，675(72%)Found: C, 6 0 · 3 1, Η, 4. 6 4, Ν, 0 · 0 1 0 Step 3 f 2R) -2-「2- Zhang-4-_ (9「?… 3-h 1- Hitomi-4 -a) -6-pentamidine will contain (2 R)-2-[2 -bromo-4-(9 -bromo-2,3 -dimethyl-Caijing [2,3-b Bublantan-4-yl) -6-pentaphenoxyb-methyl 3-phenylpropionate (1.0 g, 5 mmol) tetrahydrofuran (30 ml) and methanol (10 ml), A solution of ^ 11 (3.0 ml of 1 »solution, 3.0 mmol) was added dropwise at room temperature. After 4 hours, the solution was concentrated under reduced pressure. Water (100 ml) and acidified with 10% HC1. After stirring for 15 minutes, the painting was filtered, washed with water: methanol (95 ·· 5), and dried under vacuum at 5G ° C for 18 hours to obtain the title compound as a white solid (0.999 g, 100V): 〇Pt · / 1) = +3 8.44. (9.624 mg / mL, MeOH); NMR (DMS0-d6): < 5 13 · 01 (width 8,111), 8.19 ((1,111), 7.67-7.62 (Twist, 11, 7.54-7.22 (ι », 9Η), 4.92 (ιη, 1Η), 3.46 (Ηΐ, 1Η), 3.34 (Π !, 2Η), 2.42 and 2 · 4 1 (two single wires, 3 Η, rotational isomers), 1 · 9 9 (®, 1 Η), 1 · 9 8 (m, lH), 1.72-1 · 27 ( ηι containing two s < Ϊ1.57 and 1.53 (rotomers), 6H); MS (-ESI): [Μ-Η], 2 bromine isotope pattern, 675 (72%)

，6 7 7 ( 1 0 0 %), 6 7 9 ( 6 6 %) ; Anal . Calc . for C34H30Br 203S :C , 60 . 1 9 , H , 4 . 46 , Ν,0·00· Found : C , 5 9 . 5 3 , H ,4.35 s N , -0 . 04 . 例49 (R ) - 2 -「4 - ( 9 -淳-9 ▲ > 二申基二養駢[2 · 3 - h 1 -睹盼 -1 1 9 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線4^ (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7_ 五、發明說明（"Ο - 4 -某）-2 . β -二甲茱舊•某Ί - 3 -茱丙_ 步驟1 ( 2 -节某-4 , 5 -二申某-Bt im - 3 -某）-（4 -申氫某-3 , 5 -二甲茱某）-甲酮於含3，5 -二甲基-對~大茴香醇酸（1 5 . 2克，8 4 . 4毫莫耳，RH-21553-46-8)之無水二氯甲烷（200毫升），於室溫及氮氣下加入草醯氯（9. 6毫升，110毫莫耳）及 N，N -二甲基甲醯胺（5滴）。2小時後移除溶劑。於氮氣下溶於無水二、氯甲烷（2 0 0毫升加至2 , 3 -二甲基 -5 -竿瞎盼（1 7 · 1克，8 4 · 4毫莫耳）。冷卻至-7 8 °C並快速加入氯化錫（IV) ( 10 · 8毫升，92 · 8毫莫耳）。移除 -78°C浴，於室溫下攪拌2小時。倒至冰水中（1升），以***萃取（7 0 0毫升）後再以***華取（4 0 0毫升）。將***層以冰水（ 5 0 0毫升），稀釋重磺酸納（ 5 0 0毫升），水（5 D ϋ毫升），食鹽水（1升）洗，於硫酸鈉乾燥。減壓濃縮可製得標題化合物之黃色油（25 .2克，82%) ，NMR(DMS0-d6) : δ 7.40(s,2H),7.24-7.15(m,3H), 7.06(d,2H),3.83(s,2H),3.70(s,3H),2.26(s,6H),1.83 (s , 3H) 0 步驟2 4 - ( 2 , 3 -二甲某-若駢F 2 . 3 - b 1 -睹盼-4 -某） -2 , 6 -二甲酚於含（2 -苄基-4， 5 -二甲睹盼-3 -基）-(4 -甲氯基-3，5 -二, 6 7 7 (100%), 6 7 9 (66%); Anal. Calc. For C34H30Br 203S: C, 60. 1 9, H, 4. 46, Ν, 0 · 00 · Found: C , 5 9. 5 3, H, 4.35 s N, -0. 04. Example 49 (R)-2-"4-(9 -Chun-9 ▲ > Ershenji Eryang [2 · 3-h 1-见盼 -1 1 9-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) -------------------- Order- -------- Line 4 ^ (Please read the precautions on the back before filling out this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7_ 5. Description of the invention -2. Β -Dimethyljujube · MouΊ-3 -Jubing_ Step 1 (2 -jiemou-4, 5 -twoshenmou-Bt im-3 -some)-(4 -shenhydromou-3 , 5-Dimethoate)-ketone containing 3,5-dimethyl-p-anisinic acid (15.2 g, 8 4.4 mmol, RH-21553-46-8) Anhydrous dichloromethane (200 mL) was added at room temperature under nitrogen to chloramphicol (9.6 mL, 110 mmol) and N, N-dimethylformamide (5 drops). After 2 hours Remove the solvent. Dissolve in anhydrous dichloromethane (200 ml, add to 2, 3- Dimethyl-5-rods (17 · 1 g, 8 4 · 4 mmol). Cool to -7 8 ° C and quickly add tin (IV) chloride (10 · 8 ml, 92 · 8 MM). Remove the -78 ° C bath and stir at room temperature for 2 hours. Pour into ice water (1 liter), extract with ether (700 ml), and then take ether (400 ml). ). The ether layer was washed with ice water (500 ml), dilute sodium disulfonate (500 ml), water (5 D ϋ ml), brine (1 liter), and dried over sodium sulfate. Concentration gave the title compound as a yellow oil (25.2 g, 82%), NMR (DMS0-d6): δ 7.40 (s, 2H), 7.24-7.15 (m, 3H), 7.06 (d, 2H), 3.83 (s, 2H), 3.70 (s, 3H), 2.26 (s, 6H), 1.83 (s, 3H) 0 Step 2 4-(2, 3-dimethyl a-骈 F 2. 3-b 1 -Watchpan-4 -some) -2, 6-xylenol containing (2-benzyl-4, 5-dimethylforman-3)-(4-methylchloro-3,5 -di

甲苯基）-甲酮（25·2克，69·2毫莫耳）之無水二氯甲烷（420 毫升）置於氮氣及冷卻至-7 8 °C。於1 6分内滴加入三溴化硼 (2(K 9毫升，221毫莫耳），於78°C下攪拌1 . 5小時。移除-78°C -1 2 0 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） ------------0^--------訂---------線% (請先閱讀背面之注意事項再填寫本頁) 510900 經濟部智慧財產局員工消費合作社印製 A7 B7_______ 五、發明說明（Μ ) 浴，於室溫下攪拌4小時。倒至冰水中（1升）含亞硫酸氫鈉，以***萃取（1升）1次後再以***萃取（3 0 0毫升）。將*** 層以水（1 0 0 D毫升）洗2次，並以食鹽水（1 0 Q 0毫升）洗，於硫酸銷乾燥。減壓濃縮可得暗色殘渣，結合以第二次（2 -芾基 - 4 ， 5 - 二甲 9寒盼 - 3 - 基） - ( 4 - 甲氧基 - 3 ， 5 -二甲苯基）-甲酮（1 3 · 9克，3 8 · 1毫奠耳）及三溴化硼U 1 · 5毫升，1 2 2毫莫耳）。趿附至矽_，並層析以石油醚：乙酸乙酯（9 0 : 1 0 )可製得暗泡沫狀琥珀殘漬之2，6 -二甲基_ 4 - ( 2 , 3 -二甲基- 萘駢[2 , 3 - b ]-晴盼-4 -基卜酚（2 4 · 0 克，67%):_1?(0«30- d6): δ 8.41 (s, 2H), 7.93 (d, 1H), 7.49-7.39 (m, 2H), 7.34-7.28 (m, 1H), 6.87 (s, 2H), 2.38 (s, 3H), 2.23 (s, 6H), 1.62 (s, 3H); MS(EI): [M+] 332. 步驟3乙醱4二—L2—,—3二二甲基二養駢「2 , 3-b卜瞭盼莘、 -h 6 -二申茏酯將含4 - ( 2， 3 -二甲基-萘駢[2 , 3 - b卜P寒吩-4 -基）-2 ,6 -二甲酚（2 4 · 0克，7 2 . 2毫莫耳）之毗啶（2 0 0毫升），於（TC及氮氣下，於1 0分内滴加入乙酐（8 · 9毫升， 9 3 β 9毫莫耳）。於〇 °C下4 5分，置於冰箱1 8小時，移餘後於冰浴下攪拌2小時，回溫至室溫。倒至水（1升）並以1 (U H C 1酸化至Ρ Η 1。以***（1升）萃取，以1 〇 % fl c 1 (]升）洗，水（1升）洗2次，以食水（？00毫升）Tolyl) -methanone (25.2 g, 69.2 mmol) in anhydrous dichloromethane (420 ml) was placed under nitrogen and cooled to -78 ° C. Add boron tribromide (2 (K 9 ml, 221 mmol)) dropwise within 16 minutes, and stir at 78 ° C for 1.5 hours. Remove -78 ° C -1 2 0-This paper size applies China National Standard (CNS) A4 Specification (210 X 297 mm) ------------ 0 ^ -------- Order --------- Line% ( Please read the precautions on the back before filling out this page) 510900 Printed by A7 B7_______ of the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economy Contains sodium bisulfite, extracted once with ether (1 liter) and then with ether (300 ml). The ether layer was washed twice with water (100 D ml), and brine (1 0 Q 0 ml), washed with sulfuric acid pin, concentrated under reduced pressure to obtain a dark residue, combined with a second (2-fluorenyl-4, 5-dimethyl 9 Hanpan-3-)-(4-methoxy -3,5-xylyl) -methanone (13. 9 g, 38.1 mmol) and boron tribromide U 1.5 ml, 12 2 mmol). Attached to silica, and chromatographed with petroleum ether: ethyl acetate (90:10) to obtain a dark foamy amber residue of 2,6-dimethyl-4-(2, 3 -dimethyl) -Naphthyl naphthalene [2, 3-b] -Qingpan-4-kibuphenol (2 4 · 0 g, 67%): _ 1? (0 «30- d6): δ 8.41 (s, 2H), 7.93 (d, 1H), 7.49-7.39 (m, 2H), 7.34-7.28 (m, 1H), 6.87 (s, 2H), 2.38 (s, 3H), 2.23 (s, 6H), 1.62 (s, 3H ); MS (EI): [M +] 332. Step 3 Ethyl 4-di-L2 —, — 3-dimethyl-diisocyanate "2, 3-b dioxan, -h 6 -dishenyl ester Will contain 4-(2, 3-dimethyl-naphthalene hydrazine [2, 3-b p phenylene-4 -yl)-2, 6-xylenol (2 4 · 0 g, 7 2.2 Mol) of pyrimidine (200 ml), acetic anhydride (8.9 ml, 9 3 β 9 mmol) was added dropwise within 10 minutes under TC and nitrogen. 4 at 0 ° C 4 5 minutes, put in the refrigerator for 18 hours, and then stir in an ice bath for 2 hours, then warm to room temperature. Pour to water (1 liter) and acidify to 1 (UHC 1) with ether (1 Liter) extraction, washed with 10% fl c 1 (] liter), washed with water (1 liter) twice, with water (? 00 ml)

洗，再於硫酸鎂乾燥。減壓濃縮5並層析以石油醚：乙酸乙酯（97:3)可製得乳色固體（22。4克，79%) : NMR (CDC13): δ 8.26 (s，1H)，7.87 (d，1H), 7.58 (d，1H)，7.44-7.40 (m，1H)，7·33-7·29 (m, 1H), 7.07 (s, 2H), 2.42 (s, 3H), 2.41 (s, 3H), 2.23 (s, 6H), 1.67 (s, 3H); MS(EI): [M+] 374; Anal. Calc· for C24H2202S: C，76.97, H，5.92, N, 0·00· Found: C, 76.17, H, 5.75, N, 0.22. -121- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 510900 經濟部智慧財產局員工消費合作社印製 Α7 Β7 五、發明說明)Wash and dry over magnesium sulfate. Concentrated under reduced pressure 5 and chromatographed with petroleum ether: ethyl acetate (97: 3) to prepare a cream-colored solid (22.4 g, 79%): NMR (CDC13): δ 8.26 (s, 1H), 7.87 ( d, 1H), 7.58 (d, 1H), 7.44-7.40 (m, 1H), 7.33-7 · 29 (m, 1H), 7.07 (s, 2H), 2.42 (s, 3H), 2.41 ( s, 3H), 2.23 (s, 6H), 1.67 (s, 3H); MS (EI): [M +] 374; Anal. Calc · for C24H2202S: C, 76.97, H, 5.92, N, 0 · 00 · Found: C, 76.17, H, 5.75, N, 0.22. -121- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) -------------- ------ Order --------- line (please read the notes on the back before filling out this page) 510900 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs Α7 Β7 V. Description of the invention)

步驟4 乙—駿—4 -（ 9 -漳-2 . 3 '二兩某-赛駢「2 * 3 - bH ?分~^4'某）-2 . 6 -二申茱酯於含乙酸4 - ( 2，3 -二甲基-萘駢[2，3 - b卜B塞盼-4 -基） -2 > 6 -二甲苯酯（1 〇 s 〇克，2 6 · 7毫莫耳）及氯化鐵（〇 · 2 3 克，1…4毫莫耳）之無水二氯甲烷（2 3 1毫升）置於氮氣及冷卻至-7 8 °C ^.避免光照射下及於5 0分内滴加入含溴 (1·5毫升，2JK4毫莫耳）之無水二氯甲烷（38毫升）。3 0分後加入稀釋亞硫酸氫銷中止反應，稀釋以水後以 ***萃取。將***層以水洗2次，食鹽水後於硫酸鎂乾燥。減壓濃縮並層析以石油醚：乙酸乙酯（9 7 : 3)可製得標題化合物之白色固體（6 · 7克，S 5 !〇，（ D M S 0 - d 6 ) : (Ϊ 8.27 (d, 1H), 7.60 (d, 1H), 7.56-7.52 (ddd, 1H), 7.38-7.34 (ddd, 1H), 7.06 (s, 2H), 2.43 (s, 3H), 2.41 (s, 3H), 2.22 (s, 6H), 1.64 (s, 3H); MS(EI): [M+], 1 溴同位素式樣，452/454; Anal. Calc. forC24H21Br02S: C, 63.58, H，4·67, Ν，0·00· Found: C, 63.41, H, 4.45, N, 0.08. 步驟δ 4 - ( 9 -漳-2 · 3 -二申基-棻駢f 2 . 3 - h Ί -睹盼- 4 - 基）‘ fi -二申酚將含乙酸4-(9-漠-2，3-二甲基-蔡駢[2，3-b】-瞎盼- 4-基）-2，β-二甲苯酯（6 · 5克，14 · 3毫莫耳）之四氫呋喃（ 2 4 0毫升）及甲_ ( 8 G毫升），於室溫下滴加入Κ 0 Η溶液（1 2毫升之 1Ν溶液，〗7 *2毫莫耳）。於室溫下4小時後置於冰箱18小時。移除後於室溫下攪拌。加入K0 Η溶液（41 · 5毫升之1N溶液，41 . 5 毫莫耳），四氫呋喃（50毫升）及甲醇（10毫升）。稀釋以水（wo 毫升），酸化以1 N H C 1後以***萃取。將***層以水（5 〇〇毫升）洗2次，後於硫酸纟ϋ乾燥。減壓濃縮可得殘渣，吸附至矽膠。 -122- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） -----------Φ--------訂---------線% (請先閱讀背面之注意事項再填寫本頁) 510900 A7 B7 五、發明說明（) 層析以石油醚·.乙酸乙酯（9 7 : 3，9 5 : 5 )可製得標題化合物之白色泡沫狀固體（5.5 克，93%):NMR(CDC13): <Ϊ8·41(8，1Η)，8·16 (請先閱讀背面之注意事項再填寫本頁) (d, 1H), 7.64-7.54 (m, 2H), 7.46-7.40 (m, 1H), 6.89 (s, 2H), 2.41 (s, 3H), 2.23 (s, 6H), 1.60 (s, 3H); MS(-ESI): [M-H],溴同位素式樣，4 0 9 / 4 1 1。步驟 β ( 2R) - ? -「4 - ( 9 -漳-?…3 -二甲基—_養胤[2、3 - b 1 -睹盼-4 -某）-2 , ft -二甲茱氤基1 - 3 _苯_丙—酸甲酷將含4-(9 -溴-2，3_二甲基-蔡®[2，3_b]_嘑盼-4-基） -2 , 6 -二甲酚（5 . 0克，1 2 «1毫莫耳），（S ) - 2 -羥基-3 -苯丙酸甲酯（3.3克，18·3毫莫耳），及三苯瞵（4·8克，18·3毫莫耳）之無水苯（50毫升），於室溫及氮氣下，於25分内滴加入偶氮二羧酸二乙酯（2 · 6毫升，1 8 · 3毫莫耳）。加熱 2小時，於室溫下攪拌3天。吸附至矽_並以石油醚：乙酸乙酯（9 5 : 5 )層析2次可製得白色泡沫狀固體（4 . 5克， 65%): NMR (DMSO-d6): δ 8.18 (d, 1H), 7.64 (ddd, 1H), 7.53-7.43 (m, 2H), 7.38- 7.24 (m, 5H), 7.00 (s, 2H), 4.80 (t, 1H), 3.58 (s, 3H), 3.31 (m, 2H), 2.42 (s, 3H), 2.24 (s, 3H), 2.19 (s, 3H), 1.55 (s, 3H); MS(EI): [M+], 1 溴同位素式樣， 572/574; Anal. Calc, for C32H29Br03S: C, 67.01, H, 5.10, N, 0.00. Found: C, fi 6 . 3 3 , H，5 . 0 9，N，0 · 0 9 ; A n a 1 y t i c a 1 Η P L C 顯示主成分 (9 4 . 3 9 % ) 0 步驟 7 ( 2 R > - 2 -「4 - ( 9 -溴-2 · 3 '二甲某-棻駢「2 . 3 - b 1 經濟部智慧財產局員工消費合作社印製 -BfB分-4-某）-2. 6-二甲茱氬某1 - 3-茱丙酴將含（21?_)-卜[4-(9-溴-2，3-二甲基-萘駢[2，3-1)】 -瞎吩-4-基）-2，6-二甲苯氧基]-3-苯丙酸甲酯（3 · 1 克，5. 4毫莫耳）之四氫呋喃（125毫升）及甲醇（41毫升），於室猻下滴加入K0H溶液（6· 5毫升之1N溶液，6.5 -1 2 3 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） W0900 A7 ^---------B7_ 五、發明說明毫荑耳）〇於室溫下1 β 5小時後置於冰箱1 8小時。自冰箱移除後於室溫下攪拌。加入Κ0Η溶液（19 .5毫升之1Ν 溶液，1 9 · 5毫莫耳），於室溫下攪拌9 . 5小時。減壓濃 _，將所得殘渣以水（1升）稀釋將水層酸化以濃· 酸至PH1。以***（700毫升）萃取。將***層以水（500 毫升）洗2次，後於硫酸鈉乾燥。減壓濃縮，以矽膠柱層析（處理以2 %磷酸在甲醇），溶離以石油醚：乙酸乙酯=9 G : 1 0，8 6 : 1 4 )可製得標題化合物之白色泡沫狀固體 U · 9克，6 4%) : Opt· Rot· [a]25/D = +33.38。（10.035 mg/mL, MeOH); NMR(DMSO-d6): δ 12.90 (broad singlet, 1H), 8.17 (d, 1H), 7.63 (ddd, 1H), 7.50-7.43 (m, 2H), 7.36-7.23 (m, 5H), 6.97 (s, 2H), 4.71 (t, 1H), 3.25 (d, 2H), 2.41 (s, 3H), 2·24 (s，3H)，2·21 (s，3H), 1·54 (s, 3H); MS(EI): [M+], 1 溴同位素式樣，558/560; Anal· Calc, for C31H27Br03S: C，66.55, Η, 4·86, N, 0·00· Found: C, 65.91, Η, 5Ό5, N, 0.09;顯示主成分（9 9 · 5 % )。例5n (η -2-「4- (2. 二甲某-赛駢「2· 3- bl-睹盼-4 '基—)_ -2 . ft -二惡丙茱氩某1 - 3 -荣丙酶步驟1 ( 2 -苄某-4 · 5 -二申某-睐盼-3 -基）-（3 , 5—-—二— 丙某-4-甲氳茱某）-申酗仿例49步驟1之方法，由3，5-二異丙基-對-大舖香醇酸（5.0克，21·2毫莫耳，RN-117439-59-5)，草醯氯 (2.2毫升，25.4毫莫耳），51,{}-二甲基甲醯胺（2滴） ,2，3 -二甲基-5 -苄睹盼（4 · 3克，2 1 · 2毫莫耳），氯化錫（I V ) ( 5 · 0毫升，4 2 · 7毫莫耳），及無水二氯甲烷（82毫升），可製得標題化合物之黃油（4.1克，45¾): -1 2 4 - 本紙張尺度適用中國國家標準（CNS)A4規格(210>< 297公釐) (請先閱讀背面之注意事項再填寫本頁) έ 訂---------線·· 經濟部智慧財產局員工消費合作社印製 510900 A7 B7___ 五、發明說明（、—） NMR(DMSO-d6): δ 7.47 (s，2H)，7.23-7.12 (m，3H)，7.02-6.99 (m，2H), 3·86 (s, 2H), 3.73 (s, 3H), 3.31-3.20 (m, 2H), 2.27 (s, 3H), 1.82 (s, 3H), 1.15 (d, 12H); MS(EI): [M+] 420. (請先閱讀背面之注意事項再填寫本頁) 步驟 2 —6-二爨丙某-4- ( 2 . 3'二 _ 簇 _. 3-hl- 睹盼-4-某）-酚彷例49步驟2之方法，由（2-苄基-4，5-二甲基-瞎盼-3 -基）-(3 , 5 -二異丙基-4 -甲氣苯基卜甲醒1 ( 4 . 3克，1 0 · 1毫莫耳），三溴化硼（3 · 1毫升，3 2 · 4毫莫耳），及二氯甲烷（6 0毫升），可製得檫題化合物之黃色泡沫（1.2克，30%):“卩（0!^0-d6): 5 8.42 (s, 1H), 8.24 (s, 1H), 7.94 (d, 1H), 7.48-7.32 (m, 3H), 6.90 (s, 2H), 3.45-3.35 (m, 2H), 2.38 (s, 3H), 1.57 (s, 3H), 1.15 (d, 12H); MS(-ESI): [M-H] 387. 步驟 3 (2ΙΠ 3-二申甚-棻駢「2. lhl-臃盼-4 -某）-2. -二異丙某茏氳某1-3 -茱丙酴申酯Step 4 B—Jun—4-(9-Zhang-2. 3'-two-two-some-saiyan "2 * 3-bH? Cent ~ ^ 4 'some)-2. 6-dishenyl ester in acetic acid 4 -(2,3-dimethyl-naphthalenepyrene [2,3 -b-B-Seppan-4 -yl) -2 > 6-xylyl ester (10 s g, 2 6 · 7 mmoles ) And ferric chloride (0.23 g, 1 ... 4 mmol) anhydrous dichloromethane (23 1 ml) under nitrogen and cooled to -7 8 ° C ^. Avoid exposure to light and at 5 Anhydrous dichloromethane (38 ml) containing bromine (1.5 ml, 2 JK 4 mmol) was added dropwise within 0 minutes. After 30 minutes, the reaction was stopped by adding dilute hydrogen sulfite, diluted with water and extracted with ether. The ether layer was washed twice with water, brine, and dried over magnesium sulfate. It was concentrated under reduced pressure and chromatographed with petroleum ether: ethyl acetate (9 7: 3) to obtain the title compound as a white solid (6.7 g, S 5 ! 〇, (DMS 0-d 6): (Ϊ 8.27 (d, 1H), 7.60 (d, 1H), 7.56-7.52 (ddd, 1H), 7.38-7.34 (ddd, 1H), 7.06 (s, 2H ), 2.43 (s, 3H), 2.41 (s, 3H), 2.22 (s, 6H), 1.64 (s, 3H); MS (EI): [M +], 1 bromine isotope pattern, 452/454; Anal. Calc. ForC24H21Br02S: C, 63 .58, H, 4.67, Ν, 0.00. Found: C, 63.41, H, 4.45, N, 0.08. Step δ 4-(9-张 -2 · 3-二申基-棻骈 f 2 . 3-h Ί-睹盼-4 -yl) 'fi-Dishenol will contain acetic acid 4- (9- Mo-2,3-dimethyl-Cai 骈 [2,3-b] -blind- 4-yl) -2, β-xylyl ester (6.5 g, 14.3 mmol) tetrahydrofuran (240 ml) and formazan (8 G ml) were added dropwise at room temperature Rhenium solution (12 ml of 1N solution, 7 * 2 millimoles). After 4 hours at room temperature, place in the refrigerator for 18 hours. Remove and stir at room temperature. Add K0 Rhenium solution (41 · 5 ml) 1N solution, 41.5 mmol), tetrahydrofuran (50 ml) and methanol (10 ml). Dilute with water (wo ml), acidify with 1 NHC 1 and extract with ether. Extract the ether layer with water (50. 〇mL) Washed twice, and then dried in osmium sulfate. The residue can be obtained by concentration under reduced pressure and adsorbed to the silica gel. -122- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) --- -------- Φ -------- Order --------- Line% (Please read the notes on the back before filling this page) 510900 A7 B 7. V. Description of the invention () Chromatography with petroleum ether · ethyl acetate (9 7: 3, 9 5: 5) can prepare the title compound as a white foamy solid (5.5 g, 93%): NMR (CDC13) : < Ϊ8 · 41 (8,1Η), 8 · 16 (Please read the notes on the back before filling in this page) (d, 1H), 7.64-7.54 (m, 2H), 7.46-7.40 (m, 1H ), 6.89 (s, 2H), 2.41 (s, 3H), 2.23 (s, 6H), 1.60 (s, 3H); MS (-ESI): [MH], bromine isotope pattern, 4 0 9/4 1 1. Step β (2R)-?-"4-(9 -Zhang-? ... 3 -Dimethyl — 胤养胤 [2,3-b 1-睹盼 -4-某) -2, ft-Dimethoate Fluorenyl 1-3 _benzene_propane-methyl acetophenate will contain 4- (9 -bromo-2,3_dimethyl-Cai® [2,3_b] _fluorene-4-yl) -2, 6- Xylenol (5.0 g, 1 2 «1 mmol), (S)-2-hydroxy-3 -phenylpropionate methyl ester (3.3 g, 18.3 mmol), and triphenylhydrazone ( 4.8 g, 18.3 mmol) of anhydrous benzene (50 ml), and diethyl azodicarboxylate (2. 6 ml, 1 8 · 3 millimoles). Heated for 2 hours and stirred at room temperature for 3 days. Adsorbed to silica and chromatographed twice with petroleum ether: ethyl acetate (95: 5) to obtain a white foamy solid (4. 5 g, 65%): NMR (DMSO-d6): δ 8.18 (d, 1H), 7.64 (ddd, 1H), 7.53-7.43 (m, 2H), 7.38- 7.24 (m, 5H), 7.00 (s , 2H), 4.80 (t, 1H), 3.58 (s, 3H), 3.31 (m, 2H), 2.42 (s, 3H), 2.24 (s, 3H), 2.19 (s, 3H), 1.55 (s, 3H); MS (EI): [M +], 1 bromine isotope pattern, 572/574; Anal. Calc, for C32H29Br03S: C, 67.01, H, 5.10, N, 0.00. Found: C, fi 6. 3 3, H 5. 0 9, N, 0 · 0 9; Ana 1 ytica 1 Η PLC shows the main component (9 4. 3 9%) 0 Step 7 (2 R >-2-"4-(9 -Bromo-2 · 3 'Dijiamou- 棻骈「2. 3-b 1 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs-BfB points-4-a） -2. 6-Dimethazone argon 1-3-Zhubing酴 will contain (21? _)-Bu [4- (9-bromo-2,3-dimethyl-naphthalene 骈 [2,3-1)] -blphen-4-yl) -2,6-di Toluyloxy] -3-phenylpropanoic acid methyl ester (3.1 g, 5.4 mmol) in tetrahydrofuran (125 ml) and methanol (41 ml), K0H solution (6.5 1N solution in milliliter, 6.5 -1 2 3-This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) W0900 A7 ^ --------- B7_ V. Description of the invention ) 0 1 hour at room temperature for 5 hours and then put in the refrigerator for 18 hours. Remove from the freezer and stir at room temperature. K0Η solution (19.5 ml of a 1N solution, 19.5 mmol) was added and stirred at room temperature for 9.5 hours. The solution was concentrated under reduced pressure, and the obtained residue was diluted with water (1 liter), and the aqueous layer was acidified to be concentrated and acidified to pH1. Extract with ether (700 mL). The ether layer was washed twice with water (500 ml) and dried over sodium sulfate. Concentrated under reduced pressure, and subjected to silica gel column chromatography (treated with 2% phosphoric acid in methanol), and dissolved with petroleum ether: ethyl acetate = 9 G: 1 0, 8 6: 1 4) to obtain the title compound as a white foamy solid. U · 9g, 64%): Opt · Rot · [a] 25 / D = +33.38. (10.035 mg / mL, MeOH); NMR (DMSO-d6): δ 12.90 (broad singlet, 1H), 8.17 (d, 1H), 7.63 (ddd, 1H), 7.50-7.43 (m, 2H), 7.36- 7.23 (m, 5H), 6.97 (s, 2H), 4.71 (t, 1H), 3.25 (d, 2H), 2.41 (s, 3H), 2.24 (s, 3H), 2.21 (s, 3H), 1.54 (s, 3H); MS (EI): [M +], 1 bromine isotope pattern, 558/560; Anal · Calc, for C31H27Br03S: C, 66.55, Η, 4.86, N, 0 · 00 · Found: C, 65.91, Η, 5Ό5, N, 0.09; the main component is displayed (9 9 · 5%). Example 5n (η -2- "4- (2. Dimethyl a-Saiyan" 2 · 3- bl- Kanpan-4 '-based-) _-2. Ft-Dioxolium argon 1-3- Ranse step 1 (2 -benzyl-4-5 -di Shenmou -Lanpan-3 -yl)-(3, 5---two-Bingmou-4 rutaeum)-Shen Jiimi Example 49 The method of step 1 consists of 3,5-diisopropyl-p-dapoline alkyd acid (5.0 g, 21.2 mmol, RN-117439-59-5), chloramphenicol (2.2 ml, 25.4 millimoles), 51, {}-dimethylformamide (2 drops), 2,3-dimethyl-5 -benzylamine (4.3 grams, 21.2 millimoles), Tin (IV) chloride (5.0 ml, 4 2 · 7 mmol) and anhydrous dichloromethane (82 ml), the title compound butter (4.1 g, 45¾) can be prepared: -1 2 4- This paper size applies to China National Standard (CNS) A4 specifications (210 > < 297 mm) (Please read the precautions on the back before filling this page) Printed by the Intellectual Property Bureau's Consumer Cooperatives 510900 A7 B7___ V. Invention Description (,-) NMR (DMSO-d6): δ 7.47 (s, 2H), 7.23-7.12 (m, 3H), 7.02-6.99 (m, 2H) ), 3.86 (s, 2H), 3.73 (s, 3H), 3. 31-3.20 (m, 2H), 2.27 (s, 3H), 1.82 (s, 3H), 1.15 (d, 12H); MS (EI): [M +] 420. (Please read the precautions on the back before filling (This page) Step 2 —6-Dioxopropyl-4- (2. 3'bis_cluster_. 3-hl- Jianpan-4-some) -phenol Example 49 Step 2 method, from (2- Benzyl-4,5-dimethyl-benzyl-3 -yl)-(3,5-diisopropyl-4-methylphenylphenylcarbamidine 1 (4.3 g, 10 · 1 mmol) ), Boron tribromide (3.1 ml, 3.2 ml) and dichloromethane (60 ml), a yellow foam (1.2 g, 30%) of the title compound can be prepared: "卩(0! ^ 0-d6): 5 8.42 (s, 1H), 8.24 (s, 1H), 7.94 (d, 1H), 7.48-7.32 (m, 3H), 6.90 (s, 2H), 3.45-3.35 (m, 2H), 2.38 (s, 3H), 1.57 (s, 3H), 1.15 (d, 12H); MS (-ESI): [MH] 387. Step 3 (2ΙΠ 3- 二申甚-棻骈「2. lhl- 臃望 -4 -a） -2.

仿例4 9步驟6之方法，由4 - ( 2，3 -二甲基-萘駢[2，3 - b ] -瞎吩-4-基）-2-異丙酚（fl · 33克，0 · 84毫莫耳），（S) -2_羥基-3-苯丙酸甲酯（1·5克，8·3毫奠耳），三苯膦 (2.2克，8 .3毫莫耳），偶氮二羧酸二乙酯（1.3毫升， 8.3毫莫耳）及無水苯（9.0毫升），於油浴（85°〇)下 1 8小時可製得標題化合物之油（0 · 1 1克，2 4 % ) : N M R (DMS0~dG) : δ 8.4 5 (s,lH)?7.96(d,lH),7,50-7. 25(βι, 經濟部智慧財產局員工消費合作社印製 8H) ，7,03(s，2H)，4.54(t，lH)，3.56(s，3Η)，3.40-3·18(班， 4 Η ) , 2 . 3 8 ( s，3 Η )，1 · 5 1 ( s，3 Η )，1 · 1 4 和 1 · 1 3 (二雙線，6 Η，旋轉異構物），1 · 07和1 .04 (二雙線，6Η力旋轉異構物）； MS(EI): [ιη+]550〇步驟 4 ( 2R ) -2-U- (2· 3-二申某-養駢」2 , 3 -bl - _ -125- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 B7The method of Step 4 9 of Example 4 was carried out from 4- (2,3-dimethyl-naphthalenepyrene [2,3-b] -blphen-4-yl) -2-propofol (fl · 33 g, 0.84 mol), methyl (S) -2-hydroxy-3-phenylpropionate (1.5 g, 8.3 mol), triphenylphosphine (2.2 g, 8.3 mol) ), Diethyl azodicarboxylate (1.3 ml, 8.3 mmol) and anhydrous benzene (9.0 ml) in an oil bath (85 ° 〇) for 18 hours to obtain the title compound as an oil (0.11 1 g, 24%): NMR (DMS0 ~ dG): δ 8.4 5 (s, lH)? 7.96 (d, lH), 7,50-7. 25 (βι, printed by the employee's consumer cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs System 8H), 7,03 (s, 2H), 4.54 (t, 1H), 3.56 (s, 3Η), 3.40-3 · 18 (ban, 4Η), 2. 3 8 (s, 3Η), 1 · 5 1 (s, 3 Η), 1 · 1 4 and 1 · 1 3 (two double lines, 6 Η, rotational isomers), 1 · 07 and 1.04 (two double lines, 6 Η rotational rotations) Structure); MS (EI): [ιη +] 550〇 Step 4 (2R) -2-U- (2.3 · Second-Shen Mou-Liang 骈 ”2, 3 -bl-_ -125- Paper size Applicable to China National Standard (CNS) A4 (210 X 297 mm) 510900 A7 B7

經濟部智慧財產局員工消費合作社印製五、發明說明（lH：) B分-4 -某）-2 · 6 -二累丙某笨氯基1二3 -苯丙酸彷例4 9步驟7之方法，由（2 R ) - 2 - [ 4 - ( 2，3 -二甲基-萘駢丨2, 3-b] -瞎盼-4-基）-2，6 -二異丙基苯氯基卜3 -苯丙酸甲釀（(Kll克，〇·2毫莫耳），Κ0Η溶液（0.39毫升之1N溶液，0.39毫莫耳），四氫呋喃（3毫升），及甲醇（1毫升）可製得標題化合物之白色固體（〇· 克，98%0:1^1^0“0- d6)： δ 12.97 (broad s, 1H), 8.46 (s, 1H), 7.96 (d, 1H), 7.47-7.25 (m, 8H), 7.04 (s,Printed by the Employees' Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. 5. Description of the invention (lH :) B points -4--)-2-6-Dilecyl 1-chloro 3- 12-phenylpropionic acid 4 4 Method by (2 R)-2-[4-(2,3 -dimethyl-naphthalene 骈 2, 3-b] -blaze-4-yl) -2,6 -diisopropylbenzene Chlorobutane 3-phenylpropionate (Kll, 0.2 mmol), K0Η solution (0.39 ml of 1N solution, 0.39 mmol), tetrahydrofuran (3 ml), and methanol (1 ml) The title compound was obtained as a white solid (0.0 g, 98% 0: 1 ^ 1 ^ 0 "0-d6): δ 12.97 (broad s, 1H), 8.46 (s, 1H), 7.96 (d, 1H) , 7.47-7.25 (m, 8H), 7.04 (s,

2H), 4.47 (t, 1H), 3.41-3.30 (m, 2H), 3.28-3.23 (m, 2H), 2.40 (s, 3H), 1.53 (s, 3H), 1.15 (d, 6H), 1.08 (d, 6H); MS(EI): [M+] 536; Anal. Calc, for C35H3603S: C, 78.32, Ht 6.76, N, 0.00. Found: C, 77.12, H, 6.86, N, -0.11; Analytical HPLC 顯示主成分（9 3 · 2 % ) 例51 J R) -2-「4-(2, 3 -二申某-惹謝「2. 3-b1-_ 盼-[某）贏荣氣基1-3-笨丙酸步驟1 (: 2-苄基-4，5-二甲基盼-3-基）-(3-氟- 4- 申氬茏某> -_ _ 仿例49步驟1之方法，由3-氟-對-大_番醇酸（10.0 克，58· 8毫莫耳），草醯氯（6· 2毫升，71 .04毫莫耳），N，卜二甲基甲醯胺（12滴），2，3-二甲基-5-苄B寒盼（1 1 · 9克，58 · 8毫莫耳），氯化錫（I V) (10·3毫升，88.0毫莫耳），及無水二氯甲烷（130毫升），可製得標題化合物之黃色固體（7·53克，68%):MS(+ESI):[M+H]355;2H), 4.47 (t, 1H), 3.41-3.30 (m, 2H), 3.28-3.23 (m, 2H), 2.40 (s, 3H), 1.53 (s, 3H), 1.15 (d, 6H), 1.08 (d, 6H); MS (EI): [M +] 536; Anal. Calc, for C35H3603S: C, 78.32, Ht 6.76, N, 0.00. Found: C, 77.12, H, 6.86, N, -0.11; Analytical HPLC showed the main components (9 3 · 2%) Example 51 JR) -2- "4- (2, 3-two Shenmou-Ya Xie" 2. 3-b1-_ hope-[some] Win Rong gas base 1 -3-benzylpropanoic acid Step 1 (: 2-benzyl-4,5-dimethylpan-3-yl)-(3-fluoro-4 4-sulfonium) > -_ _ Example 49 Step 1 The method consists of 3-fluoro-p-glyoxylic acid (10.0 g, 58.8 mmol), chloramphenicol (6.2 ml, 71.04 mmol), N, dimethyl Formamidine (12 drops), 2,3-dimethyl-5-benzyl B Hanpan (11. 9 g, 58.8 mmol), tin (IV) chloride (10.3 ml, 88.0 Millimolar), and anhydrous dichloromethane (130 ml), the title compound was obtained as a yellow solid (7.53 g, 68%): MS (+ ESI): [M + H] 355;

Anal. Calc, for C21H19F02S: C, 71.16, H, 5.40, N, 0.00. Found: C, 70.01, H, 5.43, N, -0.06. 步驟2 2-氩-4-（ 2 . 2-二申着iLL2 , 3-b卜瞎盼-4-某）Anal. Calc, for C21H19F02S: C, 71.16, H, 5.40, N, 0.00. Found: C, 70.01, H, 5.43, N, -0.06. Step 2 2-Arg-4- (2.2. iLL2, 3-b Bu blind hope -4-))

:_1L -1 2 6 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 510900 經濟部智慧財產局員工消費合作社印製 A7 B7 五、發明說明（κ) 仿例49步驟2之方法，由（2-苄基-4，5-二甲基一瞎盼 -3-基）_(3〜氟-4-甲氣苯基）-甲國（7·5克，21.2毫莫耳），三溴化硼（7.0毫升，74.3毫莫耳），及二氯甲烷（88毫升），可製得標題化合物之黃色泡沫（6β7克 599%): MS(Ei). [m+]322; Anal. Calc, for C20H15F0S ：C, 74.51, h,4.89, Ν,Ο.ΟΟ. Found: C,73.96, H，4,94，步驟 3 —(—2 i i - 2 - F 4 - ( 9 -漳-2、3 -二申某-棻 if f ?…t h 1 二建1 - 4 -某）-2 -蘊-茱氬某1-3-¾丙醣仿例49步驟6之方法，由2-氟-4- (2，3-二甲基-萘駢 [2，3 - b卜8寒吩-4 -基）-酚（1 · fl克，3 · 1毫奠耳），(S) -2-羥基-3-苯丙酸甲酯（0.67克，3.7毫莫耳），三苯瞵（〇。98克，3.7毫莫耳），偶氮二羧酸二乙酯（〇.59毫升，3.7毫莫耳）及無水苯（20毫升），於油浴（85°C ) 下5小時可製得標題化合物之白色固體（0· 86克），其可不經純化而使用。仿例49步驟7之方法，由（2R)-2-[4-(9-溴-2，3-二甲基-萘駢[2, 3-b卜B塞盼-4-基卜2-氟-苯氣基]-3-苯丙酸: _1L -1 2 6-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) -------------------- Order --- ------ line (Please read the notes on the back before filling this page) 510900 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (κ) The method of step 2 of Example 49 is provided by ( 2-benzyl-4,5-dimethyl-monobenzyl-3-yl) _ (3 ~ fluoro-4-methylphenyl) -methylamine (7.5 g, 21.2 mmol), tribromo Boron (7.0 ml, 74.3 mmol) and dichloromethane (88 ml) were used to prepare the title compound as a yellow foam (6β7 g 599.9%): MS (Ei). [M +] 322; Anal. Calc, for C20H15F0S: C, 74.51, h, 4.89, Ν, Ο.ΟΟ. Found: C, 73.96, H, 4,94, Step 3 — (— 2 ii-2-F 4-(9 -zhang-2,3 -Er Shenmou-棻 if f? ... th 1 Erjian 1-4 -mum) -2-Yun-Zhu Ar 1-3-3-¾ triose analogue 49 step 6 method, from 2-fluoro-4- (2,3-dimethyl-naphthalenepyrene [2,3 -b 8-hydroxyphen-4 -yl) -phenol (1.1 fl g, 3.1 mmol), (S) -2-hydroxy- Methyl 3-phenylpropionate (0.67 g, 3.7 mmol), triphenylhydrazone (0.98 g 3.7 millimoles), diethyl azodicarboxylate (0.59 milliliters, 3.7 millimoles) and anhydrous benzene (20 milliliters) in an oil bath (85 ° C) for 5 hours to obtain the title compound. White solid (0.86 g), which can be used without purification. The method of step 7 of Example 49 was followed by (2R) -2- [4- (9-bromo-2,3-dimethyl-naphthalene} [ 2,3-b-B-B-Seppan-4-yl-b-fluoro-phenylamino] -3-phenylpropanoic acid

甲酯（〇·86克，1.8毫莫耳），Κ0Η溶液（3.6毫升之1N溶液，3β6毫莫耳），四氫呋喃（12毫升），及甲醇（4毫升）可製得標題化合物之白色固體（0 · 4 1克，6 3 % : 0 p t · R 〇 t · [ a ] 2 5 / D =+0.87° (11.473 mg/mL, MeOH); MS(EI): [M+] 470; Anal. Calc, for C29H23F03S: C, 74.02, H, 4.93, N, 0.00. Found: C, 73.95, H, 5.22, N, 0.12. -127- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) -· I n mmMme n I in I 一 ον ϋ ϋ 線· 510900 A7 B7_ 五、發明說明) 例52 (R) -2-ί4-(9 -溴-2. 3-二申基-赛駢『2. 3-bl-_ 盼 (請先閱讀背面之注意事項再填寫本頁) -4 -某）-2 -氬-茱Μ某P 3 - 丙醵步驟 1 : Ζ _ 2 -氟-4 - ( 9 -淳-2 , 3 -二申某-赛酣「2 > 3 - b 1 -嗦盼“ 4 -基)__-苯醋仿例4 9步驟3之方法，由2 -氟-4 - ( 2，3 -二甲基-萘駢 ί 2，3 - b】-睹盼-4 -基）-酚（1克，3 · 1毫莫耳），乙酐 (0.36毫升，3.8毫莫耳），及毗啶（7.5毫升）可製得黃色固體（1 克），其可不經純化而使用。仿例4 9步驟4之方法，由乙酸2-氟-4- ( 2，3-二甲基-萘駢[2 , 3-b ] -瞎盼-4 -基）-苯酯（1 · 1克，2 · 9毫莫耳），氯化鐵 (2 4 · 8毫克，G · 1 5毫莫耳），溴（（3 · 1 6毫升，3 · 2毫莫耳）及二氯甲烷（1 2毫升）可製得標題化合物之黃油 (0 · 8 6 克，6 7 % ) : M S ( E I ) : [ Μ + ]，溴同位素式樣 4 4 2 / 4 4 4 0 步驟2 : 2 -氩-4 - ( 9 -海-2 < 3 -二甲某-赛g游「2 . 3 - b 1 -睹盼-4 -基)_____-酣仿例4 9步驟5之方法，由乙酸2 -氟-4 - ( 9 -溴-2 , 3 -二經濟部智慧財產局員工消費合作社印製甲基-萘駢[2，寒吩-4-基）-苯酯（0·29克，0.65 毫莫耳），Κ0Η溶液（（Κ79毫升之1Ν溶液，G.79毫莫耳），四氫呋喃（12毫升），及甲醇（7·5毫升）可製得標題化合物之摻白色固體（〇 · 3克，1 0 0 Γ) : M S ( Ε I ) : [ Μ + ] ，1溴同位素式樣，4 0 0 / 4 fl 2。步驟 3 : ( R ) - 2 -氩-「4 - ( 9 -漳-2 > 3 -二申某-養駢 f 2 . 3 - b 1 - -12 8- 本紙張尺度適用中國國家標準（CNS)A4規格（210 χ 297公釐）經濟部智慧財產局員工消費合作社印製 510900 A7 B7_ 五、發明說明（、β) 睹盼-4 -某）-2-氩茱氩某1-3-茱丙酴申_ 仿例4 9步驟fi之方法，由2 -氟-4 - ( 9 -溴-2，3 -二甲基 -萘駢[2，3 - b卜B寒盼-4 -基）-酚（0 · 2 9克，0 · 7 2毫莫耳），（S ) - 2 -羥基-3 -苯丙酸甲酯（0 · 1 9克，1 · 1毫莫耳） ,三苯瞵（0 · 2 8克，1 · 1毫莫耳），偶氮二羧酸二乙酯 (0.17毫升，1」毫莫耳）及無水苯（5·0毫升），可製得標題化合物之白色固體（〇·23克，58%) ·· MS(EI): [Μ + ]，1溴同位素式樣，5 6 2 / 5 6 4。步驟 4 : ( R ) - 2 -氩-「4 - ( 9 -海-2 · 3 -二申某-養駢「2 · 3 - b 1 -睹盼-4-某）-2 -氩茱氩基1-3-莱丙酴仿例4 9步驟7之方法，由（R ) - 2 -氟-[4 - ( 9 -溴-2，3 - 二甲基-萘駢[2，3 - b卜睹盼-4 -基）-2 -氟苯氯基】-3 -苯丙酸甲酯（〇 · 2 3克，0 · 4 1毫莫耳），K 0 Η溶液（0 · 5 0毫升之1Ν溶液，0·50毫莫耳），四氫呋喃（6毫升），及甲醇（2毫升）可製得標題化合物之白色固體（0 . 1 7克 ,7 4%) : M S ( Ε I ) : [Μ +]，1 溴同位素式樣，5 4 8 / 5 5 0 ;Methyl ester (0.86 g, 1.8 mmol), K0Η solution (3.6 mL of a 1 N solution, 3β6 mmol), tetrahydrofuran (12 mL), and methanol (4 mL) gave the title compound as a white solid ( 0 · 41 1 g, 63%: 0 pt · R 〇t · [a] 2 5 / D = + 0.87 ° (11.473 mg / mL, MeOH); MS (EI): [M +] 470; Anal. Calc , for C29H23F03S: C, 74.02, H, 4.93, N, 0.00. Found: C, 73.95, H, 5.22, N, 0.12. -127- This paper size applies to China National Standard (CNS) A4 (210 X 297) (Please read the precautions on the back before filling out this page)-· I n mmMme n I in I ον ϋ ϋ · 510900 A7 B7_ V. Description of the invention Example 52 (R) -2-ί4- (9 -Bromo-2. 3-Dishenyl-saipan 『2. 3-bl-_ Hope (please read the precautions on the back before filling this page) -4 -a) -2-argon-Ju M P 3 -Propionate Step 1: Z _ 2 -Fluoro-4-(9 -Shun-2, 3 -Nishimura-Sai 酣 "2 > 3-b 1-嗦 Hope" 4 -yl) __- phenylacetic acid Example 4 The method of step 3 of 9 consists of 2-fluoro-4-(2,3 -dimethyl-naphthalene) 2,3 -b] -panpan-4 -yl) -phenol (1 g, 3.1 Millimoles), acetic anhydride ( 0.36 ml, 3.8 mmol), and pyridine (7.5 ml) to prepare a yellow solid (1 g), which can be used without purification. Example 4 9 The method of step 4 was performed from 2-fluoro-4- (2,3-dimethyl-naphthalenepyrene [2, 3-b] -blaze-4-yl) -phenyl ester (1 · 1 G, 2.9 millimoles), ferric chloride (24. 8 milligrams, G. 15 millimoles), bromine ((3.16 milliliters, 3.2 millimoles) and dichloromethane ( (12 ml) to give the title compound butter (0.86 g, 67%): MS (EI): [Μ +], bromine isotope pattern 4 4 2/4 4 4 0 Step 2: 2-Ar -4-(9 -Ocean-2 < 3 -Dijia Mou-sai gyou "2. 3-b 1 -Seepan-4 -Base) _____- 酣 Example 4 9 Step 5 method, from acetic acid 2 -Fluoro-4-(9 -bromo-2, 3 -di-methyl-naphthalene [2, cold phen-4-yl) -phenyl ester (0.29 g, 0.65 Mmol), K0Η solution ((K79 ml of 1N solution, G.79 mmol), tetrahydrofuran (12 ml), and methanol (7.5 ml) to prepare the title compound as a white solid (0.3 G, 1 0 0 Γ): MS (E I): [M +], 1 bromine isotope pattern, 4 0/4 fl 2. Step 3: (R)-2-argon-"4-(9 -Zhang -2 > 3-two Shenmou-support骈 f 2. 3-b 1--12 8- This paper size is applicable to China National Standard (CNS) A4 (210 χ 297 mm) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7_ V. Description of the invention ( 、 Β) 见望 -4 -a) -2-A rude arga 1-3-Ju bu bian shen _ Example 4 9 step fi method, from 2-fluoro-4-(9 -bromo-2,3 -Dimethyl-naphthalene [2,3 -b-B Hanpan-4 -yl) -phenol (0.29 g, 0.72 mmol), (S)-2 -hydroxy-3- Methyl phenylpropionate (0.19 g, 1.1 mmol), triphenylhydrazone (0.28 g, 1.1 mmol), diethyl azodicarboxylate (0.17 ml, 1 ”millimolar) and anhydrous benzene (5.0 ml) to obtain the title compound as a white solid (0.23 g, 58%). MS (EI): [Μ +], 1 bromoisotope pattern, 5 6 2/5 6 4. Step 4: (R)-2-argon-"4-(9-sea-2 · 3-Ershenmou-raise 骈" 2 · 3-b 1-盼盼 -4- A) -2-Argonyl 1-3-Leprobenzine Example 4 9 Step 7 method, from (R)-2 -fluoro-[4-(9 -bromo-2,3-dimethyl- Naphthalene hydrazine [2,3 -b thiophene-4 -yl) -2 -fluorophenylchloro] -3 -phenylpropyl Methyl ester (0.23 g, 0.41 mol), K0 hydrazone solution (0.50 ml of 1N solution, 0.50 mol), tetrahydrofuran (6 ml), and methanol (6 ml) 2 ml) to obtain the title compound as a white solid (0.17 g, 74%): MS (E I): [Μ +], 1 bromoisotope pattern, 5 4 8/5 50;

Anal. Calc, for C29H22BrF03S : C , 6 3 . 3 9 , H , 4 . 0 4 , N , 0 . 0 0 . Found : C,6 2 . 14, H , 4 . 2 9 , N , 0 . 1 6 ; A n a 1 y t i c a 1 Η P L C 顯示主成分（8 2 · 5 % )。例53 3 -二甲某-養駢「2· 3- b卜睐盼-4-某）-2 ，6 -二異丙基-苯氧基卜乙酸步驟1 乙酴4 - ( 2 , 3 -二甲某-着_「2 . 3 - b 1 -時盼- 4 -某）Anal. Calc, for C29H22BrF03S: C, 6 3. 3 9, H, 4. 0 4, N, 0. 0 0. Found: C, 6 2. 14, H, 4. 2 9, N, 0.1 6; Ana 1 ytica 1 Η PLC displays the main component (8 2 · 5%). Example 53 3-Dimethyl-Nanyang-"2.3-b Bulanpan-4-")-2,6-diisopropyl-phenoxyb-acetic acid Step 1 Ethyl 4-(2, 3- Erjia Mou-zhu _ 「2. 3-b 1-时盼-4 -some）

-2 >___6 -二異两某-笨SB -1 2 9 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------^---------_ (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7 五、發明說明（、4) 彷例4 9步驟3之方法，由4 - ( 2，3 -二甲基-綦駢[2，3 - b ] -睹吩-4 -基）2，6 -二異丙酚（5 · D克，1 3 · 7毫奠耳），乙酐U ·68毫升，17· 8毫莫耳）及毗啶（85毫升）可製得標題化合物之白色固體（5.37克 9 91%):NMR(DMS0-d6):d 8·49 (s，1Η)，7.98 (d, 1Η)，7·49-7·39 (m，3Η)，7.16 (s，2Η)，3.01 (septet，2Η), 2·43 (s， 3H), 2.41 (s, 3H), 1.56 (s, 3H), 1.16 (d, 12H); MS(EI): [M+] 430; Anal. Calc, for C28H30O2S: C, 78.10, H, 7.02, N, 0.00. Found: C, 77.95, H, 7.04, N, 0.07;-2 > ___ 6-Two different two-Stupid SB -1 2 9-This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) ------------- ------- ^ ---------_ (Please read the notes on the back before filling out this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7 4) The method of step 3 of Example 4 9 was carried out from 4-(2,3 -dimethyl-fluorene [2,3-b] -phen-4 -yl) 2,6-diisopropylphenol (5 · D g, 1 3 7 mol), acetic anhydride U · 68 ml, 17.8 mol) and pyridine (85 ml) to obtain the title compound as a white solid (5.37 g 9 91%): NMR (DMS0-d6): d 8.49 (s, 1Η), 7.98 (d, 1Η), 7.49-7 · 39 (m, 3Η), 7.16 (s, 2Η), 3.01 (septet, 2Η) , 2.43 (s, 3H), 2.41 (s, 3H), 1.56 (s, 3H), 1.16 (d, 12H); MS (EI): [M +] 430; Anal. Calc, for C28H30O2S: C, 78.10, H, 7.02, N, 0.00. Found: C, 77.95, H, 7.04, N, 0.07;

Analytical HPLC 顯示主成分（99·3%)。步驟2 Λ酴4-(9-漳-2· 二申某-養駢「2· 3- hi - I»盼 - 4 -某）-2 , β -二黑丙某-荣酯仿例4 9步驟4之方法，由乙酸4 - ( 2，3 -二甲基-莆駢[2，3 _ b ] -時盼-4-基卜2，卜二異丙基-苯酯（〇 · 80克，18 · 5毫莫耳），氯化鐵（16毫克，G · 1毫奠耳），溴（〇 · 13毫升，2 · 6毫莫耳）及二氯甲烷（19毫升）可製得標題化合物之白色固體（〇_ 53克， 56%): NMR(DMSO-d6): δ 8.21 (d, 1H)，7.68-7.62 (m，1H)，7.60-7.42 (m，2H)， 7.18 (s, 2H), 3.00 (septet, 2H), 2.42 (s, 6H), 1.53 (s, 3H), 1.14 (d, 12H). 步驟 3 : 4 - ( 9 -淳-2. 3 -二甲基-# 駢 ί 2 · 3 - b 1 -瞎盼-i-— 甚> -2 . ft -二里丙酚仿例4 9步驟5之方法，由乙酸4 - ( 9 -溴-2 , 3 -二甲基-Analytical HPLC showed the main component (99.3%). Step 2 Λ 酴 4- (9-Zhang-2 · Ershen Mou-yang 骈 2 · 3- hi-I »Pan- 4-Mou) -2, β-Diheparin-Rong ester Example 4 9 The method of step 4 consists of acetic acid 4- (2,3-dimethyl-fluorene [2,3_b] -Shipan-4-ylb 2, b-diisopropyl-phenyl ester (0.80 g , 18 · 5 mmoles), ferric chloride (16 mg, G · 1 mmoles), bromine (0.13 ml, 2.6 mmoles) and dichloromethane (19 ml) to make the title Compound as a white solid (0-53 g, 56%): NMR (DMSO-d6): δ 8.21 (d, 1H), 7.68-7.62 (m, 1H), 7.60-7.42 (m, 2H), 7.18 (s , 2H), 3.00 (septet, 2H), 2.42 (s, 6H), 1.53 (s, 3H), 1.14 (d, 12H). Step 3: 4-(9 -Chun-2. 3 -dimethyl- # 骈 ί 2 · 3-b 1 -Banpan-i-— even > -2. Ft-Dipropylpropionol Example 4 9 Method of step 5 from acetic acid 4-(9 -bromo-2, 3- Dimethyl-

萘駢[2，3-b】-»t吩-4-基）-2，6-二異丙基-苯酯（0·52 克，1.0毫莫耳），Κ0Η溶液（1·64毫升之IN溶液，1.6毫莫耳），四氫呋喃（1 8 · 5毫升），及甲醇（1 1 · 5毫升）可製得標題化合物之乳白色固體（0 · 4 5克，9 5 % ) : ro p 2 1 2 - 2 1 6 °C ; Ν Μ E (DMS0-d6): δ 8.3〇ts, 1H), 8.17 (d, 1H), 7.61 (ddd, 1H), 7.53 (d, 1H), 7.44 (ddd, 1H), 6.92 (s, 2H ), 3.41 (septet, 2H), 2.41 (s, 3H), 1.55 (s, 3H), 1.15 (d, 12H); MS(EI): [M+】，l 溴同位素式樣，466/468; Anal· Calc· for C26H27BrOS: C, 66.80, H, 5.82, N, 0.00. Found: C, 66.17, H, 5.63, N, 0.06 -X30- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） -------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 510900 A7 B7 五、發明說明（Μ) 步驟 4 : 4- ，—1 二基一赛駢「h 3-hi - m m - a- 芒」_二2 . 6 -二異丙基-茱氳甚1- 7.酪田酯 (請先閱讀背面之注意事項再填寫本頁) 將4 - ( 9 -溴-2，3 -二甲基-萘駢[2，3 - b ]-瞎吩-4 -基）一2，6_二異丙酣（0.42克，0·89毫莫耳），溴乙酸甲酯 (〇。36毫升，3·8毫莫耳）及碳酸鉀（〇·42克，3.0毫莫耳）之無水Ν，Ν -二甲基甲ϋ胺（3 5毫升），於室溫及氮氣下攪拌2夭。以水稀釋並以***萃取。減鼷濃縮分餍並層析以石油謎：乙酸乙酯（9 5 : 5)可得標題化合物之白色固體（〇·42 克，87%):NMR(DMS0-d6):<J 8.20(d，lH)， 7.66-7.61 (m，1H)，7·48 (d, 2H)，7·11 (s，2H)，4.56 (s，2H)，3·77 (s，3H)，3.42-3.27 (m, 2H), 2.42 (s, 3H), 1-51 (s, 3H), 1.18 and 1.16 (two doublets, 12H). 步驟δ f 4 一丄J -溴-2 l 3 -二甲基-赛駢「2 · 3 - h卜P塞盼-4，_ 某）二2」β —二異丙某—I氩某1 — 7.酴仿例4 9步驟7之方法，由[4 - ( 9 -溴-2，3 -二甲基-萘駢[2，3-b卜_吩_4-基）-2，6-二異丙基-苯氧基卜乙酸甲酯（（K4克，fl·74毫莫耳），ΚΟίί溶液（〇*89毫升之 1N溶液，（K89毫莫耳），四氫呋喃（6毫升），及甲醇 (2毫升）可製得檫題化合物之白色固體（〇· 37克，95%) :熔點 2 2 8 〜2 3 1 °C，N M R (1) M S 0 - (1 f) ) : <5 1 2 . 9 8 (寬 s，1 Η )，經濟部智慧財產局員工消費合作社印製 8 . 1 9 ( d，1 Η )，7 · 6 5 - 7 · 6 1 (in , 1 Η )，7 · 4 7 ( d，2 Η )，7 · 1 〇 ( s，2 Η ) ,4.44(s,2H),3.40(septet,2H)?2.41(s,3H),1.51(s,3H) 1 · 1 8 和 1 . 1 6 (二雙線，1 2 Η ) ; Μ S ( Ε I ) : [ Μ + ]，1 溴同位素式樣，524,526; Anal· Calc· for C28H29Br03S: C，64,00，H , 5 . 56 , N，0.00, Found: C, 6 3.3 2 , H，5.39 -1 3 1 ~ 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 B7 五、發明說明（w) ，N，(K 01 : A n a 1 y t i c a 1 Η P L C 顯示主成分（9 6 % )。例54 (請先閱讀背面之注意事項再填寫本頁) 」2 R )麵 2 _ 「二一一3—~ 二 M M^^U.2^A^±± -眹 _ _ 卜某）—二^ 氯 ΐτ—ϋ—基―gj— 步驟〗一—5二:^随二3二基」一_二 jLAzJSL 氳—1Naphthalene 骈 [2,3-b]-»tphen-4-yl) -2,6-diisopropyl-phenyl ester (0.52 g, 1.0 mmol), K0Κ solution (1.64 ml of IN solution, 1.6 mmol), tetrahydrofuran (18. 5 ml), and methanol (11. 5 ml) to prepare the title compound as a milky white solid (0.45 g, 95%): ro p 2 1 2-2 16 ° C; NM E (DMS0-d6): δ 8.30ts, 1H), 8.17 (d, 1H), 7.61 (ddd, 1H), 7.53 (d, 1H), 7.44 (ddd , 1H), 6.92 (s, 2H), 3.41 (septet, 2H), 2.41 (s, 3H), 1.55 (s, 3H), 1.15 (d, 12H); MS (EI): [M +], l bromine Isotope style, 466/468; Anal · Calc · for C26H27BrOS: C, 66.80, H, 5.82, N, 0.00. Found: C, 66.17, H, 5.63, N, 0.06 -X30- The paper dimensions apply to Chinese national standards ( CNS) A4 specification (210 X 297 mm) ------------------- Order --------- line (please read the precautions on the back first) (Fill in this page) 510900 A7 B7 V. Description of the invention (M) Step 4: 4-, —1 Diyl-Isai 骈 "h 3-hi-mm-a-mang" _2.6-Diisopropyl- Fructus Corni 1- 7. Butyester (Please read the precautions on the back before filling out this page) will be 4- (9 -bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] -benzophen-4 -yl) 2,6-diisopropylhydrazone (0.42 g, 0.89 mmol) , Methyl bromoacetate (0.36 ml, 3.8 mmol) and potassium carbonate (0.42 g, 3.0 mmol) in anhydrous N, N-dimethylformamide (35 ml), Stir at room temperature under nitrogen for 2 Torr. Dilute with water and extract with ether. Decrease the concentration of the fractions and chromatograph with petroleum mystery: ethyl acetate (95: 5) to obtain the title compound as a white solid (0.42 g, 87%): NMR (DMS0-d6): < J 8.20 ( d, lH), 7.66-7.61 (m, 1H), 7.48 (d, 2H), 7.11 (s, 2H), 4.56 (s, 2H), 3.77 (s, 3H), 3.42- 3.27 (m, 2H), 2.42 (s, 3H), 1-51 (s, 3H), 1.18 and 1.16 (two doublets, 12H). Step δ f 4 1 丄 J -bromo-2 l 3 -dimethyl -Sai 骈 "2 · 3-h P 塞 Saipan-4, _ a) two 2" β-diisopropyl a-I arg a 1-7. 酴 Example 4 9 Step 7 method, from [4- (9-Bromo-2,3-dimethyl-naphthalenepyrene [2,3-b-b-phen_4-yl) -2,6-diisopropyl-phenoxyb-acetate (K4 g , Fl · 74 mmol), ΟΟίί solution (〇 * 89 ml of 1N solution, (K89 mmol), tetrahydrofuran (6 ml), and methanol (2 ml) can be used to prepare the title compound as a white solid (〇 · 37 g, 95%): melting point 2 2 8 ～ 2 3 1 ° C, NMR (1) MS 0-(1 f)): < 5 1 2. 9 8 (width s, 1 Η), Ministry of Economic Affairs Printed by the Intellectual Property Bureau's Consumer Cooperatives 8. 1 9 (d, 1 Η), 7 · 6 5-7 · 6 1 (in , 1 Η), 7 · 4 7 (d, 2 Η), 7 · 1 〇 (s, 2 Η), 4.44 (s, 2H), 3.40 (septet, 2H)? 2.41 (s, 3H), 1.51 ( s, 3H) 1 · 1 8 and 1. 16 (two double lines, 1 2 Η); MS (E I): [Μ +], 1 bromine isotope pattern, 524,526; Anal · Calc · for C28H29Br03S: C , 64,00, H, 5. 56, N, 0.00, Found: C, 6 3.3 2, H, 5.39 -1 3 1 ~ This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 510900 A7 B7 V. Description of the invention (w), N, (K 01: Ana 1 ytica 1 Η PLC shows the main component (96%). Example 54 (Please read the precautions on the back before filling this page) '' 2 R) Surface 2 _ "Two one one three — two MM ^^ U.2 ^ A ^ ±±-眹 _ _ Bum)-two ^ chloro ΐτ-ϋ-base-gj-steps〗 1-2: ^ With two three two bases "one_ 二 jLAzJSL 氲 -1

蓋 ~~~®~isL 仿例4 9步驟1之方法，由3，5 -二溴-對-大菌番醇酸 (8.0克，25·8毫莫耳），草醯氯（2_48毫升，28·4毫莫耳），Ν，Ν-二甲基甲醯胺（2滴），2，3-二甲基-5 -苄呋喃（5*77克，3ΐ·〇毫莫耳），氯化錫（ΐν)(3·30毫升， 2 8 * 4毫莫耳），及無水二氯甲烷U 6 5毫升），可製得標題化合物之固體（2.92 克，2U)，（DMSO-d6):<J 7.8 1(s，2H) 7.28-7.14 (m, 3H), 7.04 (d, 2H), 3.86 (s, 3H), 3.84 (s, 2H), 2.19 (s, 3H), 1.81 (s, 3H); MS(EI)·· [M+]，2 溴同位素式樣，476(25%)，478(50%)，480(25%)· 步驟 2 4 - ( 2 . ?-二甲基-養駢「2· 3 - bl- 蚨喃-4-v基)_____ -?. fi -二溴酚一仿例4 9步驟2之方法，由（2 -苄基-4 , 5 -二甲基-呋喃 -3 -基）-(4 -甲氧基-3， 5 -二溴苯基）-甲酮（2 · 5 2克經濟部智慧財產局員工消費合作社印製，5.30毫莫耳），三溴化硼（3.79毫升，40.0毫莫耳），及二氯甲烷（1 8毫升），可製得標題化合物（〇 · 9 3 克），其可不經純化而使用： (DMSO-d6): δ 10.19 (br s, 1H), 8.01 (d, 1H), 7.98 (s, 1H), 7.56 (s, 2H), 7.51 (d, 1H), 7.44 (ddd, 1H), 7.36 (ddd, 1H), 2.39 (s, 3H), 1.62 (s, 3H); MS(-ESI): [M-H], 2 溴同位素式樣，4 4 3 ( 6 3 )，4 4 5 ( 1 fl 0 % ) , 4 4 7 ( 6 3 % )。 -1 3 2 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 Α7 Β7 五、發明說明（…）步驟 3 ( 2 R ) - 2 -「2 · 6 -二漳-4 - ( 2 . 3 -二审甚-繁_^_ 「2 . 3 - h 1 -眹蹢-4 -某）-茱氬某Ί Ί菜某丙酸-Β-ϋ- (請先閱讀背面之注意事項再填寫本頁) 仿例49步驟6之方法，由4- (9-溴-2, 3-二甲基-蔡駢 [25 3-b】-呋喃-4-基）-2，6-二溴齦（0.88 克，1.97 毫莫耳），（S) -2-羥基-3-苯丙酸甲酯（0·71克，3·94 毫莫耳），三苯膦（1.03克，3·94毫莫耳），偶氮二羧酸二乙酯（〇·62毫升，3.94毫莫耳）及無水苯（3·9毫升），於於室溫下反應可製得標題化合物之固體（1 · 1 5 克，9 6 % ) : NMR (DMSO-d6): δ 8.04 (d，1Η)，8·03 (s，1Η)，7.71 (s，2Η), 7·51-7·24(ιη，8Η), 5.11(dd，lH)，3.63(s，3H)，3.53-3.35 (四線之二重 «雙線 ABXpattem，2H),2.41(s，3H)，1.60(s，3H); MS(EI): [M+]，2 溴同位素式樣，606(52%)，608(100%)，610(52%)· 步驟 4 ( 2R) -2 -「2. 6 -二溴-4- (2, 3-二田甚-案 1 「2 > 3 _ b Ί -映瞒-4 _某）-荣氫某1 - 3 -荣某丙酸仿例4 9步驟7之方法，由（2 R ) - 2 - [ 2，6 -二溴-4 - ( 2 ，3-二甲基-萘駢[2，3-b]-呋喃-4-基）-苯氣基】-3-苯基丙酸甲酯（〇·25克，0.41毫莫耳），Κ0Η溶液（0.82 毫升之1 Ν溶液，0 · 8 2毫莫耳），四氫呋喃（3 · 0毫升） ,及甲醇（1毫升）可製得標題化合物之白色固體 (0·24 克，10 0%) : NMR ( D M S 0 - d 6 ) : 13.11 經濟部智慧財產局員工消費合作社印製 (br s，1H)，8.02 (d，1H), 8.01 (s，1H), 7·66 (s，2H), 7.49-7.21 (m, 8H), 5·19 (t, lH)，3.36(d，2H),2.39(s，3H)，1.58(s,3H); MS(EI):[M+],2 溴同位素式樣，592(50%),594(100%)，596(50%);八11吐€31(：.比1^2911228犷204:(：， 58.61, Η, 3.73, N, 0.00. Found: C, 58.52, H, 4.01, N, 0.05. 例55 (2R)—„- 2 -「4 - ( 9 _ 溴-2 · 3 -二甲某-着駢 f 2 . 3 - h Ί -膾盼 -133- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 ___B7___ 五、發明說明（（^) -4 -某）-2 . 6 -二馬丙某-茱氳某1- 3 -茱甚丙酴步驟 1 ( 2 R ) -2 -「4-（9-淳-2* 3-二申某-養駢「2· 3 - b 1 (請先閱讀背面之注意事項再填寫本頁) -瞎盼~ 4 -某}___- 2 * 6 -二異丙某"·苯氯基1-3 -荣某丙Cover ~~~ ® ~ isL Example 4 9 The method of step 1 consists of 3,5 -dibromo-p-galactanoic acid (8.0 g, 25.8 millimoles), chloramphenicol (2_48 ml, 28.4 mmol), N, N-dimethylformamide (2 drops), 2,3-dimethyl-5 -benzylfuran (5 * 77 g, 3 mmol · mol), chlorine Tin (ΐν) (3.30 ml, 2 8 * 4 mmol) and anhydrous dichloromethane U 6 5 ml) to obtain the title compound as a solid (2.92 g, 2U), (DMSO-d6) : < J 7.8 1 (s, 2H) 7.28-7.14 (m, 3H), 7.04 (d, 2H), 3.86 (s, 3H), 3.84 (s, 2H), 2.19 (s, 3H), 1.81 ( s, 3H); MS (EI) ·· [M +], 2 bromine isotope pattern, 476 (25%), 478 (50%), 480 (25%) · Step 2 4-(2.? -dimethyl -Raises "2 · 3-bl- thio-4--4- group) _____-?. fi-dibromophenol a model 4 9 Step 2 method, from (2-benzyl-4, 5 -dimethyl -Furan-3 -yl)-(4-methoxy-3,5-dibromophenyl) -methanone (2.52 g Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, 5.30 mmol) , Boron tribromide (3.79 ml, 40.0 mmol), and dichloromethane (18 ml), can be prepared Compound (0.93 g), which can be used without purification: (DMSO-d6): δ 10.19 (br s, 1H), 8.01 (d, 1H), 7.98 (s, 1H), 7.56 (s, 2H ), 7.51 (d, 1H), 7.44 (ddd, 1H), 7.36 (ddd, 1H), 2.39 (s, 3H), 1.62 (s, 3H); MS (-ESI): [MH], 2 bromine isotope Specifications, 4 4 3 (6 3), 4 4 5 (1 fl 0%), 4 4 7 (63 3%). -1 3 2-This paper size applies to China National Standard (CNS) A4 (210 X 297) (Mm) 510900 Α7 Β7 V. Description of the invention (…) Step 3 (2 R)-2-"2 · 6-Erzhang-4-(2.3-Second trial even-Traditional _ ^ _" 2.3-h 1-眹蹢 -4 -a)-ruthenium a certain amaranth amaranth a certain propionic acid-Β-ϋ- (Please read the precautions on the back before filling this page) The method of step 49 of Example 49, from 4- (9 -Bromo-2,3-dimethyl-Ceamidine [25 3-b] -furan-4-yl) -2,6-dibromogum (0.88 g, 1.97 mmol), (S) -2- Methyl hydroxy-3-phenylpropionate (0.71 g, 3.94 mmol), triphenylphosphine (1.03 g, 3.94 mmol), diethyl azodicarboxylate (0.62 Ml, 3.94 mmoles) and anhydrous benzene (3.9 ml), which can be prepared by reacting at room temperature Compound solid (1.15 g, 96%): NMR (DMSO-d6): δ 8.04 (d, 1Η), 8.03 (s, 1Η), 7.71 (s, 2Η), 7.51- 7 · 24 (ιη, 8Η), 5.11 (dd, lH), 3.63 (s, 3H), 3.53-3.35 (double-line four-line «double-line ABXpattem, 2H), 2.41 (s, 3H), 1.60 (s , 3H); MS (EI): [M +], 2 bromine isotope pattern, 606 (52%), 608 (100%), 610 (52%) · Step 4 (2R) -2-"2. 6-2 Bromo-4- (2, 3-Nita-case-case 1 "2 > 3 _ b Ί-Ying hide-4 _some)-Rong hydrogen some 1-3-Rong certain propionic acid model 4 9 Step 7 of Method by (2 R)-2-[2,6-dibromo-4-(2, 3 -dimethyl-naphthalenepyrene [2,3-b] -furan-4-yl) -benzene gas group] Methyl-3-phenylpropionate (0.25 g, 0.41 mmol), K0Η solution (0.82 ml of a 1 N solution, 0.82 mmol), tetrahydrofuran (3.0 ml), and methanol (1 ml) can be obtained as a white solid (0.24 g, 100%) of the title compound: NMR (DMS 0-d 6): 13.11 printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs (br s, 1H), 8.02 (d, 1H), 8.01 (s, 1H), 7.66 (s, 2H), 7.49-7.21 (m, 8H), 5.19 (t, lH), 3.36 ( d, 2H), 2.39 (s, 3H), 1.58 (s, 3H); MS (EI): [M +], 2 Bromine isotope pattern, 592 (50%), 594 (100%), 596 (50%) ; 11 11 € 31 (:. Than 1 ^ 2911228 犷 204: (:, 58.61, Η, 3.73, N, 0.00. Found: C, 58.52, H, 4.01, N, 0.05. Example 55 (2R)-„ -2-"4-(9 _ bromo-2 · 3-dimethyl a-骈 f 2. 3-h Ί-脍望 -133- This paper size applies to China National Standard (CNS) A4 (210 X 297 (Mm) 510900 A7 ___B7___ 5. Description of the invention ((^) -4 -some)-2-6-two Ma Bing-Zhu Fang 1-3-Fructus Step 1 (2 R)-2-" 4- （9- 淳 -2 * 3- 二申某-养骈「2 · 3-b 1 (Please read the precautions on the back before filling out this page)-Blindly hope ~ 4-Some} ___- 2 * 6 -Diisopropyl " · Benzyl chloride 1-3 -Rong Mou Bing

酸H 仿例4 9步驟6之方法，由4 - ( 9 -溴-2 , 3 -二甲基-萘駢 [2，3-b]-時盼-4-基）-2，6-二異丙基酚（0·46 克，0.98 毫莫耳），ί S) -2-羥基-3-苯丙酸甲酯（0 · 70克，3 · 9 毫莫耳），三苯瞵（1.02克，3.9毫莫耳），偶氮二羧酸二乙酷（（Κ 6 2毫升，3 · 9毫莫耳）及無水苯（1 · 0毫升），於於油浴（9 0 °C )下反應2 4小時可製得標題化合物之白色固體（〇·20 克，32%),—只（龍30-(16):5 8.19((1，11〇,7.65- 7.60 (m, 1H), 7.50-7.40 (m, 2H), 7.38-7.27 (m, 5H), 7.06 (s, 2H), 4.55 (t, 1H), 3.55 (s, 3H), 3.35-3.19 (m, 4H), 2.41 (s, 3H), 1.49 (s, 3H), 1.13 (d, 6H), 1.06 and 1 · 〇 4 (二雙線，6 H，旋轉異構物）。步驟 2 ( 2R) - 2 -「4- (9-湟-2* 3-二 W 某-棻駢「2* 3- hi -睹im - 4 -某）-2 , fi -二罌丙某-茱氯基]-3 -苯基丙酸仿例49步驟7之方法，由（21?)-2-[4-(9_溴_2,3_二甲基 -綦駢[2, 3-b]-瞎盼-4-基）-2，6-二異丙基-苯氧基卜3- 苯基丙酸甲酯（0·20克，（K31毫莫耳），Κ0Η溶液（1·2毫升經濟部智慧財產局員工消費合作社印製之1 Ν溶液，1 . 2毫莫耳），四氫呋喃（3 . 0毫升），及甲醇（1毫升）可製得標題化合物之白色固體（(Κ 1 8克，9 3 % ):熔點2 2 2 226°C; NMR (DMSO-d6): δ 13.0 (broad s, 1H), 8.20 (d, 1H), 7.64 (ddd, 1H), 7.48-7.46 (m, 2H), 7.38-7.27 (m, 5H), 7.06 (s, 2H), 4.48 (t, 1H), 3.40-3.26 (m, 4H), 2.42 (s, 3H), 1.50 (s, 3H), 1.14 (d, 6H), 1.07 (d, 6H); MS(-ESI): [M-H], 1 溴同位素式樣，558/560; Anal. Calc· forC35H35Br03S: C, 68.28, H, 5.73, N, 0.00. Found: C, 68.15, H, 5.83, N, 0.03; Analytical Η P L C 顯 -1 3 4 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 x 297公釐) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7 五、發明說明（…）示主成分（1 0 0 % )。例5(5 『3-溴-5-(9-淳-2, 3-二申某-赛駢F2. 3- hi-睐盼-4 -某） -2-»茏某1-胺甲醵篦三丁酯將2 -胺基-6 -溴-4 - ( 9 -溴-2，3 -二甲基-萘駢[2 , 3 - b ] "瞎盼-4 -基）-酚ί 0 · 3 8 2克，0 · 8 0 1毫莫耳）及重碳酸第二第三丁酯（Ο β 1 9 1克，0 · 8 7 5毫莫耳）之T H F ( 0 · 8 3 毫升）加熱至？ (TC 1 5小時。稀釋以***並加入矽_。移除***並將趿附物驟層析（9 : 1石油醚/乙酸乙酯）可得標題化合物之白色固體（〇 . 4 4 7克，9 U ):熔點 205〜207oC NMR (DMS0-d6) : δ 9,61(s，lH)，8.55 (2, 1H). 8·19 (d，J = 8 Hz，1H)，7.65 (ddd, J = 8, 6, 2 Hz，1H)，7.52-7.46 (m，3 H)， 7.27 (d, J = 2 Hz, 1H), 2.44 (d, J = 1 Hz, 3H), 1.67 (d, J = 1 Hz, 3H), 1.40 (s, 9 H); MS (El): 2 溴同位素式樣 575 (20%，M+)，577 (50%，M+)，579 (20%，M+)， 519 (50%, M-fH-tBu), 521 (100%, M+H-tBu), 523 (55%, M+H-tBu); Anal. Calc, for C25H23Br2N03S: C, 52.01, H, 4.02, N, 2.43. Found: C, 51.09, H, 3.84, N, 2.28. 例57 9 -海-4 -（ 3 -溴-甲氩某_ 5 -硝茱某）- 2 . 3 -二申某-赛_ 「2 , 3 - b 1 -睹盼將碘甲烷（〇 · 22毫升，3 · 55毫莫耳）及碳酸鉀（0 · 4 9 0克， 3 · 55毫莫耳），於室溫下加至含9-溴-4- (3-溴-甲氧基-5-硝苯基）-2，3 -二甲基-萘駢[2，3 - b卜B害吩（0 · 6 0 0克，1 · 1 8 3 毫莫耳）之Π M F( 8毫升）攪拌溶液。7小時後再加入碘甲烷 (0 . 1毫升，1 . (Π毫莫耳），再攪拌1 7小時。加至水並以乙醚萃取。加入矽_。移除***並將趿附物驟層析（9 5 : 5 一 135 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線"^ιρ· (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 A7 B7 五、發明說明（^4) 石油醚/乙酸乙酯）可得標題化合物之黃色固體（0 · 4 1 6 克，67%):熔點 204 〜2()5°CNMR(DMS0-d6);<y 8·23 (d，J = 8 Hz, 1Η)，8.33 (d，J = 2 Ηζ，1Η)，8.04 (d，J = 2 Ηζ，1Η)，7.69 (ddd，J = 8, 6, 1 Hz，1H)，7.53 (ddd，J = 8, 6, 1 Hz，1H)，7.47 (d，J = 8 Hz，1H)，4.05 (s，3H)， 2.45 (d, J = 1 Hz, 3H), 1.62 (d, J = 1 Hz, 3H); MS (FAB+): 2 溴同位素式樣 519, 521, 523; Anal. Calc, for C21H15Br2N03S: C, 48.39, H, 2.90, N, 2.69. Found: C, 48.16, H, 2.69, N, 2.58. 例58 H 二5 二-海 3 -二申某-赛駢「？ . ：¾ - h Ί - B 寒盼二4 二二2 -甲氫茱胺― 將9-溴-4-(3-溴-甲氣基-5-硝苯基）-2,3-二甲基-萘駢[2，3 - b卜晴吩（〇 . 3 7 2毫升，0 · 7 1 4毫莫耳），二氯化錫 (11)(805毫克，3.57毫莫耳）及乙酸乙酯（4毫升）加熱攪拌至7 0 °C以溶解。3 I)分後，冷卻至室溫，稀釋以乙酸乙酯並加入矽膠。移除乙酸乙酯並將趿附物驟層析（4 : 1石油醜/乙酸乙酯）可得標題化合物之白色固體（ 0 . 3 2 4克， 92%):熔點 1.98 〜200 °C NMR(DMS0-d6);i 8e18(d，J = 8Hz， 1H)，7.64 (ddd，J = 8, 6, 1 Hz，1H)，7.58 (d，J = 8 Hz，1H), 7.50 (ddd，J = 8, 6, 1 Hz, 1H), 6.70 (d, J = 2 Hz, 1H), 6.64 (d, J = 2 Hz, 1H), 5.46 (s, 1H), 3.80 (s, 3H), 2.44 (d, J = 1 Hz, 3H), 1.73 (d, J = 1 Hz, 3H); MS (El): 2 溴同位素式樣 489 (50%, M+), 491 (100%, M+), 493 (60%, M+); Anal. Calc, for C21H17Br2NOS: C, 51.34, H, 3.49, N, 2.85. Found: C, 51.00, H, 3.43, N, 2.71. 例59 Γ3 _ 5 ( 9 一鑛 2 · 3 一 z： 3¾ 一 ^ _ Γ 2 · 3 b 1 一 Bt @ 一 4 - - 2 -申氳茱_ Ί - 酴申酯將溴乙酸甲酯（ 0.2 8 5毫升，3.D1毫莫耳），於室溫下 -1 36- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） ------------Aw--------訂---------線"41^· (請先閱讀背面之注意事項再填寫本頁) 510900 A7 B7 五、發明說明（ιπ) 加至含3-溴-5- ( 9-溴-2， 3-二甲基-萘駢[2, 3_b]_tt 盼-4-基）-2 -甲氣苯胺（0.260克，0.529毫奠耳）及磺 (請先閱讀背面之注意事項再填寫本頁) 酸鉀（0 · 4 1 1克，3 · 0毫莫耳）之D M F ( 1 · ?毫升）攪拌溶液。2天後再加入溴乙酸甲酯（0.135毫升，1.5毫莫耳），再攪拌1天。加至水，濾集固體並以水洗。將固體以石油醚碾製，於6 G °C真空乾燥可得標題化合物之白色固體（0.212 克，71%):熔點 194 〜198°C ;NMR(DMS0-d6);<5 8·17 (dd，J = 8, 1 Ηζ，1Η)，7.63 (ddd，J = 8, 6, 1 Ηζ，1Η)，7.53-7.45 (m，2Η)，6.77 (d，J =2 Hz, 1H), 6.54 (d, J = 2 Hz, 1H), 6.10 (t, J = 7 Hz, 1H), 3.97 (dd, J = 7, 4 Hz, 2H)，3.83 (s, 3H)，3.52 (s，3H)，2.43 (s, 3H)，1.69 (s，3H); MS (FAB+): 2 溴同位素式樣 561，563, 565; Anal. Calc, for C24H21Br2N03S: C，51.17, H，3·76, N, 2.49. Found: C, 50.43, H, 3.63, N, 2.53. 例60 「3-溴-5- (9-溴-2· 3-二申某-赛駢「2. -lit 盼-4 -某） -2 氯茱胺某1 -乙· 將故〇11溶液（11«，（）.64毫升，0.64毫莫耳），於室溫下加至含【3 -溴-5 - ( 9 -溴-2，3 -二甲基-萦駢[2，3 - b ] -瞎吩-4-基）-2-甲氯苯胺卜乙酸甲酯（0.18克，0·32 毫莫耳）之THF(2.5毫升）及甲醇（1.5毫升）攪拌溶液。4小時後移除溶劑並加入水。酸化並以***萃取。經濟部智慧財產局員工消費合作社印製加入矽_。移除***並將吸附物驟層析（7 : 3石油醚/乙酸乙酯〜9:1乙酸乙酯/甲醇）可得標題化合物之白色固體（0 · 1 1 2 克，6 4 % ) ··熔點 > 1 9 0 °C (分解）·· Ν Μ E ( D M S 0 - d 6 ); 8.16 (d, J = 8 Hz, 1H), 7.63 (ddd, J = 8, 6, 1 Hz, 1H), 7.56 (d, J = 8 Hz, 1H), 7.48 (ddd, J = 8, 6, 1 Hz, 1H), 6.72 (d, J = 2 Hz, 111), 6.43 (d, J = 2 Ur. IH), 5,74 (broad s, 1H), 3.83 (s, 3H), 3.46 (s, 2H), 2.42 (s, 3H), 1.71 (s, 3H); MS (FAB+): 2 溴同位素式樣 547, 549, 551; Anal. Calc, for C23H19Br2N03S: C，50.29, H，3.49, N，2·55· Found: C，49.54, H，3.73, N，2.26. 本紙張尺度適用中國國家標準（CNS)A4規格（210 x 297公釐） -137 經濟部智慧財產局員工消費合作社印製 510900 Α7 Β7 五、發明說明（4) 例6 1 (R) -2 -「4-（9- 海-2> 3- 二申某-赛駢「2· 3- hi-睐盼- 4- (請先閱讀背面之注意事項再填寫本頁) t 訂---------線_ 510900 經濟部智慧財產局員工消費合作社印製 A7 B7 五、發明說明) (DMS0-d6): 68.41 (s, 1H), 8.31 (s, 1H), 7.93 (d, 1H), 7.47 (d, 1H), 7.42 (ddd, 1H), 7.32 (ddd, 1H), 6.86 (s, 2H), 2 J6-2.56 (complex m, ABX pattern, 4H), 2.39 (s, 3H), 1.60 (s, 3H), 1.14 (t, 6H); MS(+ESI): [M]+ 360. 步驟 3 r, m 4 - ( 2 , 3 -二甲某-赛 _ Γ 2 . 3 - b 1 - _ 盼-4 -某） -L ft -二Z荣酯彷例49步驟3之方法，由4-(2, 3-二甲基-萘駢[2, 3-b]-瞎盼-4 -基卜2，6 -二乙酚（1 6 · 6克，4 6 · 0毫莫耳），乙酐（5 · 6 6 毫升，59·9毫莫耳），毗啶（92毫升）及二氯甲烷（92毫升），將所得物碾製以丙酬：己烷（1 : 1 )可製得標題化合物之固體（6·85克，3 7%):NMR(DMS0-d6):<y 8.47(s，lH)，7.9?(d， 1H)，7·49-7·34 (m，3H), 7·11 (s，2H), 2·60-2.46 (m, 4H)，2·40 (二重疊 s， 6H)，1·59 (s，3H)，1·13 (t，6H); MS(+ESI): [M+H] 403; Anal. Calc, for C26H2602S: C, 77.57, H, 6.51, N, 0.00. Found: C, 76.46, H, 6.60, N, 0.19. 步驟4 Z _ 4 - ( 9 -淳-?… 3 -二申某-赛駢Γ 2 , 3 - b Ί - Pt盼 - 4·- 某）-2 > -二？\ 茱酷仿例4 9步驟4之方法，由乙酸4-(2,3-二甲基-葉駢[2,3·^] -瞎吩-4 -基）-2，6 -二乙基-苯酯（1 · 〇克，2 · 5毫莫耳），氯化鐵（2 0毫克，0 · 12毫莫耳），溴（2 · 7毫升，2 · 7毫莫耳）及二氯甲烷（25毫升）可製得標題化合物之固體（1 · 2克，100%) :N MR (DMSO-d6): δ 8.20 (d, 1Η), 7.68-7.61 (m, 1H), 7.49 (d, 2H), 7.13 (s, 2H), 2.60- 2.47 (m, 4H), 2.42 (s, 3H), 2.40 (s, 3H), 1.56 (s, 3H), 1.13 (t, 6H); MS(+APCI): [M+H】，1 溴同位素式樣 481/483; Anal. Calc, for C26H25Br02S: C, 64.86, H, 5.23, N, 0.00. Found: C, 63.06, H, 5.13, N, 0.03. 步驟 5 4 · ( 9 -海-2 , 3 -二申某-苯駢 Γ 3 - b 1 - _ 盼-4二基）—-2 > 6 -二乙酿仿例4 9步驟5之方法，由乙酸4 - ( 9 _溴-2，3 -二甲基-萘駢[2，3 - b卜I!富吩-4 -基）-2 , 6 -二乙基-苯酯（1 · 〇克 -1 3 9 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) 訂---------線. 經濟部智慧財產局員工消費合作社印製 510900 Α7 Β7 五、發明說明，2」毫莫耳），KOH溶液（2.5毫升之IN溶液，2· 5毫莫耳），四氫呋喃（2 9 · 7毫升），及足量甲醇可製得含標題化合物固體（(K83克，91%)之均質溶液：NMR(DMS0-d6): δ 8.36 (s, 1H), 8.16 (d, 1H), 7.61 (ddd, 1H), 7.55 (d, 1H), 7.44 (ddd, 1H), 6.88 (s, 2H), 2.76-2.56 (complex m, ABX pattern, 4H), 2.41 (s, 3H), 1.58 (s, 3H), 1.14 (t, 6H); MS(+APCI): [M+H]，1 溴同位素式樣，439/441· 6 Η ) ; M S ( + A P C U : [ Μ + Η ]，〗溴同位素式樣，4 3 9 / 4 4 1。步驟 0 (2R) -2-U-(9-漳-2· 3 - 二甲某-棻駢 Γ2· 3二JlIz- B索盼-4 -某）- 2 . fi -二7：荣氱某1 - 3 -荣丙酸甲1 仿例49步驟6之方法，由4- (9-溴-2，3-二甲基駢 [2，3-1)】-_盼-4 -基）-2, 6-二乙酚（0·83 克，1·89 毫莫耳），（S) -2 -羥基-3-苯丙酸甲_ (2·72克，15·0 毫莫耳），三苯瞵（3·96克，15.0毫莫耳），偶氮二羧酸二乙酯（2.36毫升，15.0毫莫耳）及無水苯（40毫升），於室溫下反應可製得標題化合物之固體（G · 7 4克， 6 5%) : NMR (DMSO-d6): δ 8.18 (d, 1H), 7.66-7.60 (m, 1H), 7.48-7.44 (m，2H)，7.37-7.23 (m，5H)，7.01 (s，2H)，4.69 (t，1H)，3.55 (s，3H)，3.29 (m, 2H), 2.74-2.45 (m, 4H), 2.41 (s, 3H), 1.53 (s, 3H), 1.09 and 1.08 (two t, 6H); MS(+APCI): [M+H]，l 溴同位素式樣，601/603. M S ( + A P C I ) ·· [ Μ + Η ]，1 溴同位素式樣，6 0 1 / 6 0 3 0 步驟 7 (2m -潦-2· :¾-二申某-縈 _Γ2·3 'bl -瞎盼-4 -某）-2 . ft -二Z莶氩某1 Ί茱丙l 仿例4 9步驟7之方法，由（2 R ) - 2 - [ 4 - ( 9 -溴-2 , 3 - 二甲基-萘駢[2，3 - b ]-瞎吩-4 -基）-2，6 -二乙苯氧基] -3-苯丙酸甲醜（0·7克，1.16毫莫耳），Κ0Η溶液（2·3 毫升之1 Ν溶液，2 · 3毫莫耳），四氫呋喃（U · 6毫升） '14 0- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂-----------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印制衣 510900 A7 B7 五、發明說明（吻）Acid H. Example 4 9 The method of step 6 consists of 4-(9 -bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] -timepan-4-yl) -2,6-di Isopropylphenol (0.46 g, 0.98 mmol), ί S) methyl 2-hydroxy-3-phenylpropionate (0.70 g, 3. 9 mmol), triphenylhydrazone (1.02 G, 3.9 mmol), diethyl azodicarboxylate ((K 62 2 ml, 3.9 mmol) and anhydrous benzene (1.0 ml) in an oil bath (90 ° C) The reaction was carried out for 24 hours to obtain the title compound as a white solid (0.20 g, 32%), only (Dragon 30- (16): 5 8.19 ((1, 11〇, 7.65- 7.60 (m, 1H) , 7.50-7.40 (m, 2H), 7.38-7.27 (m, 5H), 7.06 (s, 2H), 4.55 (t, 1H), 3.55 (s, 3H), 3.35-3.19 (m, 4H), 2.41 (s, 3H), 1.49 (s, 3H), 1.13 (d, 6H), 1.06 and 1 · 〇4 (two double lines, 6 H, rotamers). Step 2 (2R)-2-"4 -(9- 湟 -2 * 3- 二 W 某-棻骈「2 * 3- hi-睹 im-4-某） -2, fi -Dipyridyl-Ciucyl] -3 -phenylpropyl The method of step 7 of the acid mimic example 49 consists of (21?)-2- [4- (9_bromo_2,3_dimethyl-fluoren [2, 3-b] -blaze-4-yl) -2,6-diisopropyl-phenoxyb 3-phenylpropane Methyl ester (0.20 g, (K31 mmol), K0Η solution (1.2 ml of 1N solution printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, 1.2 mmol), tetrahydrofuran (3. 0 ml) and methanol (1 ml) to obtain the title compound as a white solid ((K 1 8 g, 93%): melting point 2 2 2 226 ° C; NMR (DMSO-d6): δ 13.0 (broad s , 1H), 8.20 (d, 1H), 7.64 (ddd, 1H), 7.48-7.46 (m, 2H), 7.38-7.27 (m, 5H), 7.06 (s, 2H), 4.48 (t, 1H), 3.40-3.26 (m, 4H), 2.42 (s, 3H), 1.50 (s, 3H), 1.14 (d, 6H), 1.07 (d, 6H); MS (-ESI): [MH], 1 bromine isotope Style, 558/560; Anal. Calc · forC35H35Br03S: C, 68.28, H, 5.73, N, 0.00. Found: C, 68.15, H, 5.83, N, 0.03; Analytical Η PLC -1-3 4-Paper size Applicable to China National Standard (CNS) A4 specification (210 x 297 mm) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7 5. The description of the invention (...) shows the main component (100%). Example 5 (5 "3-bromo-5- (9-chun-2, 3-di-shenmou-sai 骈 F2. 3- hi-lanpan-4 -some) -2-» 茏 some 1-amine formamidine Tris-butyl ester of 2-amino-6-bromo-4-(9 -bromo-2,3-dimethyl-naphthalene [2, 3-b] " 0 · 3 8 2 g, 0 · 8 0 1 mmol) and second and third butyl bicarbonate (0 β 1 9 1 g, 0 · 8 7 5 mmol) in THF (0 · 8 3 ml ) Heated to? (TC 1 5 hours. Dilute with diethyl ether and add silica gel. Remove the diethyl ether and flash chromatography of the condensate (9: 1 petroleum ether / ethyl acetate) to give the title compound as a white solid (0.44 7g ， 9 U): melting point 205 ~ 207oC NMR (DMS0-d6): δ 9,61 (s, lH), 8.55 (2, 1H). 8 · 19 (d, J = 8 Hz, 1H), 7.65 (ddd , J = 8, 6, 2 Hz, 1H), 7.52-7.46 (m, 3 H), 7.27 (d, J = 2 Hz, 1H), 2.44 (d, J = 1 Hz, 3H), 1.67 (d , J = 1 Hz, 3H), 1.40 (s, 9 H); MS (El): 2 bromine isotope pattern 575 (20%, M +), 577 (50%, M +), 579 (20%, M +), 519 (50%, M-fH-tBu), 521 (100%, M + H-tBu), 523 (55%, M + H-tBu); Anal. Calc, for C25H23Br2N03S: C, 52.01, H, 4.02 , N, 2.43. Found: C, 51.09, H, 3.84, N, 2.28. Example 57 9 -Sea-4-(3 -bromo-methylargon _ 5-nitrate)-2. 3-Ershen -Sai_ "2, 3-b 1-see pan iodomethane (0.22 ml, 3.55 mmol) and potassium carbonate (0.490 g, 3.55 mmol) in the chamber Add to the temperature containing 9-bromo-4- (3-bromo-methoxy-5-nitrophenyl) -2,3-dimethyl-naphthalene [2,3 -b b B phenphen (0 · 6 0 0 grams, 1 · 1 8 3 Mol (8 ml) of agitated solution. After 7 hours, add methyl iodide (0.1 ml, 1. (Πmmol) and stir for another 17 hours. Add to water and extract with ether. Add Silicon _. Remove the ether and chromatographically attach the appendages (9 5: 5 to 135-this paper size applies to China National Standard (CNS) A4 (210 X 297 mm) --------- ----------- Order --------- line " ^ ιρ · (Please read the notes on the back before filling out this page) Printed by the Employees' Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (^ 4) Petroleum ether / ethyl acetate) The title compound was obtained as a yellow solid (0 · 4 1 6 g, 67%): melting point 204 ~ 2 (5 ° CNMR (DMS0-d6) ; < y 8 · 23 (d, J = 8 Hz, 1Η), 8.33 (d, J = 2 Ηζ, 1Η), 8.04 (d, J = 2 ， ζ, 1Η), 7.69 (ddd, J = 8, 6, 1 Hz, 1H), 7.53 (ddd, J = 8, 6, 1 Hz, 1H), 7.47 (d, J = 8 Hz, 1H), 4.05 (s, 3H), 2.45 (d, J = 1 Hz, 3H), 1.62 (d, J = 1 Hz, 3H); MS (FAB +): 2 bromine isotope pattern 519, 521, 523; Anal. Calc, for C21H15Br2N03S: C, 48.39, H, 2.90, N, 2.69 . Found: C, 48.16, H, 2.69, N, 2.58. Example 58 H 2 5 2-sea 3-2 Shenmou-Sai 骈 "? .: ¾-h Ί-B Hanpan II 4 222-Methylhydrojugamine ― 9-bromo-4- (3-bromo-methylamino-5-nitrophenyl) -2,3-dimethyl -Naphthyl naphthalene [2,3 -b bufenphen (0.32 ml, 0.714 mmol), tin (11) (805 mg, 3.57 mmol) and ethyl acetate The ester (4 ml) was heated to 70 ° C to dissolve. 3) After cooling to room temperature, dilute with ethyl acetate and add silicone. Removal of ethyl acetate and flash chromatography of the appendages (4: 1 petroleum spirit / ethyl acetate) gave the title compound as a white solid (0.324 g, 92%): melting point 1.98 ~ 200 ° C NMR (DMS0-d6); i 8e18 (d, J = 8Hz, 1H), 7.64 (ddd, J = 8, 6, 1 Hz, 1H), 7.58 (d, J = 8 Hz, 1H), 7.50 (ddd, J = 8, 6, 1 Hz, 1H), 6.70 (d, J = 2 Hz, 1H), 6.64 (d, J = 2 Hz, 1H), 5.46 (s, 1H), 3.80 (s, 3H), 2.44 (d, J = 1 Hz, 3H), 1.73 (d, J = 1 Hz, 3H); MS (El): 2 bromine isotope pattern 489 (50%, M +), 491 (100%, M +), 493 (60%, M +); Anal. Calc, for C21H17Br2NOS: C, 51.34, H, 3.49, N, 2.85. Found: C, 51.00, H, 3.43, N, 2.71. Example 59 Γ3 _ 5 (9 一矿 2 2 · 3 a z: 3¾ a ^ _ Γ 2 · 3 b 1 a Bt @ a 4--2 -Shen Ju Zhu _ Ί-Xanthyl ester will be methyl bromoacetate (0.2 8 5 ml, 3.D1 millimoles ), At room temperature -1 36- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ------------ Aw -------- Order --------- line " 41 ^ · (Please read the precautions on the back before filling in this page) 510900 A7 B7 V. Description of the invention (ιπ) To 3-bromo-5- (9-bromo-2,3-dimethyl-naphthalenepyrene [2, 3_b] _ttpan-4-yl) -2-methylaniline (0.260 g, 0.529 mmol) And sulphur (please read the notes on the back before filling out this page) Stirring solution of potassium acid (0.41 1.1 g, 3.0 mmol) in DMF (1 ·? Ml). Add bromoacetic acid after 2 days Methyl ester (0.135 ml, 1.5 mmol), stirred for an additional day. Add to water, filter the solid and wash with water. Roll the solid with petroleum ether and dry under vacuum at 6 G ° C to obtain the title compound as a white solid. (0.212 g, 71%): melting point 194 to 198 ° C; NMR (DMS0-d6); < 5 8 · 17 (dd, J = 8, 1 Ηζ, 1Η), 7.63 (ddd, J = 8, 6 , 1 Ηζ, 1Η), 7.53-7.45 (m, 2Η), 6.77 (d, J = 2 Hz, 1H), 6.54 (d, J = 2 Hz, 1H), 6.10 (t, J = 7 Hz, 1H ), 3.97 (dd, J = 7, 4 Hz, 2H), 3.83 (s, 3H), 3.52 (s, 3H), 2.43 (s, 3H), 1.69 (s, 3H); MS (FAB +): 2 Bromine isotope pattern 561, 563, 565; Anal. Calc, for C24H21Br2N03S: C, 51.17, H, 3.76, N, 2.49. Found: C, 50.43, H, 3.63, N, 2.53. Example 60 "3-Bromo -5- (9-Bromo-3 -Some) -2 chlorduramine some 1 -B · will be the 〇11 solution (11 «, (). 64 ml, 0.64 millimoles), at room temperature to add [3- -bromo-5-(9 -Bromo-2,3-dimethyl-fluorene [2,3-b] -blphen-4-yl) -2-methylchloroaniline methyl acetate (0.18 g, 0.32 mmol) The solution was stirred with THF (2.5 ml) and methanol (1.5 ml). After 4 hours the solvent was removed and water was added. Acidified and extracted with ether. Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs Join Silicon_. The ether was removed and the adsorbate was subjected to flash chromatography (7: 3 petroleum ether / ethyl acetate to 9: 1 ethyl acetate / methanol) to obtain the title compound as a white solid (0.12 g, 64%). · Melting point> 190 ° C (decomposition) · NM (DMS 0-d 6); 8.16 (d, J = 8 Hz, 1H), 7.63 (ddd, J = 8, 6, 1 Hz, 1H), 7.56 (d, J = 8 Hz, 1H), 7.48 (ddd, J = 8, 6, 1 Hz, 1H), 6.72 (d, J = 2 Hz, 111), 6.43 (d, J = 2 Ur. IH), 5,74 (broad s, 1H), 3.83 (s, 3H), 3.46 (s, 2H), 2.42 (s, 3H), 1.71 (s, 3H); MS (FAB +): 2 bromine Isotope styles 547, 549, 551; Anal. Calc, for C23H19Br2N03S: C, 50.29, H, 3.49, N, 2.55 · Found: C, 49.54, H, 3.73, N, 2.26. This paper scale applies Chinese national standards (CNS) A4 specifications (210 x 297 mm) -137 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 Α7 Β7 V. Description of the invention (4) Example 6 1 (R) -2-"4- (9- Hai -2 > 3- Ershenmou-sai 骈「2 · 3- hi- 睐望-4- (Please read the notes on the back before filling out this page) t Order --------- line_ 510900 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention) (DMS0-d6): 68.41 (s, 1H), 8.31 (s, 1H), 7.93 (d, 1H), 7.47 (d, 1H), 7.42 (ddd, 1H), 7.32 (ddd, 1H), 6.86 (s, 2H), 2 J6-2.56 (complex m, ABX pattern, 4H), 2.39 (s, 3H), 1.60 (s, 3H), 1.14 (t, 6H); MS (+ ESI) : [M] + 360. Step 3 r, m 4-(2, 3-Dimethyl Mo-Sai _ Γ 2. 3-b 1-_ Pan-4-Mo) -L ft-Di-Ze 49 The method of step 3, consisting of 4- (2, 3-dimethyl-naphthalenepyrene [2, 3-b] -blind-4-kib 2,6-diethylphenol (16. 6 g, 4 6.0 mmol), acetic anhydride (5.66 ml, 59.9 mmol), pyridine (92 ml) and dichloromethane (92 ml). (1: 1) to obtain the title compound as a solid (6.85 g, 3 7%): NMR (DMS0-d6): < y 8.47 (s, 1H), 7.9? (D, 1H), 7 · 49-7 · 34 (m, 3H), 7.11 (s, 2H), 2.60-2.46 (m, 4H), 2.40 (two overlapping s, 6H), 1.59 (s, 3H ), 1.13 (t, 6H); MS (+ ESI): [M + H] 403; Anal. Calc, for C26H2602S: C, 77.57, H, 6.51, N, 0.00. Found: C, 76.46, H , 6.60, N, 0.19. Step 4 Z _ 4-(9 -Chun-?… 3-二申某-赛骈 Γ 2 , 3-b Ί-Ptpan-4 ·-a) -2 > -two? The method of step 4 9 of step 4 is based on 4- (2,3-dimethyl-leafylacetate [2,3 · ^]-benzophen-4-yl) -2,6-diethyl acetate. -Phenyl ester (1.0 g, 2.5 mmol), ferric chloride (20 mg, 0.12 mmol), bromine (2.7 ml, 2. 7 mmol) and dichloride Methane (25 ml) yielded the title compound as a solid (1.2 g, 100%): N MR (DMSO-d6): δ 8.20 (d, 1Η), 7.68-7.61 (m, 1H), 7.49 (d , 2H), 7.13 (s, 2H), 2.60- 2.47 (m, 4H), 2.42 (s, 3H), 2.40 (s, 3H), 1.56 (s, 3H), 1.13 (t, 6H); MS ( + APCI): [M + H], 1 bromine isotope pattern 481/483; Anal. Calc, for C26H25Br02S: C, 64.86, H, 5.23, N, 0.00. Found: C, 63.06, H, 5.13, N, 0.03 Step 5 4 · (9 -Hai-2, 3 -Di Shenmou-Benzene Γ 3-b 1-_ Pan-4 Diyl) — 2 > 6-Diethyl Brewing Example 4 9 Step 5 of Method by acetic acid 4-(9 -bromo-2,3-dimethyl-naphthalenepyrene [2,3 -b I I fulphen-4 -yl) -2, 6 -diethyl-phenyl ester (1 · 〇g-1 3 9-This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) (Please read the precautions on the back before filling (This page) Order --------- Line. Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 Α7 Β7 V. Description of the invention, 2 "millimoles, KOH solution (2.5 ml of IN solution, 2 · 5 mmol), tetrahydrofuran (29 · 7 ml), and sufficient methanol to prepare a homogeneous solution containing the title compound solid ((K83 g, 91%): NMR (DMS0-d6): δ 8.36 (s , 1H), 8.16 (d, 1H), 7.61 (ddd, 1H), 7.55 (d, 1H), 7.44 (ddd, 1H), 6.88 (s, 2H), 2.76-2.56 (complex m, ABX pattern, 4H ), 2.41 (s, 3H), 1.58 (s, 3H), 1.14 (t, 6H); MS (+ APCI): [M + H], 1 bromine isotope pattern, 439/441 · 6 Η); MS ( + APCU: [Μ + Η], the bromine isotope pattern, 4 3 9/4 41. Step 0 (2R) -2-U- (9-Zhang-2 · 3-Dijiamou- 棻骈 Γ2 · 3 di JlIz- B Sopan-4 -some)-2. Fi-2: 7 1-3 -Methyl 1-propionate The method of step 6 of Example 49 is based on 4- (9-bromo-2,3-dimethylphosphonium [2,3-1)] -_ pan-4 -yl)- 2, 6-diethylphenol (0.83 g, 1.89 mmol), (S) -2-hydroxy-3-phenylpropanoic acid methyl formaldehyde (2.72 g, 15.0 mmol), Triphenylhydrazone (3.96 g, 15.0 mmol), diethyl azodicarboxylate (2.36 ml, 15.0 mmol) and anhydrous benzene (40 ml) were reacted at room temperature to obtain the title compound. Solid (G · 74 g, 6 5%): NMR (DMSO-d6): δ 8.18 (d, 1H), 7.66-7.60 (m, 1H), 7.48-7.44 (m, 2H), 7.37-7.23 (m, 5H), 7.01 (s, 2H), 4.69 (t, 1H), 3.55 (s, 3H), 3.29 (m, 2H), 2.74-2.45 (m, 4H), 2.41 (s, 3H), 1.53 (s, 3H), 1.09 and 1.08 (two t, 6H); MS (+ APCI): [M + H], 1 bromine isotope pattern, 601/603. MS (+ APCI) ·· [Μ + Η] , 1 Bromine isotope pattern, 6 0 1/6 0 3 0 Step 7 (2m-潦 -2 ·: ¾-Two-shenmo- 萦 _Γ2 · 3 'bl -blind-4 -some) -2. Ft- Two Z argon 1 Example 4 The method of step 7 from (9), using (2 R)-2-[4-(9 -bromo-2, 3 -dimethyl-naphthalenepyrene [2,3-b] -benzophen-4 -yl) -2,6-diethylphenoxy] -3-phenylpropionate (0.7 g, 1.16 mmol), K0Η solution (2.3 ml of 1 N solution, 2.3 mmol) , Tetrahydrofuran (U · 6ml) '14 0- This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) ------------------- -Order ----------- line (please read the notes on the back before filling out this page) Printed clothing 510900 A7 B7 of the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs V. Description of the invention (kiss)

，及足量甲醇可製得均質溶液。由己烷/丙酯再結晶可製得標題化合物之白色固體（〇 · 1 5克，2 2 % ) : N M R (DMS0-d6): δ 12.91 (br s, 1H), 8.18 (d, 1H), 7.63 (ddd, 1H), 7.51-7.42 (m, 2H), 7.36-7.22 (m, 5H), 7.00 (s, 2H), 4.62 (t, 1H), 3.25 (d, 2H), 2.74 (complex m, ABX pattern, 1H), 2.66 (complex m, ABX pattern, 2H), 2.55 (complex m, ABX pattern, 1H)，2.41 (s，3叫 1·53 (s，3H)，1.10 (t，6H); MS(-ESI): [M-H]，1 溴同位素式樣，585/587; Anal. Calc, for C33H31Br03S: C，67.46，H，5.32, N, 0·00· Found: C, 66.84, H, 5.24, N, 0.03. 例62 { f ?.R) - 2 - U - (1 -漳-2 . 3 -二印某-蔡駢 Γ2 , 3 - bl - 禮控/ l甚）—2 · l二g荣氨-甚1 Ί I丙冑胺基L —乙Μ 將（2 R ) - 2 - [ 4 - ( 9 -溴-2 , 3 -二甲基-綦駢[2，3 - b 卜瞎吩-4-基）-2，β-二乙苯氧基]-3 -苯丙酸（〇·5克，（）·89 毫莫耳），1 - ( 3 -二甲胺丙基卜3 -乙基碳化二亞胺鹽酸鹽 (0·34克，1·77毫莫耳），甘胺酸乙酯鹽酸鹽（〇·24克， 1 β 7 2毫莫耳），碳酸鉀（〇 · 5 0克，3 · 6 2毫莫耳）及二氯甲烷 (6毫升）於室溫下攪拌。3天後以二氯甲烷稀釋，以水洗2 次，以食鹽水洗1次，再於硫酸鈉乾燥。吸附至矽膠，層析以己烷：乙酸乙酯（75: 25)可得固體（〇· 4克），處理以ΚΟ Η 溶液U · 1 1毫升之ί Ν溶液，1 · 1 1毫莫耳），四氫呋喃（8 · 9毫升），及足量甲醇可製得均質溶液。於室溫下2 4小時後以 ***稀釋，以1 N H C 1洗1次，以水洗2次，再於硫酸鈉乾燥。減賴濃縮，由己烷/丙酯再結晶可製得白色固體（〇 · 2克 ,3 6 % ) : N M R ( D M S 0 - d 6 ) : ί 1 2 . 5 8 ( b r , s , 1 Η ) , 8 . 5 3 (t , 1 H ), ~ 1 4 1 一本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7 五、發明說明（…） 8.18 (d, 1H), 7.64 (ddd, 1H), 7.52-7.43 (m, 2H), 7.34-7.19 (m, 5H), 6.92 (s, 2H), 4.87 (t, 1H), 3.88-3.70 (二重 β quartets, ABX pattern，2H)，3.31-3.10 (四線之二重叠雙線，ABX pattern，2H)，2·43 (s，3H)，2·23 (s，3H)，2·19 (s，3H)， 1.56 (s,3H); MS(+APCI): [M+H], 1 溴同位素式樣，616/618; Anal· Calc· for C33H30BrNO4S: C，64.29, H，4.90, N，2.27· Found: C，63.97, H，4.48, N， 2.03. 例fi 3 A—( 2 R ) - 2 - U - ( 9 - 漳-2 · 3 -二申某-棻駢「2 , 3 - h Ί - {!索 im -4 -某）-2 , f> -二7,茱氯某1 - 3 -茱丙醯胺某1 乙醱將（2 R ) - 2 - [ 4 - ( 9 -溴-2，3 _二甲基-禁駢[2，3 - b卜B塞盼 - 4 -基）-2‘，6 -二乙苯氧基]-3 -苯丙酸（0 · 4 8克，0 · 8 2毫莫耳），草醯氯（0 · 0 7 1毫升，0。8 1毫莫耳）及苯（1 6 · 3毫升）於室溫下攪拌4Q分。加入甘胺酸乙酯鹽酸鹽（Q . 14克， 1 · 〇毫莫耳）及磺酸鉀（0 · 3 6克，2 · 6毫莫耳），回溫至室溫過夜。趿附至矽_，層析以己烷：乙酸乙酯（9 Ο ·β 1 0 ) 可得固體（Π ·〗7克），處理以Κ0Η溶液（1 · 32毫升之IN溶液，I 3 2毫莫耳），四氫呋喃U (3毫升），及足量甲醇可製得均質溶液。於室®下3G分後以乙謎稀釋，以IN HC1 洗1次，以水洗1次，以食鹽水洗1次，再於硫酸鈉乾燥。減議濃縮，溶於二氯甲烷後於硫酸銷乾燥。減壓濃縮可製得白色固體（(Κ 1 4 克，2 6 % ) : N M R (I) M S 0 - d 6 ) ·· 3 1 2 · 5 1 (br s, 1H), 8.49 (t，1H), 8.17 (d, 1H)，7.62 (ddd，1H)，7.46 (d，2H), 7.32-7.17 (m， 5H)，6.95 (s，1H)，6.94 (s，1H)，4.73 (t，1H)，3.85-3.68 (四線之二重疊雙線 ABXpattem，2H)，3.30-3.10(二重蜃 quartets, ABX pattern, 2H), 2.80-2.50 (complexm, ABX pattern, 4H), 2.41 (s, 3H), 1.54 (s, 3H), 1.06 (t, 6H); MS(-ESI): [M-H], 1 溴同位素式樣，642/644; Anal· Calc· for C35H34BrN04S·· C, 65.21,H, 5.32, N, 2.17. Found: C, 65.03, H, 5.36, N, 2.07. -142- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 ^1^· (請先閱讀背面之注意事項再填寫本頁) 510900 經濟部智慧財產局員工消費合作社印製 A7 B7_ 五、發明說明（⑷）例6 4 I(2 R )_____2 -「4- (9 -漠-2·__3 -二申基-着酣「2 * 3 - b 1 _ 嗦盼 - 4-某）-茱氬某1-3-茱丙酴步驟1 ( 2 R ) - 2 -「4 - ( 9 -湟-?… 3 -二甲某-赛駢「2 · 3 - b卜陳盼-4 -基)____-苯氯某1-3-笨丙酸申酷彷例4 9步驟6之方法，由4 - ( 9 -溴-2 , 3 -二甲基-萘駢 f 2 , 3-b卜時盼-4-基）-酚（5 · 13克，13 · 4毫莫耳），（S) - 2-羥基-3-苯丙酸甲酯（4.8克，26.6毫莫耳），三苯_ (7.0克，26.7 毫莫耳），偶氮二羧酸二乙酯（4.2毫升，26.7毫莫耳）及無水苯（7 4毫升），於室溫下反應可製得標題化合物之固體（4 . 8 克 66%): NMR (DMSO-d6): δ 8.17 (d，J = 8 Hz，1H)，7.62 (ddd，J = 1，6, 8 Hz， 1H)，7.50-7.20 (m 含一單線在 δ 7.22 (J = 8 Hz)，，9H)，7.01 (d，J = 8 Hz， 2H), 5.25 (dd, J = 5, 7 Hz, 1H), 3.67 (s, 3H), 3.25 (complex m, ABX pattern, 2H), 2·41 (s, 3H), 1·51 (s, 3H); MS(+APCI): [M+H]+，1 溴同位素式樣 i， 545/547; Anal. Calc, for C30H25BrO3S: C, 66.06, H, 4.62, N, 0.00. Found: C, 66.15, H, 4.82, N, -0.11. 步驟 2 ( 2 R ) ~ 2 ~· Γ 4 - 一._( 9 -淳 _ 2 ,—„ 3 -二甲基-養酣 Γ 2 > 3 - b 1 - p靠盼-4 -某）-茱氫某]-3 -茱丙鶸仿例4 9步驟7之方法，由（2 R ) - 2 - [ 4 - ( 9 -溴-2，3 - 二甲基-萘駢f 2，3-!)卜瞎盼-4-基）-苯氧基卜3-苯丙酸甲酯（〇·6克，L10毫莫耳），Κ0Η溶液（1·3毫升之1N溶液 ,1.3毫莫耳），四氫呋喃（15.7毫升），及足量甲醇可製得均質溶液其含標題化合物之固體（（Κ 58克，99%): -1 4 3 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------^ i^w— (請先閱讀背面之注意事項再填寫本頁) 510900 A7 _ B7 五、發明說明（+) NMR (DMSO-d6)·· δ 13.14 (br s, 1H)，8.17 (d, J = 8 Hz, 1H), 7.62 (ddd，J = 1, 6, 8, And a sufficient amount of methanol to prepare a homogeneous solution. The title compound was obtained as a white solid by recrystallization from hexane / propyl ester (0.15 g, 22%): NMR (DMS0-d6): δ 12.91 (br s, 1H), 8.18 (d, 1H), 7.63 (ddd, 1H), 7.51-7.42 (m, 2H), 7.36-7.22 (m, 5H), 7.00 (s, 2H), 4.62 (t, 1H), 3.25 (d, 2H), 2.74 (complex m , ABX pattern, 1H), 2.66 (complex m, ABX pattern, 2H), 2.55 (complex m, ABX pattern, 1H), 2.41 (s, 3 is called 1.53 (s, 3H), 1.10 (t, 6H) ; MS (-ESI): [MH], 1 bromine isotope pattern, 585/587; Anal. Calc, for C33H31Br03S: C, 67.46, H, 5.32, N, 0 · 00 · Found: C, 66.84, H, 5.24 , N, 0.03. Example 62 {f? .R)-2-U-(1 -zhang-2. 3 -IIyinmou-Cai 骈 Γ2, 3-bl-courtesy control / l even)-2 · l2 g amine-very 1 1 I propyl amine amino group L-ethane will (2 R)-2-[4-(9 -bromo-2, 3 -dimethyl-fluorene [2,3-b Phen-4-yl) -2, β-diethylphenoxy] -3 -phenylpropanoic acid (0.5 g, () · 89 mmol), 1-(3-dimethylaminepropyl 3 -Ethylcarbodiimide hydrochloride (0.34 g, 1.77 mmol), ethyl glycine hydrochloride (0.24 g, 1 β 7 2 mmol) , Potassium carbonate (0.50 g, 3.62 mmol) and dichloromethane (6 ml) were stirred at room temperature. After 3 days, diluted with dichloromethane, washed twice with water, and washed with brine 1 Then, it was dried over sodium sulfate, adsorbed to silica gel, and chromatographed with hexane: ethyl acetate (75:25) to obtain a solid (0.4 g), which was treated with ΟΟΟ solution U · 1 1 ml of Ν solution , 1.1 mol), tetrahydrofuran (8.9 ml), and a sufficient amount of methanol to prepare a homogeneous solution. After 24 hours at room temperature, it was diluted with ether, washed once with 1 N H C 1, washed twice with water, and then dried over sodium sulfate. Reduce the concentration and recrystallize from hexane / propyl ester to obtain a white solid (0.2 g, 36%): NMR (DMS 0-d 6): ί 1 2. 5 8 (br, s, 1 Η) , 8. 5 3 (t, 1 H), ~ 1 4 1 A paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) -------------- ------ Order --------- line (Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7 V. Description of the invention (…) 8.18 (d, 1H), 7.64 (ddd, 1H), 7.52-7.43 (m, 2H), 7.34-7.19 (m, 5H), 6.92 (s, 2H), 4.87 (t, 1H), 3.88-3.70 ( Double β quartets, ABX pattern, 2H), 3.31-3.10 (two of four lines overlap double lines, ABX pattern, 2H), 2.43 (s, 3H), 2.23 (s, 3H), 2.19 (s, 3H), 1.56 (s, 3H); MS (+ APCI): [M + H], 1 bromine isotope pattern, 616/618; Anal · Calc · for C33H30BrNO4S: C, 64.29, H, 4.90, N , 2.27 · Found: C, 63.97, H, 4.48, N, 2.03. For example, fi 3 A— (2 R)-2-U-(9-Zhang-2 · 3-Ershenmou-棻骈 2, 3 -h Ί-{! 索 im -4 -some) -2, f > Amine 1 acetamidine (2 R)-2-[4-(9 -bromo-2,3 _ dimethyl-contained [2,3 -b B B Cepan-4 -yl) -2 ', 6-Diethylphenoxy] -3 -phenylpropionic acid (0.48 g, 0.82 mol), chloramphenicol (0. 0 7 1 ml, 0.8 1 mol) and Benzene (16. 3 ml) was stirred at room temperature for 4Q minutes. Ethyl glycine hydrochloride (0.14 g, 1.0 mmol) and potassium sulfonate (0.36 g, 2 · 6 mmol), warm to room temperature overnight. Attach to silica gel, chromatograph with hexane: ethyl acetate (9 0 · β 1 0) to obtain a solid (Π · 〖7 g), treat with A homogeneous solution can be prepared by using K0Η solution (1.32 ml of IN solution, I 3 2 mmol), tetrahydrofuran U (3 ml), and sufficient methanol. After 3G points in the chamber®, dilute with acetone, wash once with IN HC1, once with water, once with saline, and then dry over sodium sulfate. Reduce by concentration, dissolve in dichloromethane and dry on sulfuric acid pin. Concentrated under reduced pressure to obtain a white solid ((K 1 4 g, 26%): NMR (I) MS 0-d 6) ·· 3 1 2 · 5 1 (br s, 1H), 8.49 (t, 1H ), 8.17 (d, 1H), 7.62 (ddd, 1H), 7.46 (d, 2H), 7.32-7.17 (m, 5H), 6.95 (s, 1H), 6.94 (s, 1H), 4.73 (t, 1H), 3.85-3.68 (two-overlaid double-line ABXpattem, 2H), 3.30-3.10 (double 蜃 quartets, ABX pattern, 2H), 2.80-2.50 (complexm, ABX pattern, 4H), 2.41 (s, 3H), 1.54 (s, 3H), 1.06 (t, 6H); MS (-ESI): [MH], 1 bromine isotope pattern, 642/644; Anal · Calc · for C35H34BrN04S ·· C, 65.21, H, 5.32, N, 2.17. Found: C, 65.03, H, 5.36, N, 2.07. -142- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) -------- ------------ Order --------- line ^ 1 ^ · (Please read the precautions on the back before filling in this page) 510900 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs System A7 B7_ V. Description of the invention (⑷) Example 6 4 I (2 R) _____ 2-"4- (9-Mo-2 · __3-Ershenji-Zhuan" 2 * 3-b 1 _ hope-4 -A)-Zhua arga 1-3-Zhu Bingxi step 1 (2 R)-2-"4-(9-湟-?… 3-Dimethyl Mou-Saiyan "2 · 3-b Bu Chen Pan-4-) ____-Benzyl chloride 1-3-benzyl propanoic acid Shenku model 4 9 Method of step 6, from 4 -(9 -bromo-2, 3 -dimethyl-naphthalenepyrene f 2, 3-b buspan-4-yl) -phenol (5.13 g, 13.4 mmol), (S)- Methyl 2-hydroxy-3-phenylpropionate (4.8 g, 26.6 mmol), triphenyl_ (7.0 g, 26.7 mmol), diethyl azodicarboxylate (4.2 ml, 26.7 mmol) ) And anhydrous benzene (74 ml) at room temperature to give the title compound as a solid (4.8 g 66%): NMR (DMSO-d6): δ 8.17 (d, J = 8 Hz, 1H) , 7.62 (ddd, J = 1, 6, 8 Hz, 1H), 7.50-7.20 (m with a single line at δ 7.22 (J = 8 Hz), 9H), 7.01 (d, J = 8 Hz, 2H) , 5.25 (dd, J = 5, 7 Hz, 1H), 3.67 (s, 3H), 3.25 (complex m, ABX pattern, 2H), 2.41 (s, 3H), 1.51 (s, 3H) ; MS (+ APCI): [M + H] +, 1 bromine isotope pattern i, 545/547; Anal. Calc, for C30H25BrO3S: C, 66.06, H, 4.62, N, 0.00. Found: C, 66.15, H , 4.82, N, -0.11. Step 2 (2 R) ~ 2 ~ · Γ 4-a. _ (9 -chun_ 2,-„3 -dimethyl-saccharification Γ 2 > 3 -b 1-p rely on -4-a)-Juhydrogen]-3-Zhu Bingxiong Example 4 9 Method of step 7, from (2 R)-2-[4-(9 -Bromo-2, 3-Dimethyl-naphthalene 骈 f 2,3-!) Bublamine-4-yl) -phenoxybub 3-phenylpropanoate (0.6 g, L10 mmol), K0Η solution ( 1.3 ml of a 1N solution, 1.3 mmol), tetrahydrofuran (15.7 ml), and a sufficient amount of methanol to obtain a homogeneous solution containing the title compound as a solid ((K 58 g, 99%): -1 4 3- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) -------------------- Order --------- ^ i ^ w— (Please read the notes on the back before filling this page) 510900 A7 _ B7 V. Description of the invention (+) NMR (DMSO-d6) ·· δ 13.14 (br s, 1H), 8.17 (d, J = 8 Hz, 1H), 7.62 (ddd, J = 1, 6, 8

Hz, 1H), 7.48-7.20 (m 含一單線在 δ 7.22 (J = 8 Hz)，9H), 7.00 (d, J = 8Hz, 1H), 7.48-7.20 (m with a single line at δ 7.22 (J = 8 Hz), 9H), 7.00 (d, J = 8

Hz, 2H), 5.08 (dd，J = 5, 8 Hz，1H), 3.32 - 3.15 (四線之二重疊雙線,ABX Pattern, 2H), 2.41 (s, 3H), 1.53 (s, 3H); MS(+APCI): [Μ+ΗΓ, 1 溴同位素式樣，531/533; Anal. Calc· for C29H23Br03S: C, 65.54, H, 4.36, N, 0.00. Found: C, 65.51, H, 4.61, N, 0.09. 例f)5 J^2 S ) 一馨 3-二_ 某應養酣「2> 3 - b 1 - Bt m 二A二基）. 6 -二甲茱藿，某Ί - 3 -茱丙酸步驟 1 ( 2 S ) - ? -「4 - ( 氧-2 · 3 - 二甲某-寨駢 f 2 · 3-bl -g索盼-4 -甚）-2 . β -二申莱氢基"i Ί茱丙鶸申酯仿例4 9步驟6之方法，由4 - ( 9 -溴-2，3 -二甲基-萘駢f 2，3 - b】-晦吩-4 -基）-2，6 ~二甲酚（1 0 · 4克， 25.4毫莫耳），（S) -2-羥基-3-苯丙酸甲酯（13.7 克，7 6 · 〇毫莫耳）^三苯膦（2 0 · 0克，？ 6 · 3毫莫耳），偶氮二羧酸二乙酷（1 2毫升，7 6 , 2毫莫耳）及無水 T H F ( 1 3 9毫升），於室溫下反應可製得標題化合物之粘泡沫（8 · 6 6 克，5 9 % : 0 P t · R 〇 t · [ a ] 2 5 / D = - 4 4 · 9 ° ( 9 · 1 8 8 mg/mL，MeOH); NMR (DMS0-d6): δ 8.18 (d，J = 8 Hz，1H)，7·62 (ddd，J = 2, 6, 8Hz, 2H), 5.08 (dd, J = 5, 8 Hz, 1H), 3.32-3.15 (two-over-two overlapping double lines, ABX Pattern, 2H), 2.41 (s, 3H), 1.53 (s, 3H) ; MS (+ APCI): [Μ + ΗΓ, 1 bromine isotope pattern, 531/533; Anal. Calc · for C29H23Br03S: C, 65.54, H, 4.36, N, 0.00. Found: C, 65.51, H, 4.61, N, 0.09. Example f) 5 J ^ 2 S) Yixin 3-di _ a certain nutrient 酣 2 > 3-b 1-Bt m diA diyl). 6-Dimethyl rutae, a certain Ί-3 -Juproic acid step 1 (2 S)-?-"4-(Oxygen-2 · 3-Dimethyl-Falcon f 2 · 3-bl -g Sopan-4-even) -2. Β -Two Shenlai Hydroxy " i rutapropanyl ester 4 Example 9 The method of step 6 is based on -4 -yl) -2,6 to xylenol (10.4 g, 25.4 mmol), methyl (S) -2-hydroxy-3-phenylpropanoate (13.7 g, 76 g) Moore) ^ Triphenylphosphine (20.0 grams,? 6.3 millimoles), diethyl azodicarboxylate (12 mL, 76, 2 millimoles) and anhydrous THF (1 3 9 ml), reacted at room temperature to prepare a viscous foam of the title compound (8.66 g, 59%: 0 P t · R 〇t · [ a] 2 5 / D =-4 4 · 9 ° (9 · 1 8 8 mg / mL, MeOH); NMR (DMS0-d6): δ 8.18 (d, J = 8 Hz, 1H), 7.62 ( ddd, J = 2, 6, 8

Hz，1H)，7.51-7.42 (m，2H), 7.36-7.23 (m，5H)，6.98 (s，2H)，4.78 (t，J = 7 Hz, 1H), 3.56 (s, 3H), 3.29 (m, 2H), 2.41 (s, 3H), 2.22 (s, 3H), 2.17 (s, 3H), 1.54 (s, 3H); MS(+APCI): [M+H], 1 溴同位素式樣，573/575; Anal. Calc· for C32H29Br03S: C, 67.01, H, 5.10, N, 0.00. Found: C, 66.72, H, 4.86, N, 0.12. 步驟 2 ( 2S ) - 2 - U - ( -漳-2 · 3 - 二申基-養麗—13-Jb 1 -蹿盼-4 -基）-2 · ft -二甲篆氬某Ί - 3 -荣丙_ 仿例49步驟7之方法，由（2S) -2-[4-(9-溴-2，3-二甲基"·萘駢[2， 3-b】-B寒吩-4-基）-2，6 -二甲苯氧基]-3 -144- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) --------訂---------線. 經濟部智慧財產局員工消費合作社印制取 510900 A7 B7 ------ ----- 五、發明說明（IG ) -苯丙酸甲酯（4·0克，6·97毫莫耳），Κ0Η溶液（8·4毫升之1S溶液，8·4毫莫耳），四氫呋喃（99_6毫升）， (請先閱讀背面之注意事項再填寫本頁) 及足量甲醇可製得均質溶液固體。由2%以乙酸乙酯/己烷再結晶可得標題化合物之固體（1.45克，3?%):熔點 134-139°C； Opt. Rot. [a]25/D = -35.86° (10.040 mg/mL, MeOH); NMR (DMSO- d6): δ 12.92 (br s, 1H), 8.17 (d, J = 8 Hz, 1H), 7.63 (ddd, J = 2,6,8 Hz, 1H), 7.52-Hz, 1H), 7.51-7.42 (m, 2H), 7.36-7.23 (m, 5H), 6.98 (s, 2H), 4.78 (t, J = 7 Hz, 1H), 3.56 (s, 3H), 3.29 (m, 2H), 2.41 (s, 3H), 2.22 (s, 3H), 2.17 (s, 3H), 1.54 (s, 3H); MS (+ APCI): (M + H), 1 bromine isotope pattern , 573/575; Anal. Calc · for C32H29Br03S: C, 67.01, H, 5.10, N, 0.00. Found: C, 66.72, H, 4.86, N, 0.12. Step 2 (2S)-2-U-(- Zhang-2 · 3-Ershenji-Yangli—13-Jb 1 -Yanpan-4 -ji) -2 · ft-Dimethyl argon argon -3-Rong Bing_ The method of step 7 of Example 49, From (2S) -2- [4- (9-bromo-2,3-dimethyl) " · naphthalene [2, 3-b] -Bhanphen-4-yl) -2,6-xylene Oxy] -3 -144- This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) (Please read the precautions on the back before filling this page) -------- Order- -------- line. Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7 ------ ----- V. Invention Description (IG)-Methyl Phenylpropionate (4 0 g, 6.97 mmoles), K0Η solution (8.4 ml of 1S solution, 8.4 mmoles), tetrahydrofuran (99-6 ml), (please read first Note on the back, fill in this page again) and a sufficient amount of methanol can make a homogeneous solution solid. Recrystallization from 2% ethyl acetate / hexane gave the title compound as a solid (1.45 g, 3%): melting point 134-139 ° C; Opt. Rot. [A] 25 / D = -35.86 ° (10.040 mg / mL, MeOH); NMR (DMSO- d6): δ 12.92 (br s, 1H), 8.17 (d, J = 8 Hz, 1H), 7.63 (ddd, J = 2, 6, 8 Hz, 1H) , 7.52-

7.42 (m, 2H), 7.37-7.21 (m, 5H), 6.97 (s, 2H), 4.72 (t, J = 7 Hz, 1H), 3.25 (d, J = 7 Hz, 2H), 2.41 (s, 3H), 2.25 (s, 3H), 2.22 (s, 3H), 1.54 (s, 3H); MS(-ESI): [M-H]*, 1 溴同位素式樣，557/559; Anal. Calc, for C31H27Br03S: C, 66.55, H, 4.86, N, 0.00. Found: C, 66.17, H, 4.87, N, 0.01; Analytical HPLC 顯示主成分（9 8 · 1 % )。例66 (2R) -2- ί 4 - ( 9 - H - 2 3 -二甲基-氯-J Η-棻駢 Γ 2 > 3 - bl -嗾盼-4 -某）-2 . ft -二申茱氬甚1 Ί茱丙醣由（2R) -2-[4-(9-溴-2, 3-二甲基-萘駢[2，3-b] -瞎吩-4 -基）-2 , 6 -二甲苯氧基卜3 -苯丙酸（0 · 5克， 0.89毫莫耳），冰醋酸（6.6毫升）及30%過氣化氫溶液 (1.0毫升，9 ·8毫莫耳）可得混液，立即稀釋以水並以乙_萃取。層析以甲醇/二氯甲烷可製得標題化合物之淡黃色固體（〇·12克，23%) : Opt,Rot.[a】25/D=+29.57° 經濟部智慧財產局員工消費合作社印製 (7.88 mg/mL, MeOH); NMR (DMSO-d6): δ 13.10 (br s, 1H), 8.28 (d, J = 8 Hz, 1H)，7·74 (ddd，J = 1，7, 8 Hz，1H)，7.63 (ddd，J = 1，7, 8 Hz，1H)，7·39 (d，J = 8 Hz, 1H), 7.36-7.18 (m, 5H), 7.01 (s, 1H), 6.89 (s, 1H), 4.69 (t, J = 7 Hz, 1H), 3.23 (m, 2H), 2.24, 2.21, 2.20, 2.18 (4 s, mixture of sulfoxide diastereomers, 6H), 2.17 (s，3H), 1.42 (s，3H); MS(-APCI): [M-Η]·，1 溴同位素式樣，573/575; Anal. Calc, for C31H27Br04S: C, 64.70, H, 4.73, N, 0.00. Found: C, 64.18, H, 4.44, N, -0.03. Analytical HPLC 顯示二主峯（45.16%，47·72%)，a -14 5- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 經濟部智慧財產局員工消費合作社印製 A7 B7 五、發明說明（咐）例67 (R ) -2 -『4- ( 2· 3-二甲基-養財「2* 3~bl_B拿盼-4 -基） _ 2 »________二乙苯氯基_1 _ 3 •苯丙酸— 步驟 1 ( 2 R ) - 2 - U - ( 2 . 3 -二 g 某-赛駢「2 . 3 - h 1 - lit 盼 -4 -某）-2 . fi -二乙茏氮甚1 - 3 -茱丙酴甲酯仿例4 9步驟6之方法，由4 - ( 2，3 -二甲基-萘駢 [2，3-h 卜瞎盼-4-基）-2，6-二乙酚（0.84克，2· 33 毫莫耳），（S) -2-羥基-3-苯丙酸甲酯（3 · 36克， 18.6毫莫耳），三苯_ (4.8克，18.3毫莫耳），偶氮二羧酸二乙酯（2·92毫升，18·5毫莫耳）及無水苯（75 毫升），於室溫下反應可製得標題化合物之固體（〇 . 5 0 克，4 2%) : NMR(DMSO-d6): δ 8.44 (s，1Η)，7.94 (d，J = 8 Hz, 1Η)， 7.48-7.22 (m, 8H), 6.99 (s, 2H), 4.69 (t, J = 7 Hz, 1H), 3.55 (s, 3H), 3.27 and 3.22 (二重叠 dd，J = 6，13 Hz, 2H)，2.70-2.40 (complex m，ABX pattern, 4H)， 2.38 (s, 3H), 1.53 (s, 3H), 1.10 and 1.09 (二重叠 triplets, J = 8 Hz, 6H); MS(+APCI): [M+H]+，523. 步驟 2 (21〇-2-1~4-(2.3-二甲某-着駢「2.3 41-蹿盼 -4 _基）____- 2· 6_二乙笨氯某1~3~篆丙酸仿例4 9步驟7之方法，由（2 R ) - 2 _[ 4 - ( 2，3 -二甲基 -綦駢[2, 3-b】-瞎盼-4-基）-2，6-二乙苯氧基]-3-苯丙酸甲酯（（K46克，0·88毫莫耳），Κ0Η溶液（1·1毫升之1»溶液，1」毫莫耳），四氫呋喃（12.6毫升），及足量甲醇可製得均質溶液含標題化合物白色固體（〇 . 4 3克 -1 4 6 ~ 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) i 訂---------線_ 510900 A7 B7 五、發明說明（ιβ ) 89%): NMR (DMSO-d6): δ 12.91 (brs, 1H), 8.44 (s, 1H), 7.94 (d, J = 8 Hz, 1H), (請先閱讀背面之注意事項再填寫本頁) 7.47-7.22 (m, 8H), 6.98 (s, 2H), 4.61 (t$ J = 7 Hz, 1H), 3.25 (d, J = 7 Hz, 2H), 2.72 (complex m, ABX pattern, 1H), 2.66 (二重 β quartets, J = 8 Hz, 2H), 2.55 (complex m, ABX pattern, 1H), 2.38 (s, 3H), 1.55 (s, 3H), 1.10 and 1.09 ( 二重 llg triplets, J = 8 Hz, 6H); MS(-ESI): [M-H]·, 507; Anal. Calc, for C33H3203S · 0.6H2O: C, 76.30, H, 6.44, N, 0.00. Found: C, 76.44, H, 6.49, N, 0.04. 例68 {(2R)-2-「4-(2· 3 -二申某-赛駢「2, 3:bl j室-盼-4 --里」_ j , fi -二又架氣某Ί Ί茱丙醣胺1 乙酸仿例63之方法，由（2R}-2-[4-(2,3 -二甲基-萘駢 [2, 3-b]-瞎盼-4-基）-2, 6 -二乙苯氯基]-3-苯丙酸（0.27 克，（K53毫莫耳），草醯氯（〇·〇46毫升，0·53毫莫耳）， Ν，Ν-二甲基甲醯胺（2滴），苯（9毫升），甘胺酸乙酯鹽酸鹽（fl · 18克，1 · 0毫莫耳）及磺酸鉀（〇 · 46克，3 · 33毫莫耳），於室溫下可得固體，吸附至矽膠，層析以己烷：乙酸乙 _(9Π:10)。將所得固體（G.18克）處理以K0H溶液（2·34 毫升之1 Ν溶液，2 · 3 4毫莫耳），四氫呋喃（1 0毫升），及足量甲醇可製得均質溶液〇可得標題化合物之淡黃色固體 (0 η 1 0 克，3 3 % ) : NMR (DMSO-d6): δ 12.52 (br s, 1Η)，8·48 (t，J = 6 Ηζ，經濟部智慧財產局員工消費合作社印製 1Η), 8·43 (s, 1Η), 7·94 (d，J = 8 Ηζ，1Η)，7.48-7.16 (m，8Η)，6.93 (s，2Η), 4.73 (t, J = 7 Hz, 1H), 3.79 and 3.73 (二重 || dd，J = 6, 17 Hz, 2H), 3.24 (dd，J = 7, 14 Hz, 1H), 3.15 (dd, J = 7, 14 Hz, 1H), 2.80-2.50 (complex m, ABX pattern, 4H)), 2.39 (s, 3H), 1.56 (s, 3H), 1.07 (t, J = 8 Hz, 6H); MS(+APCI): [M+H]+, 566; Anal. Calc, for C35H35N04S: C, 74.31, H, 6.24, N, 2.48. Found: C, 74.11, H, 6.69, N, 2.24 一 147- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印制衣 510900 A7 B7_ 五、發明說明（ι4) 例69 4 一_( 2 4 —_3 ~ 二申某-養勝 __「2, 喃-4-某）~ 2 « 6 -二乙酚步驟】 (2 -节某-4 , 5 -二甲眹喃-3 -某）-（4 -申氫某- 3 . 5 -二乙茱某）-申酗仿例49步驟1之方法，由3 , 5-二乙基-對-大諸番醇酸 (1 0 · 6 6克，5 1 · 2毫莫耳；依三步驟，由4 -溴-2 , 6 -二乙苯胺及依 J . L i P 〇 w i t z 及 T · C 〇 h e II，J · 0 r g · C h e ro · 1 9 6 5， 30， 3891-3894 ; C.K.Bradsher.W A ； J.Aro.Chem.Soc. 1 9 5 4, 76，2 3 5 7 - 2 3 6 2 ; J.Alexander, 0 r g. Prep.7.42 (m, 2H), 7.37-7.21 (m, 5H), 6.97 (s, 2H), 4.72 (t, J = 7 Hz, 1H), 3.25 (d, J = 7 Hz, 2H), 2.41 (s , 3H), 2.25 (s, 3H), 2.22 (s, 3H), 1.54 (s, 3H); MS (-ESI): [MH] *, 1 bromine isotope pattern, 557/559; Anal. Calc, for C31H27Br03S: C, 66.55, H, 4.86, N, 0.00. Found: C, 66.17, H, 4.87, N, 0.01; Analytical HPLC showed the main component (98 · 1%). Example 66 (2R) -2- 4-(9-H-2 3 -dimethyl-chloro-J Η- 棻骈 Γ 2 > 3-bl-嗾望 -4--)-2. Ft- Distigmine arginine 1 rutacarbotriose consists of (2R) -2- [4- (9-bromo-2, 3-dimethyl-naphthalenepyrene [2,3-b] -benzophen-4-yl) -2, 6-xylyloxyb- 3-phenylpropionic acid (0.5 g, 0.89 mmol), glacial acetic acid (6.6 ml) and 30% hydrogenated solution (1.0 ml, 9.8 mmol) Ear) can be mixed, immediately diluted with water and extracted with ethyl acetate. Chromatography with methanol / dichloromethane can prepare the title compound as a pale yellow solid (0.12 g, 23%): Opt, Rot. [A] 25 / D = + 29.57 ° (7.88 mg / mL, MeOH); NMR (DMSO-d6): δ 13.10 (br s, 1H), 8.28 (d, J = 8 Hz, 1H), 7.74 (ddd, J = 1, 7 ,, 8 Hz, 1H), 7.63 (ddd, J = 1, 7, 8 Hz, 1H), 7.39 (d, J = 8 Hz, 1H), 7.36-7.18 (m, 5H), 7.01 (s, 1H ), 6.89 (s, 1H), 4.69 (t, J = 7 Hz, 1H), 3.23 (m, 2H), 2.24, 2.21, 2.20, 2.18 (4 s, mixture of sulfoxide diastereomers, 6H), 2.17 (s , 3H), 1.42 (s, 3H); MS (-APCI): [M-Η] ·, 1 bromine isotope pattern, 573/575; Anal. Calc, for C31H27Br04S: C, 64.70, H, 4.73, N, 0.00. Found: C, 64.18, H, 4.44, N, -0.03. Analytical HPLC shows two main peaks (45.16%, 47 · 72%), a -14 5- This paper is in accordance with China National Standard (CNS) A4 specifications (210 X 297 mm) 510900 A7 B7 printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 5. Explanation of the invention (command) Example 67 (R) -2-"4- (2 · 3-dimethyl-economy" 2 * 3 ~ bl_B Napan-4-Ji) _ 2 »___ _____Diethylphenylchloro_1 _ 3 • Phenylpropanoic acid — Step 1 (2 R)-2-U-(2.3. Dig -Sai-"2. 3-h 1-lit Pan-4 -A) -2.fi-diethylhydrazine and even 1-3-propionate methyl ester Example 4 9 The method of step 6 consists of 4-(2,3-dimethyl-naphthalenepyrene [2,3- h Bublant-4-yl) -2,6-diethylphenol (0.84 g, 2.33 mmol), (S) methyl 2-hydroxy-3-phenylpropionate (3.36 g, 18.6 mmol), triphenyl benzene (4.8 g, 18.3 mmol), diethyl azodicarboxylate (2.92 ml, 18.5 mmol) and anhydrous benzene (75 ml) in the chamber Reaction at room temperature gave the title compound as a solid (0.50 g, 42%): NMR (DMSO-d6): δ 8.44 (s, 1Η), 7.94 (d, J = 8 Hz, 1Η), 7.48 -7.22 (m, 8H), 6.99 (s, 2H), 4.69 (t, J = 7 Hz, 1H), 3.55 (s, 3H), 3.27 and 3.22 (two overlapping dd, J = 6, 13 Hz, 2H ), 2.70-2.40 (complex m, ABX pattern, 4H), 2.38 (s, 3H), 1.53 (s, 3H), 1.10 and 1.09 (two overlapping triplets, J = 8 Hz, 6H); MS (+ APCI) : [M + H] +, 523. Step 2 (21〇-2-1 ~ 4- (2.3- 二甲某-着骈「2.3 41- 蹿望 -4 _ 基） ____- 2 · 6 _Diethyl benzyl chloride 1 ~ 3 ~ Phenylpropionic acid 4 Example 9 The method of step 7 is obtained from (2 R)-2 _ [4-(2,3 -dimethyl-fluorene [2, 3-b ] -Blann-4-yl) -2,6-diethylphenoxy] -3-phenylpropanoic acid methyl ester ((K46 g, 0.88 mmol), K0Η solution (1.1 ml of 1 »Solution, 1" millimolar), tetrahydrofuran (12.6 ml), and sufficient amount of methanol to prepare a homogeneous solution containing the title compound as a white solid (0.43 g-1 4 6 ~ This paper size applies to Chinese national standards (CNS ) A4 size (210 X 297 mm) (Please read the notes on the back before filling out this page) i Order --------- Line_ 510900 A7 B7 V. Description of the invention (ιβ) 89%): NMR (DMSO-d6): δ 12.91 (brs, 1H), 8.44 (s, 1H), 7.94 (d, J = 8 Hz, 1H), (Please read the notes on the back before filling this page) 7.47-7.22 (m, 8H), 6.98 (s, 2H), 4.61 (t $ J = 7 Hz, 1H), 3.25 (d, J = 7 Hz, 2H), 2.72 (complex m, ABX pattern, 1H), 2.66 ( Double β quartets, J = 8 Hz, 2H), 2.55 (complex m, ABX pattern, 1H), 2.38 (s, 3H), 1.55 (s, 3H), 1.10 and 1.09 (double llg triplets, J = 8 Hz, 6H); MS (-ESI): [MH] ·, 507; Anal. Calc, for C33H3203S0.6H2O: C, 76.30, H, 6.44, N, 0.00. Found: C, 76.44, H, 6.49, N, 0.04. Example 68 {(2R) -2- 「4- (2 · 3-Er Shenmou-Sai 骈 "2, 3: bl j Chamber-Pan-4-Li" _ j, fi-Eryou Qi a certain dogwood sucralose 1 acetic acid model 63 method From (2R} -2- [4- (2,3-dimethyl-naphthalenepyrene [2, 3-b] -blaze-4-yl) -2, 6-diethylphenylchloro] -3 -Phenylpropionic acid (0.27 g, (K53 mmol), chlorchloride (0.046 ml, 0.53 mmol), Ν, Ν-dimethylformamide (2 drops), benzene ( 9 ml), ethyl glycine hydrochloride (fl. 18 g, 1.0 mmol) and potassium sulfonate (0.46 g, 3.33 mmol), a solid was obtained at room temperature , Adsorbed to silica gel, and chromatographed with hexane: ethyl acetate (9Π: 10). The obtained solid (G.18 g) was treated with KOH solution (2.34 ml of 1 N solution, 2.34 mmol), tetrahydrofuran (10 ml), and sufficient methanol to prepare a homogeneous solution. The title compound was obtained as a pale yellow solid (0 η 10 g, 33%): NMR (DMSO-d6): δ 12.52 (br s, 1Η), 8.48 (t, J = 6 Ηζ, intellectual property of the Ministry of Economic Affairs Printed by the Bureau ’s Consumer Cooperatives 1Η), 8.43 (s, 1Η), 7.94 (d, J = 8 Ηζ, 1Η), 7.48-7.16 (m, 8Η), 6.93 (s, 2Η), 4.73 ( t, J = 7 Hz, 1H), 3.79 and 3.73 (double || dd, J = 6, 17 Hz, 2H), 3.24 (dd, J = 7, 14 Hz, 1H), 3.15 (dd, J = 7, 14 Hz, 1H), 2.80-2.50 (complex m, ABX pattern, 4H)), 2.39 (s, 3H), 1.56 (s, 3H), 1.07 (t, J = 8 Hz, 6H); MS ( + APCI): [M + H] +, 566; Anal. Calc, for C35H35N04S: C, 74.31, H, 6.24, N, 2.48. Found: C, 74.11, H, 6.69, N, 2.24 147- this paper Standards are applicable to China National Standard (CNS) A4 specifications (210 X 297 mm). Printed clothing for employees' cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7_ V. Description of invention (ι4) Example 69 4 1_ (2 4 —_3 ~ 2 Shenmou-support Win __ 「2, Nan-4-some） ~ 2« 6-Diethylphenol step] (2 -Zhong some-4, 5 -Dimethyl thio-3-Some)-(4 -Shen hydrogen some -3 5-Diethyl Ethyl) -Shenhao The method of step 49 of Example 49 consists of 3,5-diethyl-p-dinolide acid (1 0 · 6 6 g, 5 1 · 2 mmol) ; According to three steps, from 4-bromo-2, 6-diethylaniline and J. L i P owitz and T · C ohe II, J · 0 rg · C he ro · 1 9 6 5, 30, 3891-3894; CKBradsher.WA; J.Aro.Chem.Soc. 1 9 5 4, 76, 2 3 5 7-2 3 6 2; J. Alexander, 0 r g. Prep.

Proced. lot., 1986， 18， 2213-2215方法製得），草_氯（4 · 9毫升，5 6 · 2毫莫耳），N，N -二甲基甲醱胺 (2滴），2 , 3 _二甲基-5 -苄呋喃（1 1 · 4克，6 1 . 2毫莫耳），氯化錫（IV) ( 6.6毫升，56·4毫莫耳），及無水二氯甲烷（1 9 8毫升），可製得標題化合物之油（2 2 克，>10 0%) ， (DMS0-d6)：(5 7.42(s,2H),7.29-7.21(ffli, 3H),7.04(d,J=7Hz,2H),3.82(s,2H),3.74(s,3H),2.61 (quartet,J = 8Hz,4H) ,2. 19(s,3H) ,1.83(s,3H) ,1.13(t, J = 8 H z , 6 H ) 〇步驟2 4 - ( 2 . 3 -二申某-養駢f 2 . 3 - b 1-眹醸-4 -某）-2 ,6_二乙》仿例4 9步驟2之方法，由（2 -苄基-4，5 -二甲呋喃-3 -基） -（4 -甲氯基-3，5 -二乙苯基）-甲顚）（2 2克），三溴化硼（3 6 · 8 毫升，3 8 9毫莫耳），及二氯甲烷（〗8 0毫升），回流4小時 -1 4 8 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) i 訂---------線· 經濟部智慧財產局員工消費合作社印製 510900 A7 B7 五、發明說明）可製得標題化合物之摻白色固體（3 . 0 9克，17.5%)(0^0- d6): 6 8.29 (s, 1H), 7.96 (d, J = 8 Hz, 1H), 7.90 (s, 1H), 7.57 (d, J = 8 Hz, 1H), 7.39 (ddd, J = 1, 7, 8 Hz, 1H), 7.29 (ddd, J = 1, 7, 8 Hz, 1H), 6.89 (s, 1H), 2.75-2.55 (complex m, ABX pattern, 4H), 2.36 (s, 3H), 1.55 (s, 3H), 1.15 (t, J = 8 Hz, 6H); MS(EI): [M+] 344; Anal. Calc. For C24H2402: C, 83.69, H, 7.02, N, 0.00. Found: C, 82.53, H, 7.11, N, 0.05. 例70 (R) - 2 - f 4 - ( 9 -漳-2 , 3 -二甲某-養酣 Γ 2 , 3 - b Ί -映喃 ~~ 4 -基)______~ 2 . β-:二乙苯氣某嫌苯丙酸步驟1乙酿4 - ( 9 -海- 2 , 3 -二申某-暴駢F 2 , 3 - b Ί -眹g南 - 4 -某）-2 > 6 -二乙茱 _ 仿例49步驟3之方法，由4-(2，3-二甲基-萘駢[2，3-b] -呋喃-4 -基）-2，6 -二乙酚（1 · 7 5克，5 · 1毫莫耳），乙酐（〇 · 6 2毫升，6 · 6毫莫耳），及Pft聢（1 0 . 2毫升）可得固體（2· 23克），其可不經純化而使用^ 仿例4 9步驟4之方法，由乙酸4 - ( 2，3 -二甲基-萘駢[2，3 - I)]-呋喃-4 -基）-2，6 -二乙基-苯酯（2 · 2 3 克，5·8毫莫耳氯化鐵（ 2 4 7毫克，0.29毫莫耳），溴（〇· 34毫升，6· 4毫莫耳）及二氯甲烷（58毫升）Proced. Lot., 1986, 18, 2213-2215), grass_chlorine (4.9 ml, 56.2 mmol), N, N-dimethylformamide (2 drops), 2, 3_dimethyl-5 -benzylfuran (1 1.4 g, 6 1.2 mmol), tin (IV) chloride (6.6 ml, 56.4 mmol), and anhydrous dichloride Methane (198 ml) to obtain the title compound as an oil (22 g, > 100%), (DMS0-d6): (5 7.42 (s, 2H), 7.29-7.21 (ffli, 3H) , 7.04 (d, J = 7Hz, 2H), 3.82 (s, 2H), 3.74 (s, 3H), 2.61 (quartet, J = 8Hz, 4H), 2. 19 (s, 3H), 1.83 (s, 3H), 1.13 (t, J = 8 Hz, 6H) 〇 Step 2 4-(2.3-Ershenmou-raising 骈 f 2. 3-b 1- 眹醸 -4-awom) -2, 6_Diethyl "Example 4 9 The method of step 2 consists of (2-benzyl-4,5-dimethylfuran-3 -yl)-(4-methylchloro-3,5-diethylphenyl) -Formamidine (22 g), Boron tribromide (36. 8 ml, 3 89 mmol), and dichloromethane (80 ml), reflux for 4 hours-1 4 8-this paper Standards are applicable to China National Standard (CNS) A4 (210 X 297 mm) (Please read the precautions on the back before filling this page) i Order -------- -Line · Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7 V. Description of the invention) The title compound can be obtained with a white solid (3.09 g, 17.5%) (0 ^ 0-d6): 6 8.29 (s, 1H), 7.96 (d, J = 8 Hz, 1H), 7.90 (s, 1H), 7.57 (d, J = 8 Hz, 1H), 7.39 (ddd, J = 1, 7, 8 Hz, 1H), 7.29 (ddd, J = 1, 7, 8 Hz, 1H), 6.89 (s, 1H), 2.75-2.55 (complex m, ABX pattern, 4H), 2.36 (s, 3H), 1.55 (s, 3H), 1.15 (t, J = 8 Hz, 6H); MS (EI): [M +] 344; Anal. Calc. For C24H2402: C, 83.69, H, 7.02, N, 0.00. Found: C, 82.53, H, 7.11, N, 0.05. Example 70 (R)-2-f 4-(9 -Zhang-2, 3 -Dimethyl-Yangyang Γ 2, 3-b Ί-Eingan ~~ 4 -base) ______ ~ 2. Β-: Diethylbenzene gas Some benzene propionic acid Step 1 Ethanol 4-(9 -Sea-2, 3 -Di Shenmou-Storm F 2, 3-b Ί -Ίg 南-4 -A) -2 > 6-Diethyl ruthenium_ The method of step 3 of Example 49 is based on 4- (2,3-dimethyl-naphthalenepyrene [2,3-b] -furan-4 -yl)- 2,6-diethylphenol (1.75 g, 5.1 mmol), acetic anhydride (0.62 ml, 6.6 mmol), and Pft 聢 (10.2 ml) can Get solid (2 · 23 g), which can be used without purification ^ Example 4 9 Step 4 method from acetic acid 4-(2,3-dimethyl-naphthalene [2,3-I)]-furan-4 -yl) -2,6-diethyl-phenyl ester (2.23 g, 5.8 mmol of ferric chloride (247 mg, 0.29 mmol)), bromine (0.34 ml, 6.4 mmol) Moore) and dichloromethane (58 ml)

可製得標題化合物之固體（0 · 29克，10%) : N MR (DMSO-d6): δ 8.26 (d, J = 8 Hz, 1H), 7.64 (ddd, J = 1, 7, 8 Hz, 1H), 7.59 (d, J = 9The title compound was obtained as a solid (0.29 g, 10%): N MR (DMSO-d6): δ 8.26 (d, J = 8 Hz, 1H), 7.64 (ddd, J = 1, 7, 8 Hz , 1H), 7.59 (d, J = 9

Hz, 1H), 7.48 (ddd, J = 1, 7, 8 Hz, 1 H), 7.16 (s, 2H), 2.54 and 2.53 ( 二重鲞 quartets, J = 7 Hz, 4H), 2.44 (s, 3H), 2.42 (s, 3H), 1.54 (s, 3H), 1.14 (t, J = 7 Hz, 6H); MS(EI): [M+], 1 溴同位素式樣，464/466. J=7 Hz，6H); MS(EI): [M+]，l 溴同位素式樣，464/466。步驟2 4 - ( 9 — ?尊一 2 · 3 一二甲某-藜駢「2 · 3 - h Ί擊P南-4 一 -149- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7_ 五、發明說明二仿例4 9步驟5之方法，由乙酸4 - ( 9 -溴-2，3 -二甲基-萘駢[2，3 - b卜呋喃-4 -基）-2，6 -二乙苯酯（0 · 2 9克， 0.62毫莫耳），Κ0Η溶液（G.75毫升之1N溶液，0.75毫莫耳），四氫呋喃（8 · 9毫升），及足量甲醇可得含檫題化合物固體（〇 . 2 6克，1 0 0 % )之均質溶液：N M R ( D M S 0 - d6): δ 8.36 (s, 1H), 8.21 (d, J = 8 Hz, 1H), 7.63 (d, J = 8 Hz, 1H), 7.59 (ddd, J = 1, 7, 8 Hz, 1H), 7.41 (ddd, J = 1, 7, 8 Hz, 1H), 6.91 (s, 2H), 2.69 and 2.62 ( 二重叠 quartets, J = 7 Hz, 4H), 2.41 (s, 3H)，1.55 (s，3H), 1.14 (t，J = 7 Hz， 6 H ) ; M S ( E I ) : [ M + ]，1 溴同位素式樣 4 2 2 / 4 2 4。步驟 3 ( 2R) 一 2 -「4- (9 一》奪一 2. 3-二甲甚-赛駢「2* 3-bl -眹_ - 4 -某）-2 . 6 -二乙茱氩某1 Ί茉丙酴彷例4 9步驟6之方法，由4 - ( 9 -溴-2，3 -二甲基-萘駢 [2，3 - b ]-呋喃-4 -基）-2，6 -二乙酚（0 · 2 6 克，0 · 6 4 毫莫耳），（S) -2-羥基-3-苯丙酸甲酯（1 · 38克，7 · 66 毫莫耳三苯瞵（1.· 98克，7. 5 5毫莫耳），偶氮二羧酸二乙酯（〗· 2毫升，7 » 6 2毫莫耳）及無水苯（0 · 8 5毫升），於1 Q 0 °C下反應3 6小時可製得固體（0 · 1 5克，3 9 % ) ，其可不經純化而使用。仿例4 9步驟7之方法，由（2 R ) - 2 - [ 4 - ( 9 -溴-2，3 - 二甲基-萘駢[2，3 - b ]-呋喃-4 -基）-2，6 -二乙苯氣基] - 3 -苯丙酸甲酯（0 · 1 5克，0 · 2 5毫莫耳），K 0 Η溶液（0 · 9 8 毫升之1Ν溶液，0.98毫莫耳），四氫呋喃（2·5毫升），及足量甲醇可製得均質溶液其含檫題化合物白色固體 -1 5 0 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 510900 A7 ____B7 五、發明說明（^9) (0.1 g，71%): NMR (DMSO-d6): δ 12.95 (br s，1H)，8.23 (d, J = 8 Hz，1H), 7.66 (請先閱讀背面之注意事項再填寫本頁)Hz, 1H), 7.48 (ddd, J = 1, 7, 8 Hz, 1 H), 7.16 (s, 2H), 2.54 and 2.53 (double 鲞 quartets, J = 7 Hz, 4H), 2.44 (s, 3H), 2.42 (s, 3H), 1.54 (s, 3H), 1.14 (t, J = 7 Hz, 6H); MS (EI): [M +], 1 bromine isotope pattern, 464/466. J = 7 Hz, 6H); MS (EI): [M +], 1 Bromine isotope pattern, 464/466. Step 2 4-(9-? Zunyi 2 · 3 One two a certain-quinoa "2 · 3-h Tap P Nan-4--149- This paper size applies Chinese National Standard (CNS) A4 specifications (210 X 297 mm) -------------------- Order --------- line (Please read the precautions on the back before filling this page) Economy Printed by the Consumer Cooperatives of the Ministry of Intellectual Property Bureau 510900 A7 B7_ V. Description of the Invention 2 Method 4 9 Step 5 method using acetic acid b Bufuran-4-yl) -2,6-diethylphenyl ester (0.29 g, 0.62 mmol), K0Η solution (G.75 ml of 1N solution, 0.75 mmol), · 9 ml) and a sufficient amount of methanol to obtain a homogeneous solution containing the title compound solid (0.26 g, 100%): NMR (DMS 0-d6): δ 8.36 (s, 1H), 8.21 ( d, J = 8 Hz, 1H), 7.63 (d, J = 8 Hz, 1H), 7.59 (ddd, J = 1, 7, 8 Hz, 1H), 7.41 (ddd, J = 1, 7, 8 Hz , 1H), 6.91 (s, 2H), 2.69 and 2.62 (two overlapping quartets, J = 7 Hz, 4H), 2.41 (s, 3H), 1.55 (s, 3H), 1.14 (t, J = 7 Hz, 6 H); MS (EI): [M +], 1 bromine isotope Sample 4 2 2/4 2 4. Step 3 (2R) One 2-"4- (9 One" wins one 2. 3-Two even-Sai 骈 "2 * 3-bl-眹 _-4 -some) -2. 6-Diethylpyrrolium 1 1 Moprobramidine Example 4 9 The method of step 6 consists of 4-(9 -bromo-2,3-dimethyl-naphthalenepyrene [2,3-b]- Furan-4 -yl) -2,6-diethylphenol (0.26 g, 0.64 mmol), (S) methyl 2-hydroxy-3-phenylpropionate (1.38 g , 7.66 millimoles triphenylhydrazone (1. · 98 g, 7.55 millimoles), diethyl azodicarboxylate (2 · mL, 7 »62 millimoles) and anhydrous Benzene (0.85 ml) was reacted at 1 Q 0 ° C for 36 hours to obtain a solid (0.15 g, 39%), which can be used without purification. Example 4 9 Step 7 of Method by (2 R)-2-[4-(9 -Bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] -furan-4 -yl) -2,6-diethylbenzene Gas-based] methyl 3-phenylpropionate (0.15 g, 0.25 mmol), K 0 hydrazone solution (0.98 ml of 1N solution, 0.98 mmol), tetrahydrofuran (2 · 5 ml) and a sufficient amount of methanol to prepare a homogeneous solution containing the title compound as a white solid -1 5 0- Paper size applies to China National Standard (CNS) A4 (210 X 297 mm) -------------------- Order --------- Line ( Please read the notes on the back before filling this page) 510900 A7 ____B7 V. Description of the invention (^ 9) (0.1 g, 71%): NMR (DMSO-d6): δ 12.95 (br s, 1H), 8.23 (d , J = 8 Hz, 1H), 7.66 (Please read the precautions on the back before filling this page)

(m, 1H), 7.64-7.53 (m, 2H), 7.43-7.30 (m, 5H), 7.02 (s, 2H), 4.61 (t, J = 7 Hz, 1H), 3.25 (d, J = 7 Hz, 2H), 2.82-2.52 (complex m, ABX pattern, 4H), 2.41 (s, 3H), 1.49 (s，3H)，U1 and UO (二重叠 triplets, J = 7 Hz，6H); MS(-ESI): [ΜΗ]] 溴同位素式樣，569/571; Anal. Calc, for C33H31Br04: C, 69.35, H， 5.47, N, 0.00. Found: C, 69.93, H, 5.84, N, 0.19; Analytical HPLC 顯示主成分（9 8 . 3 )。例7 1 (R) -2-Γ2-擐戍某-4-（2一 3-二印某-棻_「2. 3 - b 1 -隍― 盼-4-某）-茱氩某1-丙_ 步驟 1 (2R)-2-「2 -瑗）戈某 _4 一（2.3 — 二申某一着· Γ 2 * 3 ~ b 1_ -ϋ拿盼-4-某）-茱氳甚1-丙酴申酯仿例49步驟6之方法，由2-環戊基-4- (2，3-二甲基-萘駢[2，3-b卜瞎吩-4-基）-酚（0·80克，2·2毫莫耳），（S) -(-)-乳酸甲酯（(Κ 2 4克，3.3毫莫耳），三苯膦（0.84克， 3 · 2毫莫耳偶氮二羧酸二乙酯（0 · 5 1毫升，3 2毫莫耳）及無水苯（5毫升），於9 G°C下反應可製得標題化合物之白色固體（〇 · 6 ?克，6 8 % :熔點6 5〜6 6 °C ·♦ N M R ( D M S 0 d6): δ 8.46 (s, 1H), 7.96 (d, J = 8 Hz, 1H), 7.50-7.30 (m, 3H), 7.14 (m, 1H), 7.09 經濟部智慧財產局員工消費合作社印製 and 7.08 (two dd，J = 2, 8 Hz，直生異構物，1H)，6.95 and 6.92 (two d，J = 8 Hz，直生異構物，1H), 5· 14 and 5.11 (two quartets, J = 7 Hz，直生異構物，1H), 3,75 and 3·70 (two s,直生異構物、3H), 3·43 (m, 1H)，2·41 (s，3H)，2.00 (m, 2H), 1.77-1.50 (m 含一雙線（J = 7 Hz) at δ 1·61 and a singlet at δ 1·57, 12H); MS(EI): [M+], 458; Anal. Calc, for C29H30O3S: C, 75.95, H, 6.59, N, 0.00. Found: C, 74.93, H, 6.55, N, -0.09. 步驟2 ( 2 R ) - 2 - F 2 -璟戍某-4 - ( 2 · 3 -二申某-赛駢「2 , 3二上丄 -1 5 1 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 510900 A7 _____κι___ 五、發明說明（（奸） (請先閱讀背面之注意事項再填寫本頁) 二唆—盼-4 -甚）-茱氤某丙酴仿例49步驟7之方法，由（2R)-2-[2-璟戊基-4-(2, 3-二甲基-萘駢[2, 3- b卜瞎盼-4-基卜苯氧基卜丙酸甲酯（〇·6 克，U毫莫耳），Κ0Η溶液（1·98毫升之IN溶液，1.98毫莫耳），四氫呋喃（9毫升），及甲醇（3毫升）可製得標題化合物白色固體（0.55克，95%):0pt.Rot.[a]25/D=+7.95° (10·068) mg/mL, MeOH); NMR (DMSO-d6): δ 13Ό2 (br s, 1H), 8.46 (s, 1H), 7.96 (d, J = 8(m, 1H), 7.64-7.53 (m, 2H), 7.43-7.30 (m, 5H), 7.02 (s, 2H), 4.61 (t, J = 7 Hz, 1H), 3.25 (d, J = 7 Hz, 2H), 2.82-2.52 (complex m, ABX pattern, 4H), 2.41 (s, 3H), 1.49 (s, 3H), U1 and UO (two overlapping triplets, J = 7 Hz, 6H); MS ( -ESI): [ΜΗ]] Bromine isotope pattern, 569/571; Anal. Calc, for C33H31Br04: C, 69.35, H, 5.47, N, 0.00. Found: C, 69.93, H, 5.84, N, 0.19; Analytical HPLC showed the main component (98.3). Example 7 1 (R) -2-Γ2- 擐戍某 -4- (2 一 3- 二印某-棻 _ 「2. 3-b 1-隍 ― hope-4-some）- C_ Step 1 (2R) -2- 「2-瑗） Gemou _4 One (2.3 — Two Shenmou · Γ 2 * 3 ~ b 1_ -ϋNapan-4-) -Propionate ester method 49 step 6 method, from 2-cyclopentyl-4- (2,3-dimethyl-naphthalene [2,3-b buphenphen-4-yl)-phenol ( 0.80 g, 2.2 mmoles, (S)-(-)-methyl lactate ((K 2 4 g, 3.3 mmoles), triphenylphosphine (0.84 g, 3.2 mmoles) Diethyl azodicarboxylate (0.51 ml, 32 mmol) and anhydrous benzene (5 ml) were reacted at 9 G ° C to obtain the title compound as a white solid (0.66 g , 6 8%: melting point 6 5 ~ 6 6 ° C · NMR (DMS 0 d6): δ 8.46 (s, 1H), 7.96 (d, J = 8 Hz, 1H), 7.50-7.30 (m, 3H) , 7.14 (m, 1H), 7.09 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs and 7.08 (two dd, J = 2, 8 Hz, orthoisomers, 1H), 6.95 and 6.92 (two d, J = 8 Hz, orthoisomer, 1H), 5. · 14 and 5.11 (two quartets, J = 7 Hz, orthoisomer, 1H), 3,75 and 3.70 (two s, orthoisomers, 3H), 3.43 (m, 1H), 2.41 (s, 3H), 2.00 (m, 2H), 1.77-1.50 (m with one double line (J = 7 Hz) at δ 1.61 and a singlet at δ 1.57, 12H); MS (EI): [M +], 458; Anal. Calc, for C29H30O3S: C, 75.95, H, 6.59, N , 0.00. Found: C, 74.93, H, 6.55, N, -0.09. Step 2 (2 R)-2-F 2-璟戍某 -4-(2 · 3-二申某-赛骈「2, 3 二上丄 -1 5 1-This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 510900 A7 _____ κι ___ 5. Description of the invention ((treasure) (Please read the precautions on the back before filling in this Page) Dioxin—Pan-4—even) -Fructus Corni, a Propionate Example 49, Method of Step 7 from (2R) -2- [2-Pentyl-4- (2, 3-dimethyl- Naphthalene hydrazine [2, 3-b blazepan-4-yl phenoxypropionate methyl ester (0.6 g, U mol), KO solution (1.98 ml of IN solution, 1.98 mM Ear), tetrahydrofuran (9 ml), and methanol (3 ml) to obtain the title compound as a white solid (0.55 g, 95%): 0pt.Rot. [A] 25 / D = + 7.95 ° (10 · 068) mg / mL, MeOH); NMR (DMSO-d6): δ 13Ό2 (br s, 1H), 8. 46 (s, 1H), 7.96 (d, J = 8

Hz, 1H), 7.50-7.30 (m, 3H), 7.13 and 7.12 (two doublets, J = 2 Hz,直生異構物 1H)，7.11 and 7.09 (two dd，J = 2, 8 Hz,直生異構物乂1H)，6·93 and 6.91 (two doublets，J = 8 Hz,直生異構物,1H)，4.95 (q，J = 7 Hz，1H)，3.44 (m，1H)，2·41 (s，3H)，2·00 (m，2H)，1.79-1.50 (m 含一單線在（J = 7 Hz) at δ 1.60 and aHz, 1H), 7.50-7.30 (m, 3H), 7.13 and 7.12 (two doublets, J = 2 Hz, orthoisomer 1H), 7.11 and 7.09 (two dd, J = 2, 8 Hz, orthodontic Isomers 乂 1H), 6.93 and 6.91 (two doublets, J = 8 Hz, orthoisomer, 1H), 4.95 (q, J = 7 Hz, 1H), 3.44 (m, 1H), 2 · 41 (s, 3H), 2.00 (m, 2H), 1.79-1.50 (m with a single line at (J = 7 Hz) at δ 1.60 and a

singlet at δ 1.58, 12H); MS(EI): [M+]，444; Anal. Calc, for C28H2803S: C，75.64, H, 635, N, 0.00. Found: C, 74.10, H, 6.32, N,-0.09; Analytical HPLC 顯示主成分9 9 · 9 9 % )。例72 (R ) - 2 - U - ( 9 -湟-2 · 3 -二甲某-赛駢 Γ 2 . 3 - h 1 - Pf 盼-4- 某）-2 -璟1¾某-茱氩某1-丙麟仿例49步驟6之方法，由2-璟戊基-4- ( 9-溴-2，3-二甲基-萘駢[2, 3-b卜睹盼-4-基）-酚（0.37克，0.99毫莫耳），（S) _ ( -乳酸甲酯（0 · 75克，7 · 9毫莫耳）經濟部智慧財產局員工消費合作社印制衣，三苯_( 2 · 1克，8 · 0毫莫耳），偶氮二羧酸二乙酯 (1 · 2 3毫升，7 · 8毫奠耳）及無水苯（1 · 〇毫升），於9 〇 X；下反應1 8小時可製得標題化合物之固體（0 · 2克，2 8 % ) ，其可不經純化而使用。彷例4 9步驟7之方法，由（2 R ) - 2 - [ 4 - ( 9 -溴-2，3 - -152- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） — 510900 A7 ________ B7 五、發明說明（d) 二甲基-蔡駢[2，3- b卜睹吩-4-基）_2_環戊基-苯氯基】 -丙酸甲酯（〇·2克，〇·37毫莫耳），KOH溶液（0·7 4毫升之1Ν溶液，0.74毫莫耳），四氫呋喃（3.7毫升），及足量甲醇可製得含檫題化合物摻白色固體（〇 · i 8克，9 5 X ) 均質溶液：NMR(DMSO-d6): δ 13.00(br s，1H)，8.18 (d，J = 8 Hz, 1H), 7·63 (m，1H)，7.50-7.40 (m, 2H), 7.14 and 7· 13 (two doublets，J = 2 Hz，直生異構物，1H)，7·10 and 7.09 (two dd，J = 2,8 Hz,直生異構物· 1H)，6.93 and 6·91 (twodoublets, J = 8Hz,直生異構物，1H),4.94 (η, J = 7 Hz· IH)，3,41 (m· m). 2.42 (s, 3H), 1.98 (m, 2H), 1.78-1.46 (m 含二單線在 δ 1.59 and 1,58 (J = 7 Hz，直生異構物）and a singlet at δ 1.54, 12H); MS(-ESI): [M-H], 1 溴同位素式樣，521/523; Anal.Calc. forC28H27Br03S: C，64.24，H，5.20, N, 0.00. Found: C, 64.11, H, 5.52, N, 0.10. 例 4 '[A:—m -2· 3 -二甲某-寨駢 l~2· 3 - hl-Pt 盼-4 -某、 -2 -環戍某-荣氩某1- 丁酴singlet at δ 1.58, 12H); MS (EI): [M +], 444; Anal. Calc, for C28H2803S: C, 75.64, H, 635, N, 0.00. Found: C, 74.10, H, 6.32, N, -0.09; Analytical HPLC showed the main component 9 9 · 9 9%). Example 72 (R)-2-U-(9-湟 -2 · 3 -Dimethyl -1-Sai 骈 Γ 2. 3-h 1-Pf Pan-4-)) -2-璟 1 ¾-Ju Zhu The method of step 6 of 1-propylimine Example 49 is based on 2-fluorenyl-4- (9-bromo-2,3-dimethyl-naphthalenefluorene [2, 3-b -Phenol (0.37 g, 0.99 mmol), (S) _ (-Methyl lactate (0.75 g, 7.9 mmol) Printed clothing by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, Triphenyl_ ( 2.1 g, 8.0 mmol), diethyl azodicarboxylate (1.23 ml, 7.8 mmol) and anhydrous benzene (1.0 ml) at 90 ° C; The reaction was carried out for 18 hours to obtain the title compound as a solid (0.2 g, 28%), which was used without purification. Example 4 9 The method of step 7 was obtained from (2 R)-2-[4- (9 -Bromo-2,3--152- This paper size is applicable to Chinese National Standard (CNS) A4 (210 X 297 mm) — 510900 A7 ________ B7 V. Description of the invention (d) Dimethyl-Cai Yue [ 2,3-b phen-4-yl) _2-cyclopentyl-phenylchloro]-methyl propionate (0.2 g, 0.37 mmol), KOH solution (0.7 4 ml 1N solution, 0.74 Moore), tetrahydrofuran (3.7 ml), and sufficient amount of methanol to prepare a title compound containing a doped white solid (0.88 g, 9 5 X). Homogeneous solution: NMR (DMSO-d6): δ 13.00 (br s , 1H), 8.18 (d, J = 8 Hz, 1H), 7.63 (m, 1H), 7.50-7.40 (m, 2H), 7.14 and 7. · 13 (two doublets, J = 2 Hz, straight Isomers, 1H), 7.10 and 7.09 (two dd, J = 2,8 Hz, orthoisomer 1H), 6.93 and 6.91 (twodoublets, J = 8Hz, orthoisomer, 1H), 4.94 (η, J = 7 Hz · IH), 3,41 (m · m). 2.42 (s, 3H), 1.98 (m, 2H), 1.78-1.46 (m with two single wires in δ 1.59 and 1,58 (J = 7 Hz, orthoisomers) and a singlet at δ 1.54, 12H); MS (-ESI): [MH], 1 bromine isotope pattern, 521/523; Anal.Calc. For C28H27Br03S: C, 64.24, H, 5.20, N, 0.00. Found: C, 64.11, H, 5.52, N, 0.10. Example 4 '[A: —m -2 · 3-二甲某-寨骈 l ~ 2 · 3 -hl-Pt Pan-4-some, -2-cymbals-rong arg-1-ding

步驟 1 4_r—L4: ( 9 -海-？·. 2 -二申某-赛 _「2 . 3 - h 1- _ 盼-I 基）-2 -爝戍某-茱饈某1-丁酴申酯將2 -璟戊基-4 - ( 9 -溴-2，3 -二甲基-蔡駢[2，3 - b ]- 時盼-4 -基）-酚（〇 · 3 0克，0 · 8 1毫莫耳），4 -溴丁酸甲酯（】· 5毫升，1 3 · 0毫莫耳），6 0 % N a H ( G · 0 9克，2 · 3毫莫耳）Step 1 4_r—L4: (9 -Sea-? ·. 2 -Second-Mou-Sai_ 「2. 3-h 1- _Pan-I group） -2-爝戍 -Mandarin-Fructus 1-Butanate Add 2-pentylpentyl-4-(9 -bromo-2,3-dimethyl-Ceamidine [2,3-b]-sep-4 -yl) -phenol (0.30 g, 0 · 8 1 mol), methyl 4-bromobutyrate (] · 5 ml, 13 · 0 mol), 60% Na H (G · 0 9 g, 2.3 mol)

及磺酸鉀U · (1克，7 . 2毫奠耳）及無水苯（2毫升）加熱至10 fl°C 3 小時。層析以己烷/乙酸乙麵可製得標題化合物之固體 (0 · 2 3 克，5 2 % ) : δ 8.18 (d，J = 8 Ηζ，1Η)，7.62 (ddd，J = 2,6,8 Hzf 1Η)， 7.50-7.41 (m, 2H), 7.16-7.04 (m, 3H), 4.11 (m, 2H), 3.63 (s, 3H), 3.31 (quintet, J = 8 Hz, 1H), 2,57 (t, J = 7 Hz, 2H), 2.42 (s, 3H), 2.07 (quintet, J = 7 Hz, 2H), 1.95 -1 5 3 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) --II - I I I I 11111111 . 經濟部智慧財產局員工消費合作社印製經濟部智慧財產局員工消費合作社印製 510900 A7 / ' \ / _B7___ 五、發明說明（、P) (!11521〇51.74-1.4 5(1!1 含二單線 d 1.569H); MS(EI): [Μ +1溴同位素式樣，5 5 0 / 5 5 2。步驟 2 4 -「4 -___( 9 -淳-2 ,—3~二二甲某-養辦 Γ 2 ^ 3 - bl~ 嗦盼 ~4-某）-2 -環戍某-茱氤某Ί - 丁醱仿例4 9步驟7之方法，由4 - [ 4 - ( 9 -溴-2，3 -二甲基-萘駢[2，3 - b卜B塞盼-4 -基）-2 -璟戊基-苯氯基]-丁酸甲酯（123克，（K42毫莫耳），Κ0Η溶液（1·66毫升之1N 溶液，L 66毫莫耳），四氫呋喃（9 , 2毫升），及足量甲醇可製得含標題化合物摻白色固體（〇 . 2 2克，1 0 0 %) 均質溶液：NMR iDMSO· (0.22 g, 100%): NMR (DMSO-d6): δ 12.15 (br s, 1H), 8.18 (d, J = 8 Hz, 1H), 7.62 (ddd, J = 2,6,8 Hz, 1H), 7.51-7.41 (m, 2H), 7.14-7.05 (m, 3H), 4.10 (m, 2H), 3.37 (m, 1H), 2.48 (t, J = 7 Hz, 1H), 2.41 (s, 3H), 2.04 (quintet, J = 7 Hz, 2H), 1.96 (m, 2H)，1.72-1.44 (m 含一單線在 δ1.56,9Π); MS(-ESl)MM-nj，l 溴同位素式樣，535/537; Anal. Calc, for C29H29Br03S: C，64.80, H，5.44, N， 0.00. Found: C, 64.20, H, 5.50, N, 0.03. 例74 2 -環戊基-4 -( 2« 3'二甲某-養駢「2, 3-b卜喃-4 -某） -酚仿例49步驟1之方法，由3-環戊基-對-大菌香醇酸（10 克，4 5 s 4毫莫耳，R N - 5 9 2 1 6 - 8 2 - 9 )，草酸氯（4 · 4毫升 ,5 0 · 4毫莫耳），N， N -二甲基甲醯胺（2滴），2， 3 - 二甲基-5 -芣呋喃（1 0 · 1克，5 4 · 2毫莫耳），氯化錫（I V ) (5 · 8毫升，4 9 · 6毫莫耳），及無水二氯甲烷（1 8 3毫升）可製得油（1 8 · 8克），其可不經純化而使用。仿例4 9步驟2之方法，由（2 -苄基-4 , 5 -二甲呋喃 -1 5 4 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印制衣 510900 A7 B7_ 五、發明說明 -3 _基）-(3 _環戊基-4 -甲氧苯基）-甲酮（1 8 · 8克， 48 «4毫莫耳），三溴化聰（34 β 8毫升，3 6 8毫莫耳），及二氯甲烷（1 6 7毫升），於5 0 - 5 5 °C下反應2小時可製得標題化合物之淡棕色固體（1.56克，9.6%): (DMSO-d6): δ 9.46 (s, 1H), 7.96 (d, J = 8 Hz, 1H), 7.90 (s, 1H), 7.54 (d, J = 8 Hz, 1H), 7.39 (ddd, J = 1, 7, 8 Hz, 1H), 7.29 (ddd, J = 1, 7, 8 Hz, 1H), 7.04 (d, J = 2 Hz, 1H), 6.97 (dd, J = 2, 8 Hz, 2H), 6.91 (d, J = 8 Hz, 1H), 3.38-3.26 (m, 1H), 2.36(s，3H), 1.96 (m，2H), 1.74-1.44 (m 含一單線在 δ 1.55, 9H); MS(EI): [M+] 356; Anal. Calc, for C25H2402: C, 84.24, H, 6.79, N, 0.00. Found: C, 83.48, H, 6.71, N, 0.04 例75 乙_2-環戍某-4-(2,3-二甲某-赛_「2.3-1>1-眹_二4二某）-¾ _ 仿例4 9步驟3之方法，由2 -環戊基-4 - ( 2，3 -二甲基-蔡駢[2, 3-b卜呋喃-4-基卜酚（4. 8】克，13. 5毫莫耳），乙酐 (1 · 6 0毫升，1 7 „0毫莫耳），毗啶（2 7毫升）及二氯甲烷（2 7毫升）可製得産物，層析以己烷/乙酸乙酯可製得標題化合物之固體（0,92 克 5】7%):NMR(DMS0-d6):(y 8.00(d，J = 8Hz，lH)， 7.97 (s, 1H), 7.42 (ddd, J = 1, 7, 8 Hz, 1H), 7.34 (ddd, J = 1, 7, 8 Hz, 1H), 7.30 (d, J = 2 Hz, 1H), 7.22 (dd, J = 2, 8 Hz, 1H), 7.19 (d, J = 8 Hz, 1H), 3.14 (m, 1H), 2.37 (s, 3H), 2.36 (s, 3H), 1.96 (m, 2H), 1.74-1.44 (m 含一單線在 δ 1.52, 9H); MS(+ESI): [Μ+ΗΓ 399; Anal· Calc· for C27H2603: C，81.38, H，6·58, N， 0.00. Found: C, 80.76, H, 6.65, N, 0.05. 5.24, N, 0.03. 例76 (R ) _2~「4-__( 2 >__3~二甲基-養 fel i 2 « 3 - 瞎盼-4-基） -1 5 5 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 χ 297公釐） ---------I I I - I------訂--- ----I I (請先閱讀背面之注意事項再填寫本頁) 510900 A7 B7 五、發明說明（叫） -2二氳某1 - 3 -茉丙酴仿例4 9步驟6之方法，由2 —乙基_ 4 — ( 2， 3 _二甲基-萘 (請先閱讀背面之注意事項再填寫本頁) 駢[2，3-b卜晴盼-4-基）-酚（1β47克，4·42毫莫耳）， (S) -2-羥基-3_苯丙酸甲酯（4β78克，26·5毫莫耳），三苯麟（6·96克，26. 5毫莫耳），偶氮二羧酸二乙酯 (4·18毫升，26·5毫莫耳）及無水苯（8川毫升）可得固鎖，其可不經純化而使用。彷例4 9步驟7之方法，由（R ) - 2 - [ 4 - ( 2， 3 -二甲基 -萘駢[2，3-b]-瞎吩-4-基）-2-乙基-苯氣基】-3-苯丙酸甲_ (〇·16克，0·32毫莫耳），KOH溶液（0·65毫升之1Ν溶液，0.65毫莫耳），四氫呋喃（3· 2毫升），及足量甲醇可製得含檫題化合物黃色泡沫（0 . 1克，63%)均質溶液：NMR (DMSO-d6): δ 13.11 (br s，1Η)，8.43 (d，J = 2 Ηζ，1Η)，7,93 (dd，J =3, 8 Hz, 1H), 7.48-7.20 (m, 8H), 7.10-7.00 (m, 2H), 6.86 (dd, J = 4, 9 Hz, 1H), 5.08 and 5·04 (two dd, J = 4, 8 Hz,直生異構物，1H)，3·42 (m，ABX pattern，2H), 2.75-2.52 (complex m，ABX pattern，直生異構物，2H)，2.38 (s, 3H), 1·56 and 1.54 (two s,直生異構物，3H), 1.08 and 1.06 (two t，J = 7 Hz, 3H); MS(EI): [M+], 480; Anal. Calc, for C31H2803S: C, 77.47, H, 5.87, N, 0.00. Found: C, 74.55, H, 5.87, N, 0.20. 例” 經濟部智慧財產局員工消費合作社印製 (R ) - U -（ 9 -淳-?· ‘ 3 -二申某-赛駢— 某）7.甚-茶氩甚1 Ί茱丙酸步驟 1 7.酪 4 _(厂 3 -二申某-萘駢一1 二bJ二ΑΑ二^ ，-乙某_本醋仿例4 9步驟3之方法，由2 -乙基-4 - ( 2，3 -二甲基-蔡’駢 -1 5 8- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印製 510900 A7 B7_ 五、發明說明 [2 , 3-b卜瞟吩-4-基卜酚（1 · 4克，4 · 2毫莫耳），乙酐（fl · 52 毫升，5 . 5毫莫耳），及吡啶（8 · 4毫升）可製得産物，層析以己烷/乙酸乙酯可製得標題化合物之固體（1.62克， >100%): NMR (DMSO-d6): δ 8.49 (s, 1H), 7.97 (d, J = 9 Hz, 1H), 7.50-7.43 (m，1H)，7·40-7·35 (m, 2H), 7.27 (s，1H), 7.21 (s，2H), 2.57 (二重叠 quartets,J = 8 Hz, 2H), 2.40 (s, 3H), 2.37 (s, 3H), 1.58 (s, 3H), 1.13 (t, J = 8Hz, 3H); MS(EI): [M+]374; Anal. Calc, for C24H2202S: C, 76.97, H, 5.92, N, 0.00. Found: C, 75.72, H, 5.92, N, 0.03. 步驟2 乙 4 -（ 9 -海- 2 > 3 -二甲某-赛駢Γ 2 · 3 - b 1 -瞎盼 -4 _基)___-~2~乙某-篆酷仿例49步驟4之方法，由乙酸4- ( 2，3-二甲基-禁駢[2，3-b卜時吩-4-基）-2-乙基-苯_ (1·53克， 4 s 1毫莫耳），氯化鐵（4 1毫克，0 · 2 2毫莫耳），溴 (0·23毫升，4·5毫莫耳）及二氯甲烷（35毫升）可And potassium sulfonate U · (1 g, 7.2 millimoles) and anhydrous benzene (2 ml) are heated to 10 fl ° C for 3 hours. Chromatography with hexane / ethyl acetate gave the title compound as a solid (0.23 g, 52%): δ 8.18 (d, J = 8 Ηζ, 1Η), 7.62 (ddd, J = 2,6 , 8 Hzf 1Η), 7.50-7.41 (m, 2H), 7.16-7.04 (m, 3H), 4.11 (m, 2H), 3.63 (s, 3H), 3.31 (quintet, J = 8 Hz, 1H), 2,57 (t, J = 7 Hz, 2H), 2.42 (s, 3H), 2.07 (quintet, J = 7 Hz, 2H), 1.95 -1 5 3-This paper size applies to Chinese National Standard (CNS) A4 Specifications (210 X 297 mm) (Please read the notes on the back before filling out this page) --II-IIII 11111111. Printed by the Consumers ’Cooperative of the Intellectual Property Bureau of the Ministry of Economy Printed by the Employee ’s Cooperative of the Intellectual Property Bureau of the Ministry of Economy 510900 A7 / '\ / _B7___ V. Description of the invention (, P) (! 11521〇51.74-1.4 5 (1! 1 with two single lines d 1.569H); MS (EI): [Μ +1 bromine isotope pattern, 5 5 0 / 5 5 2. Step 2 4-"4 -___ (9 -Chun-2, -3 ~ two dimethyl a-raise Γ 2 ^ 3-bl ~ 嗦盼 ~ 4- 某)-2-戍-- Cornus officinalis-Ding 酦酦 Example 4 9 The method of step 7 consists of 4-[4-(9 -bromo-2,3-dimethyl-naphthalene 骈 [2,3 -b BB 塞潘 -4- ) -2 -Pentamyl-phenylchloro] -butane Methyl ester (123 g, (K42 mmol), K0Η solution (1.66 ml of a 1N solution, L 66 mmol), tetrahydrofuran (9.2 ml), and a sufficient amount of methanol can be prepared to contain the title compound. White solid (0.22 g, 100%) Homogeneous solution: NMR iDMSO · (0.22 g, 100%): NMR (DMSO-d6): δ 12.15 (br s, 1H), 8.18 (d, J = 8 Hz, 1H), 7.62 (ddd, J = 2,6,8 Hz, 1H), 7.51-7.41 (m, 2H), 7.14-7.05 (m, 3H), 4.10 (m, 2H), 3.37 (m , 1H), 2.48 (t, J = 7 Hz, 1H), 2.41 (s, 3H), 2.04 (quintet, J = 7 Hz, 2H), 1.96 (m, 2H), 1.72-1.44 (m with a single line At δ1.56,9Π); MS (-ESl) MM-nj, l bromoisotope pattern, 535/537; Anal. Calc, for C29H29Br03S: C, 64.80, H, 5.44, N, 0.00. Found: C, 64.20 , H, 5.50, N, 0.03. Example 74 2 -Cyclopentyl-4-(2 «3 'dimethyl--骈" 2,3 -b-furan-4--)-phenol Example 49 Step 1 The method consists of 3-cyclopentyl-p-mycobacteric acid (10 g, 4 5 s 4 mmol, RN-5 9 2 1 6-8 2-9), chlorine oxalate (4.4 ml, 5 0 · 4 mmol), N, N -dimethylformamide (2 drops), 2, 3 -dimethyl-5 -fluorene Murmur (10 · 1 g, 5 4 · 2 mmol), tin (IV) chloride (5 · 8 ml, 4 9 · 6 mmol), and anhydrous methylene chloride (1 8 3 ml) can An oil (18. 8 g) was obtained, which was used without purification. The method of step 4 of 9 in Example 4 is from (2-benzyl-4, 5 -dimethylfuran-1 5 4-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) --- ----------------- Order --------- line (please read the notes on the back before filling out this page) Clothing 510900 A7 B7_ V. Description of the Invention -3 -yl)-(3 _cyclopentyl-4 -methoxyphenyl) -methanone (18.8 g, 48 «4 mmol), tribromide Satoshi (34 β 8 ml, 368 mmol) and methylene chloride (167 ml) were reacted at 50-55 ° C for 2 hours to obtain the title compound as a light brown solid (1.56 g , 9.6%): (DMSO-d6): δ 9.46 (s, 1H), 7.96 (d, J = 8 Hz, 1H), 7.90 (s, 1H), 7.54 (d, J = 8 Hz, 1H), 7.39 (ddd, J = 1, 7, 8 Hz, 1H), 7.29 (ddd, J = 1, 7, 8 Hz, 1H), 7.04 (d, J = 2 Hz, 1H), 6.97 (dd, J = 2, 8 Hz, 2H), 6.91 (d, J = 8 Hz, 1H), 3.38-3.26 (m, 1H), 2.36 (s, 3H), 1.96 (m, 2H), 1.74-1.44 (m includes one Single line at δ 1.55, 9H); MS (EI): [M +] 356; Anal. Calc, for C25H2402: C, 84.24, H, 6.79, N, 0.00. Found: C, 83 .48, H, 6.71, N, 0.04 Example 75 B_2_Cyclium-4- (2,3-Dimethylx-Sai_ 「2.3-1 > 1- 眹 _ 二 4 二某） -¾ _ The method of step 4 9 of Example 4 was carried out from 2-cyclopentyl-4-(2,3-dimethyl-Ceamidine [2, 3-b bufuran-4-ylbuphenol (4.8) g, 13.5 mmol), acetic anhydride (1.60 ml, 17 „0 mmol), pyridine (27 ml) and dichloromethane (27 ml) can be prepared by chromatography. Hexane / ethyl acetate gave the title compound as a solid (0,92 g, 5] 7%): NMR (DMS0-d6): (y 8.00 (d, J = 8Hz, 1H), 7.97 (s, 1H) , 7.42 (ddd, J = 1, 7, 8 Hz, 1H), 7.34 (ddd, J = 1, 7, 8 Hz, 1H), 7.30 (d, J = 2 Hz, 1H), 7.22 (dd, J = 2, 8 Hz, 1H), 7.19 (d, J = 8 Hz, 1H), 3.14 (m, 1H), 2.37 (s, 3H), 2.36 (s, 3H), 1.96 (m, 2H), 1.74 -1.44 (m with a single line at δ 1.52, 9H); MS (+ ESI): [Μ + ΗΓ 399; Anal · Calc · for C27H2603: C, 81.38, H, 6.58, N, 0.00. Found: C , 80.76, H, 6.65, N, 0.05. 5.24, N, 0.03. Example 76 (R) _2 ~ 「4 -__ (2 > __ 3 ~ dimethyl-supported fel i 2« 3-blind hope-4- Base) -1 5 5-This paper size applies to Chinese national standards ( CNS) A4 specification (210 χ 297 mm) --------- III-I ------ Order ------- II (Please read the precautions on the back before filling this page ) 510900 A7 B7 V. Description of the invention (called) -2 Dioxin 1-3-Moprosin Example 4 9 The method of step 6 consists of 2 -ethyl_ 4-(2, 3_dimethyl-naphthalene (Please read the notes on the back before filling this page) 骈 [2,3-b Bu Qingpan-4-yl) -phenol (1β47 g, 4.42 mmol), (S) -2-hydroxy- Methyl 3-phenylpropionate (4β78 g, 26.5 mmol), triphenylline (6.96 g, 26.5 mmol), diethyl azodicarboxylate (4.18 ml, 26.5 mmol) and anhydrous benzene (8 mL) can be obtained as a lock, which can be used without purification. The method of Step 4 9 of Example 4 was performed by (R)-2-[4-(2, 3 -dimethyl-naphthalenepyrene [2,3-b] -benzophen-4-yl) -2-ethyl -Benzoyl] -3-phenylpropanoic acid methyl formaldehyde (0.16 g, 0.32 mmol), KOH solution (0.65 ml of 1N solution, 0.65 mmol), tetrahydrofuran (3.2 ml ), And a sufficient amount of methanol to prepare a yellow foam (0.1 g, 63%) homogeneous solution containing the title compound: NMR (DMSO-d6): δ 13.11 (br s, 1Η), 8.43 (d, J = 2 Ηζ, 1Η), 7,93 (dd, J = 3, 8 Hz, 1H), 7.48-7.20 (m, 8H), 7.10-7.00 (m, 2H), 6.86 (dd, J = 4, 9 Hz, 1H), 5.08 and 5.04 (two dd, J = 4, 8 Hz, orthoisomer, 1H), 3.42 (m, ABX pattern, 2H), 2.75-2.52 (complex m, ABX pattern, Orthoisomers, 2H), 2.38 (s, 3H), 1.56 and 1.54 (two s, orthoisomers, 3H), 1.08 and 1.06 (two t, J = 7 Hz, 3H); MS (EI): [M +], 480; Anal. Calc, for C31H2803S: C, 77.47, H, 5.87, N, 0.00. Found: C, 74.55, H, 5.87, N, 0.20. Example "Intellectual Property Bureau, Ministry of Economic Affairs Printed by the Employee Consumer Cooperative (R)-U-(9 -Chun-? · '3-二申某-赛骈 — XX) 7. Even- Argon 1 Dogwood Propionate Step 1 7. Case 4 _ (Plant 3-Di Shenmou-Naphthalene 骈 1 1 bJ Di ΑΑ Di ^,-B _ _ this vinegar model 4 9 Step 3 method, from 2 -Ethyl-4-(2,3 -dimethyl-Cai '骈 -1 5 8- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) Consumer Cooperative of Intellectual Property Bureau, Ministry of Economic Affairs Printed 510900 A7 B7_ V. Description of the invention [2, 3-b Buphenphen-4-ylbuphenol (1.4 g, 4.2 mmol), acetic anhydride (fl. 52 ml, 5.5 mmol) Mol), and pyridine (8.4 ml) to obtain the product. Chromatography with hexane / ethyl acetate gave the title compound as a solid (1.62 g, > 100%): NMR (DMSO-d6): δ 8.49 (s, 1H), 7.97 (d, J = 9 Hz, 1H), 7.50-7.43 (m, 1H), 7.40-7 · 35 (m, 2H), 7.27 (s, 1H), 7.21 (s, 2H), 2.57 (two overlapping quartets, J = 8 Hz, 2H), 2.40 (s, 3H), 2.37 (s, 3H), 1.58 (s, 3H), 1.13 (t, J = 8Hz, 3H ); MS (EI): [M +] 374; Anal. Calc, for C24H2202S: C, 76.97, H, 5.92, N, 0.00. Found: C, 75.72, H, 5.92, N, 0.03. Step 2 B 4- (9 -sea- 2 > 3 -dimethyla-sai 骈 Γ 2 · 3-b 1-盼望 -4 _base) ___- ~ 2 ~ Yumou- 篆 Cool Example 49 Step 4 method, from 4- (2,3-dimethyl-anhydroacetic acid [2,3-b 时时- 4-yl) -2-ethyl-benzene (1.53 g, 4 s 1 mmol), ferric chloride (41 mg, 0.2 2 mmol), bromine (0.23 ml, 4.5 mmol) and dichloromethane (35 ml)

製得標題化合物之固體（〇 · 4 8克，2 6 % ) ’· N M R (DMS0-d6): δ 8.21 (d, J = 9 Hz, 1H), 7.65 (ddd, J = 2, 6, 8 Hz, iH), 7.57-7.40 (m, 2H)，7·30 (s，1H), 7.23 (s，2H), 2.56 (二重叠 quartets, J = 8 Hz，2H)，2·43 (s, 3H), 2.37 (s, 3H), 1.56 (s, 3H), 1.13 (t, J = 8 Hz, 3H). 步驟 3 4 - ( 9-m - 2 . 3 H g I 一 M if 「2 · 3 - b 1 - m - 4 ~ 基)__m 仿例49步驟5之方法，由乙酸4 - (9-溴-2，3-二甲基-萘駢f 2，3 ~ b ] - P窜吩-4 -基）-2 -乙苯酷（1 · 5克，3 · 3毫莫耳）， K0H溶液（4 · 0毫升之1N溶液，4 · 0毫莫耳），四氫呋喃（55 毫升），及甲醇（3 7毫升）可得標題化合物之緣色泡沫（1 · 4 克，> 1 〇 fU ) : NMR (DMSOd6): δ 9.55 (s，1H)，8.16 (d，J = 9 Hz，1H)， 7.62 (ddd, J = 1, 7, 8 Hz, 1H), 7.54 (d, J = 8 Hz, 1H), 7.44 (ddd, J = 1, 7, 8 Hz, 1H), 7.05-6.87 (m, 3H), 2.60 (complex m, ABX pattern, 2H), 2.41 (s, 3H), 1.59 (s, 3H), 1.13 (t, J = 8 Hz, 3H). 457- 本紙張尺度適用中國國家標準（CNS)A4規格（210 x 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 510900 A7 ^_B7_______ 五、發明說明（Μ)The title compound was obtained as a solid (0.48 g, 26%). NMR (DMS0-d6): δ 8.21 (d, J = 9 Hz, 1H), 7.65 (ddd, J = 2, 6, 8 Hz, iH), 7.57-7.40 (m, 2H), 7.30 (s, 1H), 7.23 (s, 2H), 2.56 (two overlapping quartets, J = 8 Hz, 2H), 2.43 (s, 3H), 2.37 (s, 3H), 1.56 (s, 3H), 1.13 (t, J = 8 Hz, 3H). Step 3 4-(9-m-2. 3 H g I-M if `` 2 · 3-b 1-m-4 ~ group) __ m The method in step 5 of Example 49 was followed by acetic acid 4-(9-bromo-2,3-dimethyl-naphthalene 骈 f 2,3 ~ b] -P. -4 -yl) -2 -Ethylbenzyl (1.5 g, 3.3 mmol), K0H solution (4.0 ml of a 1N solution, 4.0 mmol), tetrahydrofuran (55 ml), And methanol (37 ml) to obtain the marginal foam of the title compound (1.4 g, > 10fU): NMR (DMSOd6): δ 9.55 (s, 1H), 8.16 (d, J = 9 Hz, 1H), 7.62 (ddd, J = 1, 7, 8 Hz, 1H), 7.54 (d, J = 8 Hz, 1H), 7.44 (ddd, J = 1, 7, 8 Hz, 1H), 7.05-6.87 (m, 3H), 2.60 (complex m, ABX pattern, 2H), 2.41 (s, 3H), 1.59 (s, 3H), 1.13 (t, J = 8 Hz, 3H). 457- This paper size applies to China Home Standard (CNS) A4 Specification (210 x 297 mm) -------------------- Order --------- Line (Please read the back first (Please note this page before filling in this page) 510900 A7 ^ _B7 _______ V. Description of Invention (Μ)

步驟 4 ( 2 R ) - 2 _「4 職(9 齡漳-2 · 3 - 「Zj_lriLL -嗦朌-甚）- 7.某，茱氬基1二·1」1丙酸甲酯— 仿例4 9步驟6之方法，由4 - ( 9 -溴-2，3 -二甲基-葉駢【2,3-1)卜瞎吩-4-基）-2-乙酚（0.4 5克，1.16毫莫耳），（3) 羥基-3-苯丙酸甲酯（〇·31克，1·?2毫莫耳，三苯瞵（fl·45 克，1 · 7 2毫莫耳），偶氮二羧酸二乙酯（〇 · 2 7毫升，1 · 7 1毫莫耳）及無水苯（5毫升），於9 0 °C下反應1 8小時可製得標題化合物之玻狀物（G · 2 2克，3 3 % : NMR (DMSO-d6): δ 8.22 (d, J = 9 Hz, 1H), 7.66 (ddd, J = 3, 6, 8 Hz, 1H), 7.59-7.22 (m, 7H), 7.20-7.02 (m, 2H). 6.92 (dd. J = 2, 8 Uzt 111), 5.31 (m, 1H)，3.74 and 3.70 (two s,直生異構物，3H), 3.32 (m，2H), 2·64 (complexm, 2H), 2.45(s，3H)，1.55 (s, 3H), U2 and 1.10 (two t，J = 7 Hz,直生異構物，3H). 步驟 5 ( 2R ) -B案盼-4 -某）-2 - 某-茉氬基1二仿例4 9步驟7之方法，由（2 R ) - 2 - [ 4 - ( 9 -溴-2， 3 -二甲Step 4 (2 R)-2 _ "4 positions (9-year Zhang-2-3-" Zj_lriLL-甚-even)-7. Some, ruthenium 1 2 · 1 "1 methyl propionate-example 4 9 The method of step 6 consists of 4-(9 -bromo-2,3-dimethyl-phyllo [2,3-1) buphenphen-4-yl) -2-ethylphenol (0.4 5 g, 1.16 millimoles), (3) hydroxy-3-phenylpropionic acid methyl ester (0.31 grams, 1.2 millimoles, triphenylhydrazone (fl.45 grams, 1.72 millimoles), Diethyl azodicarboxylate (0.27 ml, 1.71 mmol) and anhydrous benzene (5 ml) were reacted at 90 ° C for 18 hours to obtain a glassy substance of the title compound. (G · 22 g, 33%: NMR (DMSO-d6): δ 8.22 (d, J = 9 Hz, 1H), 7.66 (ddd, J = 3, 6, 8 Hz, 1H), 7.59-7.22 (m, 7H), 7.20-7.02 (m, 2H). 6.92 (dd. J = 2, 8 Uzt 111), 5.31 (m, 1H), 3.74 and 3.70 (two s, orthoisomers, 3H) , 3.32 (m, 2H), 2.64 (complexm, 2H), 2.45 (s, 3H), 1.55 (s, 3H), U2 and 1.10 (two t, J = 7 Hz, orthoisomer, 3H ). Step 5 (2R) -B case Pan-4 -some) -2-some-jaw arginyl 1 two simulation example 4 9 The method of step 7, from (2 R)-2-[4-(9 -Br -twenty three - Second

基-萘駢[2, 3-b卜時盼-4-基）-2-乙基-苯氧基卜卜苯丙酸甲酯（0*22克，（1.38毫莫耳），K0H溶液（〇·46毫升之1N溶液，0.46毫莫耳），四氫呋喃（15毫升），及甲醇（5毫升）可製得標題化合物白色固體（〇 . 1 9克，9 0 % ) 〇 P t · R 〇 U [ a ] 2 5 / D = +1.55° (8.396 mg/mL,MeOH); NMR (DMSO-d6): 5 13.15(brs, 1H), 8.17 (dd, J =4, 9 Hz, 1H), 7.66-7.58 (m, 1H), 7.50-7.21 (m, 7H), 7.11-7.04 (m, 2H), 6.88 (dd, J = 4, 9 Hz，1H)，5·09 and 5.06 (two dd，J = 4, 8 Hz,直生異構物，1H)，3.24 (complex m，ABX pattern, 2H)，2·66 and 2·56 (四線之二重餐雙線， ABX pattern,直生異構物>2H)，2.42 and 2·40 (two s，直生異構物，3H)，1·53 and 1.52 (two s，直生異構物，3Η)，1.08 and 1.06 (two t，J = 8 Ηζ，直生異構物， 3H); MS(EI): [M+], 1 溴同位素式樣，558/560; Anal. Gale, for C31H27Br03S: C，66.54, Η, 4·86,Ν，0.00· Found: C，66.91，Η，5·28，Ν，-0·07· -1 58- 本紙張尺度適用中國國家標準（CNS)A4規格（210 x 297公釐） (請先閱讀背面之注意事項再填寫本頁) i 訂---------線· 經濟部智慧財產局員工消費合作社印製 510900 經濟部智慧財產局員工消費合作社印製 A7 B7 五、發明說明（⑺）例78 2 -海- 4 - ( 2 , 3 -二申某-赛駢「2 > 3 - b Ί -眹 P南- 4 -某）- 6 - 乙1 仿例49步驟1之方法，由3-溴-5-乙基-對-大舖香醇酸 (4.95克，：19<1毫莫耳），草_氯（1.8毫升，20.6毫莫耳），N，N -二甲基甲醯胺（2滴），2， 3 -二甲基-5 - 苄呋喃（4 · 3克，2 3 · 1毫莫耳），氯化錫（I V ) ( 2 · 5毫升，21· 4毫莫耳），及無水二氯甲烷（72毫升）及可製得油（7 · 8 5克），其可不經純化而使用。仿例4 9步驟2之方法，由（2 -苄基-4，5 -二甲呋喃-3-基）-(3 -溴-5 -乙基-4 -甲氯苯基）-甲顚| ( 7 · 8 5克， 1 8 · 4毫莫耳），三溴化硼（】.3 · 2毫升，1 4 · 0毫莫耳），及二氯甲烷（6 3毫升），於5 0 °C下反應2小時可製得標題化合物之白色固體（〇_85克，12%): (DMSO-d6): δ 9.17 (s, 1H), 7.99 (d, J = 8 Hz, 1H), 7.95 (s, 1H), 7.52 (d, J = 8Hz, 1H), 7.42 (ddd, J = 1, 7, 8 Hz, 1H), 7.37-7.30 (m, 2H), 7.10 (d, J = 2 Hz, 1H), 2.80-2.60 (complex m, ABX pattern, 2H), 2.37 (s, 3H), 1.59 (s, 3H), 1.15 (t, J = 8 Hz，3H); MS〇EI): [M+]，1 溴同位素式樣，394/3%; Anal· Calc, for C22H19Br02: C, 66.85, H, 4.84, N, 0.00. Found: C, 67.07, H, 4.85, N, 0.05. 例79 (R ) -2 -「2-淳-(2*__3-二甲某-養 Etf Γ 2 . 3 - bl-映喃-4~~ 某）- π某-茱氩甚1 - 3-茉丙酴步驟 1 ( 2 R ) - 2 -「2 -淳 _ 4 - ( 2 * 3 - 二甲某-養駢 f 2 · 3 - h 1 -映喃-4 -基）-6 -乙某-茱氩某1 - 3 -茱丙酴申酯彷例4 9步驟6之方法，由2 -溴-4 - ( 2，3 -二甲基-萘駢 -1 59- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) --------訂---------· 510900 A7 B7 五、發明說明（αί) [2，3-b卜呋喃-4-基）-6-乙酚（0·3克，0.76毫莫耳），（S ) - 2 -羥基-3 -苯丙酸甲酯（〇 · 5 4克，3 · 0毫莫耳） (請先閱讀背面之注意事項再填寫本頁) ，三苯瞵（0.80克，3·1毫莫耳），偶氮二羧酸二乙酷 (〇·48毫升，3.0毫莫耳）及無水苯（1·〇毫升），於 10fl°C下反應12小時可製得檫題化合物之固體（D · 37克， 88%): NMR (DMSO-d6): δ 8·02 (d，J = 8 Hz, 1H)，7·99 (s，1H)，7.54-7.22 (m， 10H)，5.08 and 5.02 (two dd，J = 6, 8 Hz，直生異構物，3H)，3.60 and 3·57 (two s，直生異構物，3H)，3·47-3·30 (m，2H)，2.80-2.52 (complex m，ABX pattern,直生異構物，2H)，2·40 and 2·39 (two s，直生異構物，3H)，1·58 and 1·53 (two s，直生異構物,3H)，1·12 and 1·10 (two t，J = 8 Hz，直生異構物,3H); MS(EI): [M + ]，〗溴同位素式樣，5 5 6 / 5 5 8。步驟 2 ( 2 R )嫌 2 -「一漳-4 - ( 2 · 一二 _里一基一一―養駢 12 ·. J.·二bl -眹醸-4-某> 某-茱氯基丄仿例4 9步驟7之方法，由（2 R ) - 2 - [ 2 -溴-4 - ( 2，3 -二甲基 -葉駢[253-b卜呋喃-4-基卜6-乙基-苯氣基】-3-苯丙酸甲酯（G.34克，Q.61毫莫耳Κ0Η溶液（1·2毫升之1N溶液， 1.2毫莫耳），四氫呋喃（6.0毫升），及足量甲醇可製得含檫題化合物白色泡沫（〇· 31克，94%)之均質溶液：經濟部智慧財產局員工消費合作社印製 NMR (DMSO-d6): δ 8.bl (d, J = 8 Hz, 1H), 7.97 (d, J = 2 Hz, 1H), 7.48 (d, J = 9 Hz，2H)，7.46-7.22 (m, 9H), 7.20 (dd，J = 2, 6 Hz, 1H)，5.03 (m，1H)，3.35 (m， 2H), 2·94-2·55 (complex m，ABX pattern, 2H), 2.38 and 2·36 (two s，直生異構物， 3H)，1.56 and 1.51 (two s，直生異構物_ 3H)，1·11 and 1·10 (two t，J = 7 Hz，直生異構物，3H); MS(EI): [M+】，1溴同位素式樣，542/544; Anal. Calc, for C31H27Br04: C，68.51, H，5.01, N，0·00· Found: C，68.22, Η, 5.42, N，0.10. 例8 0 「2_溴 ( 2 , 3-二申甚-養駢—IH—T_rJ去喃-4 二基-1 _ 一 1 6 0 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印製 A7 ---___B7_____ 五、發明說明（W) 二Ir Z,某-茶氩某Ί - 丁酿步驟 1 4 -「2 -漳-4 - ( 2 · 3 -二 S 某-養駢丄2 _，—3 二上 Ir J夫醴.二Ir· 甚）-R - Γ,甚-莱氤某1 - 丁酸甲1 將2-溴-4- ( 2，3-二甲基-萘駢[2，3-b卜呋喃-4-基）一乙基酚（〇·30克，（K76毫莫耳），60%NaH(33毫克，〇·83毫莫耳），4 -溴丁酸甲酯（0.44毫升，3·82毫莫耳），及無水苯（]毫升）加熱至100°C6小時。加入4-溴丁酸甲酯（0 · 4 5毫升，3 · 9 1毫莫耳）及磺酸鉀（〇 · 5克， 3 . β 2毫莫耳）並加熱至1 〇〇 °C 6小時。層析以己烷/乙酸-Naphthylnaphthalene [2, 3-b buspan-4-yl) 2-ethyl-phenoxyb bupropionate methyl ester (0 * 22 g, (1.38 mmol), K0H solution ( 0.46 ml of a 1N solution, 0.46 mmol), tetrahydrofuran (15 ml), and methanol (5 ml) to give the title compound as a white solid (0.19 g, 90%). P t · R 〇 U [a] 2 5 / D = + 1.55 ° (8.396 mg / mL, MeOH); NMR (DMSO-d6): 5 13.15 (brs, 1H), 8.17 (dd, J = 4, 9 Hz, 1H), 7.66-7.58 (m, 1H), 7.50-7.21 (m, 7H), 7.11-7.04 (m, 2H), 6.88 (dd, J = 4, 9 Hz, 1H), 5.09 and 5.06 (two dd, J = 4, 8 Hz, orthoisomers, 1H), 3.24 (complex m, ABX pattern, 2H), 2.66 and 2.56 (double-line double meal, ABX pattern, orthomorphism Structure > 2H), 2.42 and 2.40 (two s, orthoisomer, 3H), 1.53 and 1.52 (two s, orthoisomer, 3Η), 1.08 and 1.06 (two t, J = 8 Ηζ, orthoisomer, 3H); MS (EI): [M +], 1 bromine isotope pattern, 558/560; Anal. Gale, for C31H27Br03S: C, 66.54, Η, 4.86, Ν ， 0.00 · Found: C ， 66.91 ， Η ， 5 · 28 ， N ， -0 · 07 · -1 58- Paper Standards apply to China National Standard (CNS) A4 specifications (210 x 297 mm) (Please read the precautions on the back before filling out this page) i Order --------- Line · Intellectual Property Bureau, Ministry of Economic Affairs, Employee Consumption Printed by the cooperative 510900 Printed by the Consumers ’Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Description of invention (⑺) Example 78 2 -Hai-4-(2, 3 -Second Shenmou-Sai 骈" 2 > 3-b Ί -眹 P South-4-a)-6-B 1 The method of step 49 of Example 49 was carried out from 3-bromo-5-ethyl-p-dapodol acid (4.95 g,: 19 < 1 mmol) , Grass_chlorine (1.8 ml, 20.6 mmol), N, N-dimethylformamide (2 drops), 2, 3 -dimethyl-5-benzylfuran (4 · 3 g, 2 3 · 1 millimolar), tin (IV) chloride (2.5 ml, 21.4 millimolar), and anhydrous dichloromethane (72 ml) and an oil (7.85 g) can be prepared. Purified and used. Example 4 9 Method of step 2 from (2-benzyl-4,5-dimethylfuran-3-yl)-(3-bromo-5 -ethyl-4 -methylchlorophenyl) -formamidine | (7.85 g, 18.4 mmol), boron tribromide (]. 3.2 ml, 14.0 mmol), and dichloromethane (63 ml) at 50 Reaction at ° C for 2 hours to obtain the title compound as a white solid (0-85 g, 12%): (DMSO-d6): δ 9.17 (s, 1H), 7.99 (d, J = 8 Hz, 1H), 7.95 (s, 1H), 7.52 (d, J = 8Hz, 1H), 7.42 (ddd, J = 1, 7, 8 Hz, 1H), 7.37-7.30 (m, 2H), 7.10 (d, J = 2 Hz, 1H), 2.80-2.60 (complex m, ABX pattern, 2H), 2.37 (s, 3H), 1.59 (s, 3H), 1.15 (t, J = 8 Hz, 3H); MS〇EI): [ M +], 1 bromine isotope pattern, 394/3%; Anal · Calc, for C22H19Br02: C, 66.85, H, 4.84, N, 0.00. Found: C, 67.07, H, 4.85, N, 0.05. Example 79 (R ) -2-"2-chun- (2 * __ 3-Dimethyl Mou-raising Etf Γ 2. 3-bl- Yingnan-4 ~~ Mou)-π Mou-Zhu Arxi 1-3- Mopromium Step 1 (2 R)-2-"2-Chun_ 4-(2 * 3-Dimethyl Mou-Yang F 2 · 3-h 1-Enan-4 -yl) -6-E Mou-Zhu Ar Mou 1-3-Chuproxil Ester Example 4 9 steps 6 method, from 2-bromo-4-(2,3-dimethyl-naphthalene-1) 59- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) (Please read the back first Please pay attention to this page before filling in this page) -------- Order --------- · 510900 A7 B7 V. Description of the Invention (αί) [2,3-b Bufuran-4-yl) -6-Ethylphenol (0.3 g, 0.76 mmol), (S)-2-Hydroxy-3 -phenylpropanoic acid methyl ester (0.54 g, 3.0 mmol) Note on the back page, fill in this page again), triphenylhydrazone (0.80 g, 3.1 mmol), diethyl azodicarboxylate (0.48 ml, 3.0 mmol) and anhydrous benzene (1 · 〇mL), reaction at 10fl ° C for 12 hours to obtain the title compound solid (D · 37 g, 88%): NMR (DMSO-d6): δ 8 · 02 (d, J = 8 Hz, 1H ), 7.99 (s, 1H), 7.54-7.22 (m, 10H), 5.08 and 5.02 (two dd, J = 6, 8 Hz, orthoisomer, 3H), 3.60 and 3.57 (two s, orthoisomer, 3H), 3.47-3.30 (m, 2H), 2.80-2.52 (complex m, ABX pattern, orthoisomer, 2H), 2.40 and 2.39 (two s, orthoisomer, 3H), 1.58 and 1 · 53 (two s, orthoisomer, 3H), 1 · 12 and 1 · 10 (two t, J = 8 Hz, orthoisomer, 3H); MS (EI): [M +] ,〗 Bromine isotope pattern, 5 5 6/5 5 8. Step 2 (2 R) Suspect 2-"Yi Zhang-4-(2 · One Two_Li One Base One One-Raise Twelve 12 ·. J. · Two bl-眹醸 -4-some > Someone-Chuchlo The method of the basic example 4 9 step 7 is based on (2 R)-2-[2 -bromo-4-(2,3 -dimethyl-phyllene [253-b Ethyl-phenylamino] -3-phenylpropanoic acid methyl ester (G.34 g, Q.61 millimolar K0Η solution (1.2 ml of a 1N solution, 1.2 mmol), tetrahydrofuran (6.0 ml), A homogeneous solution containing a white foam (0.31 g, 94%) containing the title compound can be prepared with sufficient methanol: NMR (DMSO-d6) printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs: δ 8.bl (d, J = 8 Hz, 1H), 7.97 (d, J = 2 Hz, 1H), 7.48 (d, J = 9 Hz, 2H), 7.46-7.22 (m, 9H), 7.20 (dd, J = 2, 6 Hz, 1H), 5.03 (m, 1H), 3.35 (m, 2H), 2.94-2 · 55 (complex m, ABX pattern, 2H), 2.38 and 2.36 (two s, orthoisomers , 3H), 1.56 and 1.51 (two s, orthoisomer_ 3H), 1.11 and 1 · 10 (two t, J = 7 Hz, orthoisomer, 3H); MS (EI): [M +], 1 bromine isotope pattern, 542/544; Anal. Calc, for C31H27Br04: C, 68.51, H 5.01, N, 0 · 00 · Found: C, 68.22, 5., 5.42, N, 0.10. Example 8 0 "2_Bromo (2, 3-Di-Shen-Yan-IH-T_rJ-Dan-4 diyl -1 _ 1 1 6 0-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 ---___ B7_____ V. Description of Invention (W) 2 Ir Z, a certain-tea argon a certain 丁-Ding brewing step 1 4-"2-Zhang-4-(2 · 3-two S a-raising 骈丄 2 _,-3 two on Ir J husband 醴. Two Ir · Even) -R-Γ, even-Lyme 1-butyric acid methyl 1 -bromo-4- (2,3-dimethyl-naphthalene [2,3-b bufuran-4-yl) a Ethyl phenol (0.30 g, (K76 mmol), 60% NaH (33 mg, 0.83 mmol), methyl 4-bromobutyrate (0.44 ml, 3.82 mmol), And anhydrous benzene (] ml) was heated to 100 ° C for 6 hours. Add methyl 4-bromobutyrate (0.45 ml, 3.91 mmol) and potassium sulfonate (0.5 g, 3. β 2 mmol) and heat to 1000 ° C 6 hour. Hexane / acetic acid

乙酯可製得檫題化合物之固體（〇 · Η克，8 U) : N MR (DMSO-d6): δ 8.00 (d，J = 8 Hz，1H)，7.98 (s, 1H)，7.48 (d, J = 8 Hz，1H)，7·46 (d， J = 2 Hz，1H)，7.43 (ddd，J = 1，7, 8 Hz, 1H)，7.35 (ddd，J = 1，7, 8 Hz，1H)，7·26 (d, J = 2 Hz, 1H), 4.03 (dd, J = 6, 9 Hz, 1H), 3.98 (dd, J = 6, 9 Hz, 1H), 3.63 (s, 3H), 2.74 (d of quartets, J = 7, 15 Hz, 1H), 2.69 (d of quartets, J = 7, 15 Hz, 1H), 2.62 (t, J = 7 Hz, 2H), 2.38 (s, 3H), 2.09 (quintet, J = 7 Hz, 2H), 1.56 (s, 3H), 1.18 (t.，J d H z，3 H ) ; M S ( E I ) : [ M + ]，1 溴同位素式樣，4 9 4 / 4 9 6。步驟 2 4 _ r m 4 - ( 2 · 3-二一m:m:_ 華）-6 -乙基-篆氫某1二丁酸一彷例4 9步驟？之方法，由4 - [ 2 -溴-4 - ( 2，3 -二甲基-蔡駢 [2，3-b] -呋喃-4-基0-6 -乙基-苯氧基卜丁酸甲酯（〇·31克，0 β 6 3毫莫耳），K 0 Η溶液（1 · 2 5毫升之1 N溶液，1 · 2 5毫莫耳），四氫呋喃（6 · 3毫升），及足量甲_可製得含標題化合物白色泡沫（〇 β 2 6克，8 7 % )之均質溶液：Ν Μ β 本紙張尺度適用中國國家標準（CNS)A4規格（210 χ 297公釐) --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 510900 經濟部智慧財產局員工消費合作社印製 Α7 Β7 五、發明說明（、k) (DMS0-d6): δ 12.15Xbr s, 1H), 8.01 (d, J = 8 Hz, 1H), 7.98 (s, 1H), 7.48 (d, J = 8Ethyl ester can be used to prepare the title compound as a solid (0.08 g, 8 U): N MR (DMSO-d6): δ 8.00 (d, J = 8 Hz, 1H), 7.98 (s, 1H), 7.48 ( d, J = 8 Hz, 1H), 7.46 (d, J = 2 Hz, 1H), 7.43 (ddd, J = 1, 7, 8 Hz, 1H), 7.35 (ddd, J = 1, 7 ,, 8 Hz, 1H), 7.26 (d, J = 2 Hz, 1H), 4.03 (dd, J = 6, 9 Hz, 1H), 3.98 (dd, J = 6, 9 Hz, 1H), 3.63 ( s, 3H), 2.74 (d of quartets, J = 7, 15 Hz, 1H), 2.69 (d of quartets, J = 7, 15 Hz, 1H), 2.62 (t, J = 7 Hz, 2H), 2.38 (s, 3H), 2.09 (quintet, J = 7 Hz, 2H), 1.56 (s, 3H), 1.18 (t., J d H z, 3 H); MS (EI): [M +], 1 Bromine isotope pattern, 4 9 4/4 9 6. Step 2 4 _ r m 4-(2 · 3-Di 1 m: m: _ Hua) -6 -ethyl-fluorine 1 dibutyric acid 1 Example 4 9 steps? The method consists of 4-[2 -bromo-4-(2,3-dimethyl-Ceamidine [2,3-b] -furan-4-yl 0-6 -ethyl-phenoxybutyric acid Methyl ester (0.31 g, 0 β 6 3 mmol), K 0 Η solution (1.25 ml of a 1 N solution, 1.2 mg), tetrahydrofuran (6.3 ml), and A sufficient amount of A_ can prepare a homogeneous solution containing the title compound as a white foam (〇β26g, 87%): NM β This paper size applies the Chinese National Standard (CNS) A4 specification (210 χ 297 mm)- ------------------- Order --------- Line (Please read the notes on the back before filling this page) 510900 Employees of the Intellectual Property Bureau of the Ministry of Economic Affairs Printed by the consumer cooperative A7 Β7 V. Description of the invention (, k) (DMS0-d6): δ 12.15Xbr s, 1H), 8.01 (d, J = 8 Hz, 1H), 7.98 (s, 1H), 7.48 (d , J = 8

Hz, 1H), 7.46 (d, J = 2 Hz, 1H), 7.42 (ddd, J = 1, 7, 8 Hz, 1H), 7.35 (ddd, J = 1, 7, 8 Hz, 1H), 7.26 (d, J = 2 Hz, 1H), 4.04 (dd, J = 6, 9 Hz, 1H), 3.98 (dd, J = 6, 9 Hz, 1H), 2.74 (d of quartets, J = 7, 15 Hz, 1H), 2.71 (d of quartets, J = 7, 15 Hz, 1H), 2.53 (t, J = 7 Hz, 2H)，2·38 (s，3H), 2·06 (quintet, J = 7 Hz, 2H)，1.56 (s，3H)，1.19 (t，J = 7 Hz，3H); MS(-ESI): [M-H]，l 溴同位素式樣，479/481; Anal. Calc, for C26H25Br04: C, 64.87, H，5·23, N，0·00· Found: C，64·94, H，5.34, N，0.08. 例8 1 4-C2-溴-4-（2. 3 - 二甲某-養酣「2· 3-bl -呋喃 γΙγ.基」I__ -fi-7，某-荣氬某1-丁醱胺0.4水合物將4-[2-溴-4-(2，3-二甲基-萘駢丨2，3-1)]-呋喃-4-基）-6-乙基-苯氣基卜丁酸（60毫克，0·12毫莫耳），草_ 氯（1 0 · 8 U 1，0 · 1 2毫莫耳），Ν，Ν _二甲基甲醯胺（2 · 0 # 1 )，及二氯甲烷（1 . 〇毫升）於室溫下攪拌。2 · 5小時後加入含氨之乙腈（5毫升）飽和溶液，於室溫下攪拌2天。減壓濃縮，懸浮於3 %乙醇之水（3 1毫升），於室溫下攪拌1 8 小時。過濾，水洗並風乾可製得標題化合物之樣白色固體（5 2 · 6 毫克，8 8 % ) ·· NMR (DMSO-d6): δ 8.00 (d，J = 8 Ηζ，1Η)，7·98 (s， 1Η)，7.49 (d，J = 8 Hz, 1Η), 7.45 (d, J = 2 Ηζ，1Η)，7.43 (ddd，J = 1，7, 8 Ηζ，1Η)， 7.35 (ddd overlapping with a br s, J = 1, 7, 8 Hz, 2H), 7.25 (d, J = 2 Hz, 1H), 6.79 (br s, 1H), 4Ό1 (dd, J = 6, 9 Hz, 1H), 3.96 (dd, J = 6, 9 Hz, 1H), 2.75 (d of quartets, J = 7, 15 Hz, 1H), 2.71 (d of quartets, J = 7, 15 Hz, 1H), 2.38 (s, 3H), 2.35 (t, J = 7 Hz, 2H), 2.04 (quintet, J = 7 Hz, 2H), 1.56 (s, 3H), 1.19 (M = 7 Hz, 3H); MS(+ESI): [M+H]+, 1 溴同位素式樣，480/482; Anal. Calc, for C26H26BrNO3¥0.4H2O: C, 64.04, H, 5.54, N, 2.87. Found: C, 64.01, H, 5.43, N, 2.89. 例82 4 - ( 2 · 3 -二 g 某-赛 _「2· 3 - h 1 -眹瞒-4 -基 j„: 6 二乙-Α- -162- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7_ 五、發明說明（) 步驟1 (2 -苄某-4· 5 -二申眹P南-3-某）-申氳某-3- 仿例49步驟1之方法，由3-乙基-對-大顔香醇酸（5.0 克，2 7 s ?毫莫耳），草醯氯（2 J毫升，3 1 · 0毫莫耳），N， N -二甲基甲醯胺（2滴），2， 3 -二甲基-5 -苄呋喃（6 · 2克， 3 3 . 3毫莫耳），氯化錫（I V ) ( 3 β 6毫升，3 0 . 8毫莫耳），及無水二氯甲烷（1 7 7毫升）及可製得標題化合物之油Hz, 1H), 7.46 (d, J = 2 Hz, 1H), 7.42 (ddd, J = 1, 7, 8 Hz, 1H), 7.35 (ddd, J = 1, 7, 8 Hz, 1H), 7.26 (d, J = 2 Hz, 1H), 4.04 (dd, J = 6, 9 Hz, 1H), 3.98 (dd, J = 6, 9 Hz, 1H), 2.74 (d of quartets, J = 7, 15 Hz, 1H), 2.71 (d of quartets, J = 7, 15 Hz, 1H), 2.53 (t, J = 7 Hz, 2H), 2.38 (s, 3H), 2.06 (quintet, J = 7 Hz, 2H), 1.56 (s, 3H), 1.19 (t, J = 7 Hz, 3H); MS (-ESI): [MH], l bromine isotope pattern, 479/481; Anal. Calc, for C26H25Br04 : C, 64.87, H, 5.23, N, 0.00. Found: C, 64.94, H, 5.34, N, 0.08. Example 8 1 4-C2-Bromo-4- (2.3.-2 Memou-Nanyang "2.3-bl-furan γ Ιγ. Group" I __- fi-7, m-rong argon 1-butanidine 0.4 hydrate will be 4- [2-bromo-4- (2,3 -Dimethyl-naphthalene 骈 2,3-1)]-furan-4-yl) -6-ethyl-benzylphenylbutyric acid (60 mg, 0.12 mmol), grass_chlorine ( 1 0 · 8 U 1,0 · 12 mmol), N, N-dimethylformamide (2. 0 # 1), and dichloromethane (1.0 ml) were stirred at room temperature. After 2.5 hours, a saturated solution of ammonia in acetonitrile (5 ml) was added and the mixture was stirred at room temperature for 2 days. It was concentrated under reduced pressure, suspended in 3% ethanol water (31 ml), and stirred at room temperature for 18 hours. Filtration, washing with water and air-drying yielded the title compound as a white solid (52. 6 mg, 88%). NMR (DMSO-d6): δ 8.00 (d, J = 8 Ηζ, 1Η), 7.98 (s, 1Η), 7.49 (d, J = 8 Hz, 1Η), 7.45 (d, J = 2 Ηζ, 1Η), 7.43 (ddd, J = 1, 7, 8 Ηζ, 1Η), 7.35 (ddd overlapping with a br s, J = 1, 7, 8 Hz, 2H), 7.25 (d, J = 2 Hz, 1H), 6.79 (br s, 1H), 4Ό1 (dd, J = 6, 9 Hz, 1H) , 3.96 (dd, J = 6, 9 Hz, 1H), 2.75 (d of quartets, J = 7, 15 Hz, 1H), 2.71 (d of quartets, J = 7, 15 Hz, 1H), 2.38 (s , 3H), 2.35 (t, J = 7 Hz, 2H), 2.04 (quintet, J = 7 Hz, 2H), 1.56 (s, 3H), 1.19 (M = 7 Hz, 3H); MS (+ ESI) : [M + H] +, 1 Bromine isotope pattern, 480/482; Anal. Calc, for C26H26BrNO3 ¥ 0.4H2O: C, 64.04, H, 5.54, N, 2.87. Found: C, 64.01, H, 5.43, N , 2.89. Example 82 4-(2 · 3-2 g a-race _ "2 · 3-h 1-concealed-4-base j„: 6 diethyl-Α--162- This paper size applies to China Standard (CNS) A4 specification (210 X 297 mm) -------------------- Order --------- line (Please read the Matters needing attention ) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7_ V. Description of the invention () Step 1 (2-benzyl-4-5-two-shen 眹 P south -3--)-Shen 氲 -3- imitation Example 49: The method of step 1 consists of 3-ethyl-p-swelling alkyd acid (5.0 g, 27 s? Millimolar), chloramphenicol (2 J ml, 3 1.0 millimoles), N , N-dimethylformamide (2 drops), 2, 3 -dimethyl-5-benzylfuran (6.2 g, 3 3.3 mmol), tin (IV) chloride (3 β 6 ml, 30.8 mmol), and anhydrous dichloromethane (177 ml) and an oil to give the title compound

(7.24 克，7 5%) : (DMS0-cl6):<y 7.61(dd,J = 2.8Hz,lH 7.54 (d, J = 2 Hz, 1H), 7.28-7.13 (m, 3H), 7.09-7.03 (m, 3H), 3.86 (s, 3H), 3.82 (s, 2H), 2.55 (q, J = 7 Hz, 2H), 2.16 (s, 3H), 1.78 (s, 3H), 1.08 (t, J = 7 Hz, 3H). 步驟2 4 - ( 2 > 3-二申某-棻酣f2· 3-bl-眹喃-4-某）-2- 彷例4 9步驟2之方法，由（2 -苄基-4，5 -二甲呋喃 -3 -基）-(4 -甲氣苯基-3 -乙苯基）-甲酮（7 · 0克， 2(Κί毫莫耳），三溴化硼（14.4毫升，152.3毫莫耳），及二氯甲烷（6 9毫升），可製得標題化合物之戀白色固讎（0 · 6 1 克，9 · 6 % ) : ( D M S 0 - d 6 ) : β 9 · 4 5 ( s， 1Η), 7.97 (d, J = 8 Hz, 1H), 7.90 (s, 1H), 7.55 (d, J = 8 Hz, 1H), 7.39 (ddd, J = 1, 7, 8 Hz, 1H), 7.29 (ddd, J = 1, 7, 8 Hz, 1H), 7.02 (d, J = 2 Hz, 1H), 6.98 (dd, J = 2, 8 Hz, 1H), 6.91 (d, J = 8 Hz, 1H), 2.63 (d of quartets, J = 7, 14 Hz, 1H), 2.58 (d of quartets, J = 7, 14 Hz, 1H), 2.36 (s, 3H), 1.56 (s, 3H), 1.14 (t, J = 7 Hz, 3H); MS(EI): [M+]316. 例83 (R) - 2 - U -（ 9 -淳- 2 , 3 -二甲某-赛駢 f 2 * 3 - h 睐盼-4- 甚）-2 -丙某茱氫某]Ί茱丙酴步驟1 ( 2 -节某-4 · 「)-二申睐盼- 3 '某）--申氣某Ί -163- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 510900 A7 B7_ 五、發明說明丙某茱某1 -申_ 仿例49步驟1之方法，由3-丙基-對-大歸香醇酸（3.0 (請先閱讀背面之注意事項再填寫本頁) 克，15。4毫莫耳），草醯氯（1·48毫升，17·0毫莫耳），Ν， Ν -二甲基甲醯胺（2滴> ，2， 3 -二甲基-5 -苄睹盼 (3 . 7 5克，]8 · 5毫莫耳），氯化錫（I V ) ( 1 · 9 9毫升， 1 7 . 0毫莫耳），及無水二氯甲烷（9 9毫升）及可製得標題化合物之油（2 « 1 1 克，3 8 % ) : ( D M S 0 - d 6 ) : 7 · 5 8 ( d d， J = 2, 8 Hz，1H)，7·53 (d，J = 2 Hz，1H)，7.25-7.11 (m，3H)，7·10-7·03 (m，3H)， 3.86 (s, 3H), 3.84 (s, 2H), 2.54 (t, J = 7 Hz, 2H), 2.26 (s, 3H), 1.81 (s, 3H), 1.51 (sextet, J = 7 Hz, 2H), 0.87 (t, J = 7 Hz, 3H); MS(EI): [M+] 378. 步驟 2 4-(2. 3 - 二某-藜駢 f 2 · 3 - h ] - gt 盼、4 _ 某）- 2 - 丙酚仿例4 9步驟2之方法，由（2 -芣基-4 , 5 -二甲瞎吩 - 3 -基）-(4 -甲氧苯基-3 -丙苯基）-甲酮（2 · 7 0克， 7 ·1毫莫耳），三溴化硼（5. 12毫升，54· 2毫莫耳），及二氯甲烷（2 4 . 5毫升），可製得標題化合物之固體 (ί · 7 7 克，7 1%) : (DMS0-d6):5 9.44(s,lH), 8.42 (s, 1H), 7.93 (d, J = 8 Hz, 1H), 7.50-7.25 (m, 3H), 7.05-6.88 (m, 3H), 2.61 (m, 1H)，2·52 (m，1H)，2.39 (s，3H), 1.70-1.50 (m 含一單線在 δ 1.63, 5H), 0.88 (t, J = 7 Hz, 3H); MS(EI): [M+] 346. 步驟3 乙酸4 - ( 2 , 3 -二甲某-赛駢F 2 , 3 - b 1 - B家盼- 4 -某）經濟部智慧財產局員工消費合作社印製 - 2 -丙某茉酯仿例4 9步驟3之方法，由4 - ( 2，3 -二甲基-萘駢[2， 3 - b ] - 瞎吩-4-基）-2-丙酚（1.3克，3·8毫莫耳），乙酑（0·46 毫升，4.9毫莫耳），及吡啶（7 ·5毫升）可製得産物，層析以己烷/乙酸乙酯可製得標題化合物之固體（0 . 8 1 -164- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印製 510900 A7 B7 五、發明說明克，5 0%) : NMR (DMSO-d6): δ 8.50 (s, 1H), 7.98 (d, J = 9 Hz, 1H), 7.51-7.44 (m, 1H), 7.40-7.36 (m, 2H), 7.26 (s, 1H), 7.23 (s, 2H), 2.55 (m, 2H), 2.42 (s, 3H), 2.38 (s，3H)，1.64-1.53 (m 含一雙線在 δ 1.61，5H), 0·88 (t, J = 7 Hz，3H); MS(EI): [M+]388. 步驟4乙酴4 _ ( 9 -淳-2 . 2 -二田甚-養駢f 2 · 3 - h Ί -睐盼 -4 -某）-2 -丙甚茱酯仿例49步驟4之方法，由乙酸4- ( 2, 3-二甲基-萘駢[2，3-h卜瞎吩-4-基）-2-丙基-苯_ (〇.80克， 2」毫莫耳），氯化鐵（16·7毫克，〇·1毫莫耳），溴（0.1 2毫升，2.3毫莫耳）及二氯甲烷（21毫升）(7.24 g, 7 5%): (DMS0-cl6): < y 7.61 (dd, J = 2.8Hz, lH 7.54 (d, J = 2 Hz, 1H), 7.28-7.13 (m, 3H), 7.09 -7.03 (m, 3H), 3.86 (s, 3H), 3.82 (s, 2H), 2.55 (q, J = 7 Hz, 2H), 2.16 (s, 3H), 1.78 (s, 3H), 1.08 ( t, J = 7 Hz, 3H). Step 2 4-(2 > 3- 二申某-棻酣 f2 · 3-bl- 眹 RAN-4-some) -2- Example 4 9 Step 2 By (2-benzyl-4,5-dimethylfuran-3 -yl)-(4-methylaminophenyl-3 -ethylphenyl) -methanone (7.0 g, 2 (Κίmmol) ), Boron tribromide (14.4 ml, 152.3 millimoles), and dichloromethane (69 ml), the title compound of white solid tincture (0.61 g, 9.6%) was prepared: ( DMS 0-d 6): β 9 · 4 5 (s, 1Η), 7.97 (d, J = 8 Hz, 1H), 7.90 (s, 1H), 7.55 (d, J = 8 Hz, 1H), 7.39 (ddd, J = 1, 7, 8 Hz, 1H), 7.29 (ddd, J = 1, 7, 8 Hz, 1H), 7.02 (d, J = 2 Hz, 1H), 6.98 (dd, J = 2 , 8 Hz, 1H), 6.91 (d, J = 8 Hz, 1H), 2.63 (d of quartets, J = 7, 14 Hz, 1H), 2.58 (d of quartets, J = 7, 14 Hz, 1H) , 2.36 (s, 3H), 1.56 (s, 3H), 1.14 (t, J = 7 Hz, 3H); MS (EI): [M +] 316. Example 83 (R)-2-U-(9-Chun-2, 3-Dijia Mou-Sai Ye f 2 * 3-h Phan -4- even)-2-Bing Mo Zhu Hou]] Fructus Carbo 1 (2 -Jiemou-4 · ") -Second application favor-3 'something'-Shenqi a certain job -163- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm)- ------------------- Order --------- Line (Please read the precautions on the back before filling this page) 510900 A7 B7_ V. Description of the invention Bingmou Zhumou 1-Shen_ The method of step 1 of Example 49 is based on 3-propyl-p-greatine alkyd acid (3.0 (please read the notes on the back before filling this page) grams, 15.4 mmol Ear), chloramphenicol (1.48 ml, 17.0 mmol), Ν, Ν-dimethylformamide (2 drops), 2, 3 -dimethyl-5-benzylamine ( 3.5 grams, 8.5 millimoles), tin (IV) chloride (1.99 milliliters, 17.0 millimoles), and anhydrous dichloromethane (99 milliliters) and can be prepared Oil of the title compound (2 «1 1 g, 3 8%): (DMS 0-d 6): 7 · 5 8 (dd, J = 2, 8 Hz, 1H), 7.53 (d, J = 2 Hz, 1H), 7.25-7.11 (m, 3H), 7.10-7 · 03 (m, 3H), 3.86 (s, 3H) , 3.84 (s, 2H), 2.54 (t, J = 7 Hz, 2H), 2.26 (s, 3H), 1.81 (s, 3H), 1.51 (sextet, J = 7 Hz, 2H), 0.87 (t, J = 7 Hz, 3H); MS (EI): [M +] 378. Step 2 4- (2. 3-Ermou-quinoa f 2 · 3-h]-gt Pan, 4 _ mr)-2- Propofol Example 4 The method of step 2 of 9 was prepared from (2-fluorenyl-4,5-dimethylbenzophen-3-yl)-(4-methoxyphenyl-3 -propylphenyl) -methanone ( 2.70 g, 7.1 mmoles), boron tribromide (5.12 ml, 54.2 mmoles), and dichloromethane (24. 5 ml) to prepare the title compound Solid (til · 7 g, 7 1%): (DMS0-d6): 5 9.44 (s, lH), 8.42 (s, 1H), 7.93 (d, J = 8 Hz, 1H), 7.50-7.25 ( m, 3H), 7.05-6.88 (m, 3H), 2.61 (m, 1H), 2.52 (m, 1H), 2.39 (s, 3H), 1.70-1.50 (m with a single line at δ 1.63, 5H ), 0.88 (t, J = 7 Hz, 3H); MS (EI): [M +] 346. Step 3 Acetic acid 4-(2, 3-dimethyl a-Saiyan F 2, 3-b 1-B Hope-4-A) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs-2-Propyl jasmonate Example 4 9 The method of step 3, from 4-(2, 3-dimethyl-naphthalene [2, 3 -b]-benzophen-4-yl) -2-propene (1.3 g, 3.8 mmol), acetamidine (0.46 ml, 4.9 mmol), and pyridine (7.5 ml) were prepared by chromatography. The title compound was obtained as a solid (0.8 1 -164- This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm)) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7 , 50%): NMR (DMSO-d6): δ 8.50 (s, 1H), 7.98 (d, J = 9 Hz, 1H), 7.51-7.44 (m, 1H), 7.40-7.36 (m, 2H) , 7.26 (s, 1H), 7.23 (s, 2H), 2.55 (m, 2H), 2.42 (s, 3H), 2.38 (s, 3H), 1.64-1.53 (m with a double line at δ 1.61, 5H ), 0 · 88 (t, J = 7 Hz, 3H); MS (EI): [M +] 388. Step 4 酴酴 4 _ (9---2. 2-二田田-养骈 f 2 · 3-h Ί -Lanpan-4 -a)-2-propacol ester 49 method of step 4 from 4- (2, 3-dimethyl-naphthalene acetic acid [2, 3-h Phen-4-yl) -2-propyl-benzene- (0.80 g, 2 "mmol), ferric chloride (16.7 mg, 0.1 mmol), bromine (0.1 2 ml, 2.3 mmol) and dichloromethane (21 ml)

可製得標題化合物之固體（0 . 38克，39¾) : NMRThe title compound was obtained as a solid (0.38 g, 39¾): NMR

(DMSO-d6): δ 8.20 (d, J = 9 Hz, 1H), 7.65 (ddd, J = 1, 6, 8 Hz, 1H), 7.48 (ddd, J = 1, 6, 8 Hz, 1H), 7.43 (d, J = 8 Hz, 1H), 7.28 (s, 1H), 7.23 (s, 2H), 2.53 (m, 2H), 2.43 (s,3H)，2.36 (s,3H)，1.63-1.50 (m 含一雙線在 δ 1.57, 5H)，0.86 (t，J 二 7 H z，3 H ) ; M S ( E I ) : [ M + 】，1 溴同位素式樣，4 6 6 / 4 6 8。步驟 5 ( 2 R ) - 2 - Γ 4 - ( 9 -淳-2 . 3ϋ_见盖二览」!LJL2-_t_.3- :!)」— -時盼-4 -某）-2 —丙某茱氛基二3二jim 仿例49步驟5之方法，由乙酸4- (9-溴-2， 3-二甲基- 禁駢[2, 3-b】-瞎盼-4-基）-2-丙基苯酯（〇·36克，0,77 毫莫耳），Κ0Η溶液（0.92毫升之1Ν溶液，0·92毫莫耳），四氫呋喃（1 1 . 4毫升），及甲醇（7 · 6毫升）可得4 -(9 -溴-2，3 -二甲基-萘駢[2，3 - b卜瞎盼-4 -基）-2 -丙酚（（K 6 2克）之固體（G β 6 2克），其可不經純化而使用。彷例49步驟β之方法，由4- (9-溴-2, 3-二甲基-萘駢 ί 2 , 3 - b卜睹吩-4 -基）_ 2 -丙酚（〇 · 7 ?毫莫耳），（S ) -1 6 5 - 本纸張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 1^^"" (請先閱讀背面之注意事項再填寫本頁) 510900 A7 _B7________ 五、發明說明水洗i次，於硫酸鈉下乾燥。減壓濃縮並層析以己烷/ 乙酸乙酯可製得標題化合物之黃色泡沫（〇·36克，27%)， (DMSO姻：δ 8.41 (s· 1Η), 8·21 (d, J * 9 Hz, 1Η), 7·68 (ddd, J * 2, 6, 8 Ha 1Η)， 7·57-7·45 (吼 2H># 7·05 (s, 2H)· 3·78 (s, 3H)· 2·30 (s, 6Η>· 2·08 (a· 3H)· 1·68 (»· 3H); MS(EI): ΙΜ+】，1 HI 冊位索式檨，482/484;>\||<|1£咖· for C25H23BrCMS: C· 62*11, Η* 4·80, N, 0·00. Found: C, 61·86, Η, 4·75, N, 0·04· 例85 乙酴 4-(9·溴 _(2· 3_ 二 W 甚-赛駢「2. 3-bl-Pf 盼-4 -某(DMSO-d6): δ 8.20 (d, J = 9 Hz, 1H), 7.65 (ddd, J = 1, 6, 8 Hz, 1H), 7.48 (ddd, J = 1, 6, 8 Hz, 1H) , 7.43 (d, J = 8 Hz, 1H), 7.28 (s, 1H), 7.23 (s, 2H), 2.53 (m, 2H), 2.43 (s, 3H), 2.36 (s, 3H), 1.63- 1.50 (m with a double line at δ 1.57, 5H), 0.86 (t, J 2 7 H z, 3 H); MS (EI): [M +], 1 bromine isotope pattern, 4 6 6/4 6 8 . Step 5 (2 R)-2-Γ 4-(9 -Chun-2 .3ϋ_See cover 2nd view "! LJL2-_t_.3-:!)" — -Shipan-4 -a) -2-C The method of step 5 of an example 49 in a certain sulfanyl group is from 4- (9-bromo-2,3-dimethyl-anhydro [2, 3-b] -blazepan-4-yl) acetate 2-propylphenyl ester (0.36 g, 0,77 mmol), K0Η solution (0.92 ml of 1N solution, 0.92 mmol), tetrahydrofuran (1.14 ml), and methanol (0.14 ml) (7 · 6 ml) to obtain 4- (9-bromo-2,3-dimethyl-naphthalenepyrene [2,3 -b bublamine-4 -yl) -2 -propanol ((K 6 2 g) The solid (G β 6 2 g), which can be used without purification. The method of step β of Example 49 is based on 4- (9-bromo-2, 3-dimethyl-naphthalene) 2, 3-b. See phen-4 -yl) _ 2-propofol (0.7? Millimolar), (S) -1 6 5-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) -------------------- Order --------- line 1 ^^ " " (Please read the notes on the back before filling this page ) 510900 A7 _B7________ V. Description of the invention Wash i times with water and dry under sodium sulfate. Concentrate under reduced pressure and chromatograph with hexane / ethyl acetate. Ethyl acid can be used to prepare the title compound as a yellow foam (0.36 g, 27%), (DMSO: δ 8.41 (s · 1Η), 8.21 (d, J * 9 Hz, 1Η), 7.68 (ddd, J * 2, 6, 8 Ha 1Η), 7.57-7 · 45 (Roar 2H ># 7.05 (s, 2H) · 3.78 (s, 3H) · 2.30 (s, 6Η > · 2 · 08 (a · 3H) · 1 · 68 (»· 3H); MS (EI): ΙΜ +], 1 HI booklet type 檨, 482/484; > \ || < | 1 £ Ca for C25H23BrCMS: 62 · 11, Η * 4.80, N, 0. 00. Found: C, 61 · 86, Η, 4.75, N, 0 · 04. Example 85 乙酴 4 -(9 · bromo_ (2 · 3_ 2W even-sai 骈「2. 3-bl-Pf hope-4 -a

I 酯茱甲 0 乙 1 驟步駢赛 - 某 & 二甚 (請先閱讀背面之注意事項再填寫本頁) 甲 I 2- 驟耳步莫 49毫例2 仿60 法方 _1|之茱由氯0 草二S毫香 1 鐘 6 6 大 1 5 對升基Ϊ 甲4· 克經濟部智慧財產局員工消費合作社印製 Ν, Ν -二甲基甲醯胺（2滴），2, 3-二甲基-5-苄基瞎吩 (14 · 6克，72 · 2毫莫耳），氮化錫（IV) (7·75毫升， 66·2毫莫耳），及無水二氯甲烷（ 3 0 0毫升）及油（24·4 克）製得，其可不經純化而使用。仿例4 9步驟2之方法，由（2 -芣基-4 , 5 -二甲瞎盼-3 - 基）-(4 -甲氣苯基）-甲顚1 (22.4克），三溴化硼 (17.1毫升，180.9毫莫耳），及二氯甲烷（120毫升）製得，殘渣以乙酐（7.4ffll，78.4mraol)，Bit聢58·1及二氯甲烷4 0 0 ml仿例49，步驟3處理，得固體9 · 83克，45.5%): NMR (DMSOd6): δ 8.48 (s, 1Η), 7.97 (d, J = 8 Hz, lH)f 7.50-7.33 (mt3H), 7.27 (s, iH), 121 (s, 2H)* 2.40 (s, 3H), 2.36 (sf 3H)t 2.19 (s, 3H), 1.58 ($, 3H); MS(+APC1): tM-PHJ 361. -1 8 7 - --------訂·--------· 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）經濟部智慧財產局員工消費合作社印制衣 510900 A7 __ B7 五、發明說明（从）步驟2 乙·盤二1二—mm -二甲基-赛駢「？. h 1 - gft 二·4二基.JL· 2 -二申某茱B§ 仿例4 9步驟4之方法，由乙酸4 - ( 2，3 -二甲基-萘駢 [233-b卜睹盼-4-基）-2 -甲基苯酯（5·0克^ 13·9毫莫耳），氯化鐵（0.11克，0.68毫莫耳），溴（14.3毫升於1.〇7柯四氯化确（15·3毫莫耳），及二氯甲烷（63毫升），可製得 (5 · 4 4 克，9 0 · 7 % )標題化合物：NMR (DMSO-d6): δ 8.20 (d，J = 9 Hz, 1Η)， 7.65 (ddd, J = 2, 6, 8 Hz, 1H), 7.52-7.42 (m, 2H), 7.30 (s, 1H), 7.23 (s, 2H), 2.43 (s, 3H), 2.36 (s, 3H), 2.20 (s, 3H). 1.56 (s，3H); MS(EI): [M+】，1 溴同位素式樣，438^: Anal· Calc· for C23H19B^2S: C, 62.87, Η, 4·36· Ν鎮 Faunck 例8 6 乙—酸二生二丄i二漠-2 -二胺甲某-3 -申某-棻駢「2 ▲ 3 - h 1 - Bt 盼—-4-基1 - 2 . β-二田某茱酯步驟1 乙酸一 4 - ( 9 - ?馨· 2 -溴申某-3 -申某-着_「2 , 3 - b 1 zM—盼-4-基1-2 > ft-二申某茱酯仿例4 9步驟4之方法，由乙酸4 - ( 2 -二乙胺甲基-3 -甲基-蔡駢[2，3-b] -瞎盼-4-基）-2，6 -二甲基苯酯（10.0 克，26·7毫莫耳），氯化鐵（0.23克，1.42毫莫耳），溴（1.51毫升於二氯甲烷（38毫升），29.4毫莫耳），及二氯甲烷（231毫升），可製得乙酸-4- ( 9-溴-2，3-二甲基-萘駢[2，3 - b卜睹吩-4 -基卜2，6 -二甲基苯酯 (6· G8克，55%)及標題化合物之黃色固體（1.60克）·♦ NMR (DMSO-d6): δ 8.28 (m, 1H), 7.62-7.56 (m, 2H), 7.41-7.37 (m, 1H), 7.06 (s, 2H), 4.70 (s, 2H), 2.42 (s, 3H), 2.24 (s, 6H), 1.72 (s, 3H); MS(EI): [M+], 2 溴同位素式樣，530/532/534; Anal· Calc, for C24H20Br2O2S: C，54.15, H, 3.79, N, 0.00. Found: C, 53；81, H, 3.61, N, 0.10. —168— 本紙張尺度適用中國國家標準（CNS)A4規格（210 x 297公釐） --------------------訂---------^ —^w— (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 510900 A7 B7 五、發明說明（步驟2 7,醱-4- ( Ώ-漳-2-二乙胺二甲基-蓋—駢— Γ 2 . 3 - b卜_盼-4 -某1 - 2 t 6二二甲某茱酯將乙酸- 4- (9-溴-2-溴甲基-3 -甲基-萘駢[2,3-b]-瞎盼 -4-基卜2，6-二甲基苯醋（1.21克，2·27毫莫耳）處理以二乙胺（〇·71毫升，6·82毫莫耳），磺酸鉀（0.94克，6·82毫莫耳）及Ν，Ν -二甲基甲醯胺（1 2 J毫升）。於室溫下1小時，倒入水（2 5 0毫升），過濾並水洗。風乾可製得標題化合物之黃色固體（lt13克，94·5¾):NMR(DMS0-(i6):3 8·19(d,lH), 7.66-7.61 (m, 1H), 7.47 (d, 2 Η), 7.13 (s, 2H), 3.73 (s, 2H), 2.58-2.52 (q, 4H), 2.40 (s, 3H), 2.16 (s, 6H), 1.61 (s，3H), 1.02 (t, 6H); MS(EI): [M+]，1 溴同位素式樣，523/525; Anal· Calc· for C28H30BrNO2S: C，64.12, H, 5.77, N, 2.67. Found: C, 63.30, H, 5.67, N, 2.55. 例87 2-「4-(9-漳-2-二乙胺申某-3_甲基-養駢『2*3-1>1-11家盼 - 4-某1-2· 6-二申茉氣甚-3_荣丙_ 步驟1 4 - ( 9 -漳-?-二^胺甲基'3 -甲某-赛 Γ 2 , 3 - h 1 - B寒盼- 4 -某1 - 2 · fi -二申酚仿例49步驟5之方法，由乙酸4 - (9-溴-2-二乙胺甲基- 3- 甲基-萘駢[2, 3-b卜B塞吩-4-基]-2, 6-二甲基苯酯（1.1 3克，2 · 15毫莫耳），Κ0Η溶液（2 6 58毫升之1N溶液，2 · 58毫莫耳），四氫呋喃（28毫升），及甲醇（19毫升）可得標題化合物之黃色固體（1·0克，9 6sl%):NMR(DMS0-d6):<y 8.47(s, 1H), 8.17 (d, 1H), 7.64-7.59 (m, 1H), 7.55-7.45 (m, 1H), 7.45-7.39 (m, 1H), 6.90 (s, 2H), 3.72 (s, 2H), 2.60-2.50 (m, 4H), 2.23 (s, 6H), 1.64 (s, 3H), 1.01 (m, 6H). 步驟2 _ ( 2 R ) - 2 -「4 -（ 9 -淳-2 -二乙胺田甚-3 -申某-赛駢 -1 6 9 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） --------------------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 0900 A7 B7 五、發明說明GW) 「2 - 3-b 卜啤吩-4-基)—_ζ_2_^_5·Τ„Ξΐ·Μ·ϋ 氣基 1二 I 里.__·.酯— (請先閱讀背面之注意事項再填寫本頁) 仿例49步驟6之方法，由4- ( 9-溴-2-二乙胺甲基-3- 甲基-萘駢[2 , 3 - b】-B富盼-4 -基卜2，6 -二甲酚酚（0 · 9 克，1.8?毫莫耳），（S) -2-羥基-3-苯丙酸甲酯（〇*67克，3.73毫莫耳），三苯_(0*98克，3.73毫莫耳：），偶氮二羧酸二乙酯（0 · 5 9毫升，3 * 7 3毫莫耳）及無水苯（1 0毫升），於87 °C下反應6小時可製得標題化合物之固體（〇 · 4 6 克，3 8 % ) : N M R ( D M S 0 - d 6 ) : 5 8.19 (d, 1H), 7.66-7.61 (m, 1H), 7.47-7.45 (m, 2H), 7.34 (d, 4H), 7.32-7.26 (ra, 1H), 7.00 (d, 2H), 4.80 (t, 1H), 3.74 (s, 2H), 3.58 (s, 3H), 3.36-3.25 (m, 2H), 2.55 (q, 4H), 2.24 (s, 3H), 2.19 (s, 3H), 1.59 (s, 3H), 1.03 (t, 6H); MS(+ESI): [M+H]% 1 溴間位素式樣，644/646; Anal. Calc, for C36H38BrN03S: C, 67.07 H, 5.94, N, 2.17. Found: C, 66.73, H, 5.93, N, 2.15. 步驟 3 ( 2R) -2-R-(卜海-2-二乙甲基- Γ 2 , 3 - b Ί - Β窜盼- 4· -某）- 2 * 6 二氫基—Ί - 3 Ί-SlM— 經濟部智慧財產局員工消費合作社印製I Ester Cinnamon 0 B 1 Step Race-Some & Second (Please read the notes on the back before filling out this page) A I 2-Step Ear 49 Mo 2 2 Imitation 60 French Method_1 | 之Jujube 0 Chlorine Diospermum 1 Bell 6 6 Large 1 5 Pairs of Lithium A. 4. grams printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, 2 N-dimethylformamide (2 drops), 2 , 3-dimethyl-5-benzylbenzophene (14.6 g, 72.2 millimoles), tin (IV) nitride (7.75 ml, 66.2 millimoles), and anhydrous di Made from methyl chloride (300 ml) and oil (24.4 g), which can be used without purification. Example 4 The method of step 2 from (9) to (2 -fluorenyl-4, 5-dimethylforman-3 -yl)-(4-methylaminophenyl) -formamidine 1 (22.4 g), tribromide Boron (17.1 ml, 180.9 mmol) and dichloromethane (120 ml) were prepared. The residue was acetic anhydride (7.4ffll, 78.4 mraol), Bit 聢 58.1 and dichloromethane 4 0 0 ml. Example 49 , Step 3 treatment to obtain 9.83 g of solid, 45.5%): NMR (DMSOd6): δ 8.48 (s, 1Η), 7.97 (d, J = 8 Hz, lH) f 7.50-7.33 (mt3H), 7.27 ( s, iH), 121 (s, 2H) * 2.40 (s, 3H), 2.36 (sf 3H) t 2.19 (s, 3H), 1.58 ($, 3H); MS (+ APC1): tM-PHJ 361. -1 8 7--------- Order · -------- · This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) Employees ’Consumption of Intellectual Property Bureau, Ministry of Economic Affairs Cooperative printed clothing 510900 A7 __ B7 V. Description of the invention (from) Step 2 B. Pan 2 1 2 —mm-dimethyl-Saipan "?. H 1-gft 2 · 4 2 base. JL · 2-2 Shenmou Zhu B§ Method of Example 4 9 Step 4 using 4- (2,3-dimethyl-naphthalenepyrene [233-b, p-pan-4-yl) -2-methylphenyl ester (5 0 g ^ 13.9 mol), ferric chloride (0.11 g, 0.68 mol ), Bromine (14.3 ml in 1.07 ketochloride (15.3 mmol), and dichloromethane (63 ml) can be prepared (5.44 g, 90.7%) Title compound: NMR (DMSO-d6): δ 8.20 (d, J = 9 Hz, 1Η), 7.65 (ddd, J = 2, 6, 8 Hz, 1H), 7.52-7.42 (m, 2H), 7.30 ( s, 1H), 7.23 (s, 2H), 2.43 (s, 3H), 2.36 (s, 3H), 2.20 (s, 3H). 1.56 (s, 3H); MS (EI): [M +], 1 Bromine isotope pattern, 438 ^: Anal · Calc · for C23H19B ^ 2S: C, 62.87, Η, 4.36 · ΝFaunck Example 8 6 Ethyl-acid dioxin i-dimo-2 -diamine methyl- 3 -Shenmou- 棻骈「2 ▲ 3-h 1-Bt Pan--4-yl 1-2. Β-Germanium Ester ester Step 1 Acetic acid 4-(9-? Xin 2-bromo Shenmou -3 -Shenmou-Zhe_2, 3-b 1 zM-Pan-4-yl 1-2 > ft-Dishenumate ester 4 Example 9 Method of step 4, using acetic acid 4-(2- Diethylamine methyl-3 -methyl-Ceamidine [2,3-b] -blaze-4-yl) -2,6-dimethylphenyl ester (10.0 g, 26.7 mmol), Ferric chloride (0.23 g, 1.42 mmol), bromine (1.51 ml in dichloromethane (38 ml), 29.4 mmol), and dichloromethane (231 mmol ) To obtain 4- (9-bromo-2,3-dimethyl-naphthalene) acetate [2,3 -b and p-phen-4 -kib 2,6-dimethylphenyl ester (6 · G8 g, 55%) and yellow solid of the title compound (1.60 g) · NMR (DMSO-d6): δ 8.28 (m, 1H), 7.62-7.56 (m, 2H), 7.41-7.37 (m, 1H) , 7.06 (s, 2H), 4.70 (s, 2H), 2.42 (s, 3H), 2.24 (s, 6H), 1.72 (s, 3H); MS (EI): [M +], 2 bromine isotope pattern, 530/532/534; Anal · Calc, for C24H20Br2O2S: C, 54.15, H, 3.79, N, 0.00. Found: C, 53; 81, H, 3.61, N, 0.10. —168— This paper size applies to China Standard (CNS) A4 specification (210 x 297 mm) -------------------- Order --------- ^ — ^ w— (Please Read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7 V. Description of the invention (Step 2 7, 酦 -4- (Ώ- 张 -2-Diethylamine dimethyl -盖 — 骈 — Γ 2. 3-b 卜 _ hope-4-a 1-2 t 6 dimethyl dimethyl rudolate acetate-4- (9-bromo-2-bromomethyl-3 -methyl- Naphthalene [2,3-b] -blazepan-4-ylb 2,6-dimethylbenzoate (1.21 g, 2.27 mmol) was treated with diethylamine (0.71 L, 6. 82 mmol), potassium sulfonate (0.94 g, 6. 82 mmol) and Ν, Ν - dimethylformamide (1 2 J mL). At room temperature for 1 hour, pour water (250 ml), filter and wash with water. Air-drying yielded the title compound as a yellow solid (lt13 g, 94 · 5¾): NMR (DMS0- (i6): 3 8.19 (d, lH), 7.66-7.61 (m, 1H), 7.47 (d, 2 Η), 7.13 (s, 2H), 3.73 (s, 2H), 2.58-2.52 (q, 4H), 2.40 (s, 3H), 2.16 (s, 6H), 1.61 (s, 3H), 1.02 (t , 6H); MS (EI): [M +], 1 bromine isotope pattern, 523-525; Anal · Calc · for C28H30BrNO2S: C, 64.12, H, 5.77, N, 2.67. Found: C, 63.30, H, 5.67 , N, 2.55. Example 87 2- "4- (9-Zhang-2-diethylamine Shenmou-3_methyl-trophocyanine" 2 * 3-1 > 1-11 2 · 6- 二申茉气其 -3_ 荣丙 _ Step 1 4-(9 -Zhang-?-Di ^ aminomethyl'3-甲某-赛 Γ 2, 3-h 1-B 4-A 1-2 · fi-Dishenol method 49 step 5 method, using 4-(9-bromo-2-diethylamine methyl-3-methyl-naphthalene hydrazone [2, 3-b Bu B sphenphen-4-yl] -2, 6-dimethylphenyl ester (1.1 3 g, 2.15 mmol), K0Η solution (2 6 58 ml of 1N solution, 2. 58 mmol) , Tetrahydrofuran (28 ml), and methanol (19 ml) to obtain the title compound as a yellow solid (1.0 g, 96sl%): NMR (DMS0-d6): < y 8.47 (s, 1H), 8.17 ( d, 1H), 7.64-7.59 (m, 1H), 7.55-7.45 (m, 1H), 7.45-7.39 (m, 1H), 6.90 (s, 2H), 3.72 (s, 2H), 2.60-2.50 (m, 4H), 2.23 (s, 6H) , 1.64 (s, 3H), 1.01 (m, 6H). Step 2 _ (2 R)-2-"4-(9 -Chun-2 -Diethylamine Tianshi-3 -Shenmou-Sakai-1 6 9-This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) -------------------- Order ------- --- line (please read the precautions on the back before filling this page) 0900 A7 B7 V. Description of the invention GW) "2-3-b Bu beerphen-4-yl) — _ζ_2 _ ^ _ 5 · Τ„ Ξΐ · Μ ·气 __ · .ester in gaseous 1-I — (Please read the precautions on the back before filling this page) The method in step 6 of Example 49 is based on 4- (9-bromo-2-diethylamine methyl- 3-methyl-naphthalenepyrene [2, 3-b] -B Fupan-4-kib 2,6-xylenol (0.9 g, 1.8? Moles), (S) -2- Methyl hydroxy-3-phenylpropionate (0 * 67 g, 3.73 mmol), triphenyl- (0 * 98 g, 3.73 mmol): diethyl azodicarboxylate (0.59 Ml, 3 * 73 mmol) and anhydrous benzene (10 ml), reacted at 87 ° C for 6 hours to obtain the title compound as a solid (0.46 g, 38% ): NMR (DMS 0-d 6): 5 8.19 (d, 1H), 7.66-7.61 (m, 1H), 7.47-7.45 (m, 2H), 7.34 (d, 4H), 7.32-7.26 (ra, 1H), 7.00 (d, 2H), 4.80 (t, 1H), 3.74 (s, 2H), 3.58 (s, 3H), 3.36-3.25 (m, 2H), 2.55 (q, 4H), 2.24 (s , 3H), 2.19 (s, 3H), 1.59 (s, 3H), 1.03 (t, 6H); MS (+ ESI): [M + H]% 1 bromo isotopic pattern, 644/646; Anal. Calc, for C36H38BrN03S: C, 67.07 H, 5.94, N, 2.17. Found: C, 66.73, H, 5.93, N, 2.15. Step 3 (2R) -2-R- (卜海 -2-Diethylmethyl -Γ 2, 3-b Ί-Βpanpan-4 · -a)-2 * 6 Dihydro-—Ί-3 Ί-SlM— Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs

仿例49步驟7之方法，由（2R)-2-[4-(9 -溴-2-二乙胺甲基-3-甲基-葉駢[2, 3 -b]-睹盼-4-基）-2，6-二甲苯氧基] -3-苯丙酸甲酯（0·35克，0·98毫莫耳），K0H溶液（1.95毫升之1 Ν溶液，1. 9 5毫莫耳），四氫呋喃（9毫升），及甲醇 (3毫升）可製得標題化合物固體（〇·35克，>100%): NMR (DMSO-d6): δ 12.90 (br s, 1H), 8.19 (d, 1H), 7.66-7.61 (m, 1H), 7.50-7.43 (m, 2H), 7.37-7.31 (m, 4H), 7.28-7.24 (m, 1H), 7.00 (s, 2H), 4.72 (t, 1H), 3.74 (s, 2H), 3.38-3.25 (m, 2H), 2.60-2.53(q, 4H), 2·26 (s, 3H)，2.23 (s, 3H)，1·60 (s, 3H), 1.02(tf6H); MS(-ESI): f 1 溴同位素式樣，628/630: AmU· Ctt丨c, for C35H36BrN03S: C，66.66, H，5·75, N, 2·22· Found: C, 66.95, Η, 5·99, N, 2·26· -170^ 本紙張尺度適用中國國家標準（CNS)A4規格(210 x 297公釐） 510900 A7 B7_ 五、發明說明（啊）例88 (2 R) - 2 -「4 - ( 9 -海-2 -二乙胺申基-3 -甲某-棻駢「2 . 3 - b Ί 二座—盼- 4 -某）- 2 . 6 -二異丙茱氫某1-3- ¾丙酴仿例8 7 5用適當起始物，得標題化合物，黃色固體（D M S 0 - d6): δ 13.00 (br s, 1H), 8.18 (d, 1H), 7.63-7.60 (m, 1H), 7.46-7.44 (m, 2H), 7.36-The method of step 7 of Example 49 was performed from (2R) -2- [4- (9-bromo-2-diethylaminemethyl-3-methyl-phyllene [2, 3 -b] -watchpan-4 -Yl) -2,6-xylyloxy] -3-phenylpropanoic acid methyl ester (0.35 g, 0.98 mmol), K0H solution (1.95 ml of 1 N solution, 1. 9 5 mmol Mol), tetrahydrofuran (9 ml), and methanol (3 ml) to obtain the title compound solid (0.35 g, > 100%): NMR (DMSO-d6): δ 12.90 (br s, 1H), 8.19 (d, 1H), 7.66-7.61 (m, 1H), 7.50-7.43 (m, 2H), 7.37-7.31 (m, 4H), 7.28-7.24 (m, 1H), 7.00 (s, 2H), 4.72 (t, 1H), 3.74 (s, 2H), 3.38-3.25 (m, 2H), 2.60-2.53 (q, 4H), 2.26 (s, 3H), 2.23 (s, 3H), 1. · 60 (s, 3H), 1.02 (tf6H); MS (-ESI): f 1 bromine isotope pattern, 628/630: AmU · Ctt 丨 c, for C35H36BrN03S: C, 66.66, H, 5.75, N, 2 · 22 · Found: C, 66.95, Η, 5.99, N, 2.26 · -170 ^ This paper size is applicable to China National Standard (CNS) A4 (210 x 297 mm) 510900 A7 B7_ V. Description of the invention (Ah) Example 88 (2 R)-2-"4-(9 -Hai-2 -Diethylaminoshenyl-3 -A-Mou- 棻骈" "2. 3-b Ί Two-Pan-4 -M )-2. 6 -Diisopropanyl Hydroxide 1-2-3 ¾Propanamine Example 8 7 5 Using the appropriate starting material, the title compound was obtained as a yellow solid (DMS 0-d6): δ 13.00 (br s, 1H), 8.18 (d , 1H), 7.63-7.60 (m, 1H), 7.46-7.44 (m, 2H), 7.36-

7.24 (m, 5H), 7.06 (s, 2H), 4.46 (t, 1H), 3.71 (s, 2H), 3.38-3.34 (m, 2H), 3.25 (d, 2H), 2.54 (q, 4H), 1.52 (s, 3H), 1.13 (d, 6H), 1.06 (d, 6H), 1.00 (t, 6H); MS(-ESI): [M-H]·，1 溴間位素式樣，684/686; Anal· Calc· for C39H44BrN03S: C， 68.21, H, 6.46, N, 2.04. Found: C, 68.04, H, 6.52, N, 1.92; HPLC 顯示主成分（9 7 · 4 % )。 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 -17 1- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）公. 申請曰期- 1 〇 . 案號類別乙 17义餐«/ (以上各欄由本局填註）鉱5U 年月曰 •险止兄 C4 510900 4 % 為* ^專利説明書 η 口 J用於治療抗胰島素征及高血糖症 , 之苯駢瞎吩類，苯駢呋喃類及吲n朵類發明新型名稱7.24 (m, 5H), 7.06 (s, 2H), 4.46 (t, 1H), 3.71 (s, 2H), 3.38-3.34 (m, 2H), 3.25 (d, 2H), 2.54 (q, 4H) , 1.52 (s, 3H), 1.13 (d, 6H), 1.06 (d, 6H), 1.00 (t, 6H); MS (-ESI): [MH] ·, 1 bromo isotopic pattern, 684/686 ; Anal · Calc · for C39H44BrN03S: C, 68.21, H, 6.46, N, 2.04. Found: C, 68.04, H, 6.52, N, 1.92; HPLC showed the main component (97 · 4%). (Please read the precautions on the back before filling out this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs -17 1- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm). Application. Issue-1 〇. Case No. Category B 17 Meal Symptoms and Hyperglycemia, New Names of Inventions of Benzophenones, Benzofurans and Indole

BENZOTHIOPHENES, BENZOFURANS, AND INDOLES 英文 USEFUL IN THE TREATMENT 〇F INSULIN RESISTANCE AND HYPERGLYCEMIA 姓名國籍發明創作人住、居所姓名 (名稱） be特Di塔· ΓΟ狄·安Μ 桕 WJJMne 瑞E.林ne林le E y爾1達d 國國國 a tc, Γ § a ___ 咨J +Λ Α巨：Μ , _寒. 1 2 3 12 3 奇Γ1 1瑞et尼BENZOTHIOPHENES, BENZOFURANS, AND INDOLES English USEFUL IN THE TREATMENT 〇F INSULIN RESISTANCE AND HYPERGLYCEMIA尔 1 达 d 国国国 a tc, Γ § a ___ Consult J + Λ Α 巨： Μ, _ 寒. 1 2 3 12 3 Odd Γ1 1 Rui et al.

A 虎 ft § 5 1 1 2 道號14 樹13庭瑰路利玫爾瑪市尼市飛寇飛西市西倫倫倫勞達勞 8 5 8 4 7 4 6 0 6 8 8 8 ο ο ο 4— J1 4— 西西西澤澤澤紐紐紐國國國美美美 12 3 惠氏公司（Wyeth) 裝訂線經濟部中央標隼局員工消費合作社印製國籍美國三、申請人住、居所 (事務所）代表人姓名美國紐澤西州07940曼迪森5吉拉德農場依岡 E.貝格（Egon E. Berg) 本紙張尺度適用中國國家標隼（CNS〉A4規格（210 X 297公釐） 510900 A7 ea.8,3〇 __B7_____ 五、發明說明（"）例1 2 · ,4-(2,3-二甲基-9-苯磺醯某-龚駢『2,3邛1-噻吩-_1^1^ (請先閱讀背面之注意事項再填寫本頁) 於含甲礦酸-4 - （ 9 -碑-2久S·- —甲奈餅[2， 3-b] 吩-4 -基）-苯醋（t) · G 2 0克，1 · 2 2毫莫耳）及氯化銅1 (:0 β 1 9 2克，1 · 3 4毫莫耳）之無水N， N -二甲基甲酿胺，於乾氬氣下加人蹲吩（〇 · 2 7 ϋ毫升，2 · G 8毫莫耳）及微細N a 0 Η粉（0 · 1 G 7克，2 · G 8毫莫耳）。於室溫下携拌8小時，加至水中，以1 0% H C 1酸化，並以***萃取。結合萃取液，過濾，水洗並濃縮。將黃色固體溶於11 鸣烷（8毫升），加入2_5NNa0H(4.5毫升）。密封瓶子並加熱至1 Q 2 °C。反應後（由薄層層析指示），冷卻牵室溫，以水稀釋並以H C 1酸化。以***萃取，結合萃取液以矽膠，移除溶劑。將吸附物驟層析（9 ϋ / 1 0 〜8 5 / 1 5石油_/乙酸乙酯），追加苯及石油醚可得標A Tiger ft § 5 1 1 2 Road No. 14 Tree 13 Court Rose Road Limelma City Ni Fei Fei Fei Xi Xilun Lun Lundao 8 5 8 4 7 4 6 0 6 8 8 8 ο ο ο 4— J1 4—Western Jersey, New Zealand, New Zealand, New Zealand, Gome, and the United States 12 3 Wyeth Gutter Binding Line Ministry of Economic Affairs Central Standards Bureau Employee Consumption Cooperatives Print Nationality US III. Applicant's Residence, Residence (Office) Egon E. Berg, Mandison 5 Gillard Farm, New Jersey 07940, USA This paper size is applicable to Chinese national standard (CNS> A4 size (210 X 297 mm) 510900 A7 ea.8 , 3〇__B7 _____ V. Explanation of the invention Example 1 2 ·, 4- (2,3-dimethyl-9-benzenesulfonium-gong-gong 骈 "2,3 邛 1-thiophene-1_1 ^ 1 ^ (Please read the notes on the back before filling out this page) In Methanoic Acid-4-(9-Monument-2 Jiu S · --- Cannai Cake [2, 3-b] phen-4 -yl)- Anhydrous N, N-dimethyl of phenyl vinegar (t) · G 2 0 g, 1.2 2 mmoles and copper chloride 1 (: 0 β 1 9 2 g, 1. 34 mmoles) Methylamine, add squalene under dry argon (0.27 ml, 2 · G 8 mmol) And fine N a 0 powder (0 · 1 G 7 g, 2 · G 8 mmol). Stir at room temperature for 8 hours, add to water, acidify with 10% HC 1 and extract with ether. Combine the extracts, filter, wash with water and concentrate. Dissolve the yellow solid in 11-octane (8 mL) and add 2_5NNa0H (4.5 mL). Seal the bottle and heat to 1 Q 2 ° C. After the reaction (indicated by TLC) ), Cool to room temperature, dilute with water and acidify with HC 1. Extract with ether, combine the extract with silica gel, remove the solvent. Chromatograph the adsorbate (9 ϋ / 1 0 ~ 8 5/1 5 petroleum_ / Ethyl acetate), additional benzene and petroleum ether can be awarded

題化合物之白色固體（〇 · 4 2 6克，8 5 % ) : N M R (DMSO-d6);6 9.70 (s, 1H, OH), 8.40 (d, J = 8 Hz, 1H), 7.56-7.51 (m, 2H), 7.44-7.40 (m, IH), 7·25·7·12 (m, 5H)，7.02 (d, J = 7 Hz，2H)，6.93 (d，J = 9 Hz，2H)， 3.67 (s, 3H), 1.62 (s, 3H); MS(EI): [M+] 412 (100%); Anal. calc, for C26H20OS2: C, 75.69, H, 4.89, N, 0.00. Found C, 74.98, H, 4.86, N, 0.13. 經濟部智慧財產局員工消費合作社印製例1 3 2« 6-二海-4-（2· 3-二甲某 _9_ 苯礎酿基-赛 Srf「2· 3 - b Ί ~ 陳盼-4-基）-齡於含4- (2， 3-二甲基-9-苯礎酿基-萘駢[2， 3-b]-B塞吩-4 -基）-酚（〇 · 4 1 4克，1 · 0 0毫莫耳），及乙酸鉀（ 0 · 9 8 2克，1 0 · 0毫莫耳）之冰醋酸（2 · 5 0毫升），於1 0分 -83-本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） Λ7 B7 51〇9〇〇 i、發明說明（97 ) ί.2^ .二4二二滢二. 3 -上JjiJg ..败·^ 強-.)一二 2 二胤農蓋丄二仿例3 0之方法，由2 -漠—4 - ( 9 -漠_ 2， 3 —二甲银*"萊餅 f 2，；卜b 1 -幃吩—4 -难_) - 6 -硝酚（例2 1 )及（S ) - 2 -羥银〜3 ~苯丙酸甲酯（例2 5 )可製得臼色固體·：熔點2 4 3 ~ 245°C: NMR (DMS0-d6); δ 11.30 (broad s, 1H), 8.23, 8.22 (2d, J = 3 Hz, 1H), 8.06, 8.04 (2d, J = 3 Hz, 1H), 7.95 (t, J = 2, 1H), 7.68 (m, 1H), 7.56-7.50 (m, 1H), 7·45 (d, J = 8 Hz, 1Η)，7.34·7·24 (m，6H), 5.28 5.22 (2t, J = 6Hz，IH)，3,40-3.23 (m, 2H), 4.82 (d, J = 6 Hz, 1H), 2.46 (s, 3H), 1.59 1.57 (2s, 3H); MS (+FAB): 2 溴同位素式樣 653,655,657; Anal· Calc· for C29H21Br2N05S:C, 53·15, H, 3.23, N, 2.14. Found: C, 53.77, H, 3.73, N, 2.04. 例39 2 - - 生二」Q -》京一 2 · 3 --二甲某-縈！^ 「2 . 3 - b_ 1 - HI： P分-4 -基）步驟 1 : 2-遝丙猓-4. - ( ? · 3 -二甲基-_藶 -Al.n.Ht- 阶 ~ 4 ~ .¾ ) -聯仿例4 3之方法，由3 -異丙锥-對大阔番醇酸（3 · 0克， 1 G · 5 毫莫耳：，R. N - 3 3 5 3 7 - 7 8 - 9 )，草 _ 氯（1 · 7 毫升，1 9 · 5 毫莫耳），N， N -二甲基甲醯胺（2滴），2， 3 -二甲基- 5 -芣{1寒吩（4 · 0克，1 9 · 8毫莫耳），氯化錫（I V ) (2.1 毫升，18. 2毫莫耳），及無水一氣甲院（65笔：升），可製得標題化合物之暗紅色油（6 · 5克），其可不經純化育接使用。仿例4 9步驟2之方法，由（2 -节棊-4 , 5 -二甲蕋-瞎吩 - 3 -难）-(3 -異丙基-4 -甲氧苯棊）-甲酮（G · 5克，1 7 . 8毫莫耳），三溴化硼（9 . 4毫升，9 9毫莫耳），及二氯甲烷（7 5毫升） -9 9 - 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） _____________ (請先閱讀背面之注意事項再填寫本頁) 訂-----^----線' 經濟部智慧財產局員工消費合作社印製 510900 ί A7 _B7_ 五、發明說明) 仂例4 ί)步驟7之方法，由（R ) - 2 - [ 4 - ( 9 -溴_ 2， 3 -二甲棊-萘駢[2 , 3 - h ]-卩本吩-4 -基）-2 -環戊苯氣基1 - 3 -苯丙酸甲酯（〇 · 1 8克，0 · 3毫莫珲），K 0 Η溶液（0 · 3 9毫升之1 Ν溶液，0 · 3 9毫冥再），四氫呋喃（6毫升），及甲醇（2毫升）可製得標題化合物之白色固體（G . 1 5克， 8 4%) : NMR (DMS0-d6) : d 13.12(寬 s , 1 Η ) , 8 . 18 - 8 . 1 5 (m,lH) ,7.64-7.58(m,lH) ,7.47-7.Z2(m,7H) ,7.10-7.40 (ΐϊΐ,2Η),0.89-β.86(ηι,]. Η),5.10-5.03(πι,1Η),3.32-3.18 (m , 3 H) , 2.40(s,3H),1.90(ra,lH),1.76(m,lH),1.70- 1 . 3 (3 ( m含二單線ί 1 · 5 1和].· 5 0 (旋轉異構物），9 H ); M S ( - f： S I ) : [ Η - Η ],溴同位素式樣，5 9 7 / 5 9 9 ·，A n a 1 . Calc, for C34H31Br03S : C,68.11, H, 5 . 21 , N, 0.0 0. Found : C , G 8. 10 , H, 5 . 3 1 , N ,0 .01〇例48 (R) -2 -「2 -湟-4- (9 -溴-2· 3-二甲基-赛駢「2. 3-bl 本紙張尺度適用中國國家標準（CNS〉A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) I ϋ n n n VI I n 1 ^ · —1 I— n n mmmM— ϋ— I n -睞P分-4 -甚）-6 -璟戍荣Μ某1 Ί茱丙酪步驟 1 2 - - 4 - （ 9 - ?尊一 2 . 3 -二申基一蔡駢「2 . 3 - b 1 - H寒盼-4、甚）-6-環戍酚於含2_環丨戈基-4- ( 9-漠-2， 3_二甲基-蔡駢[2， 3-b] -嘑吩-4 -蕋）-酚（2 . 0克，4 · 4毫莫耳）及乙酸鉀（4 · 4 克，44. 3毫莫耳）之冰醋酸（GG毫升），於17分内滴加入含溴（（1.2 7毫升，5 .3毫莫耳）之冰醋酸（8毫升）。稀釋以冰醋酸（.2 G毫升）。於室溫下攪拌2小時後倒至水（5 0 0毫升）中。以***（2 5 G毫升）萃取再以*** -117- 經濟部智慧財產局員工消費合作社印製 510900 A7 B7 三苯五、發明說明 -2 -羥基-3 -苯丙酸甲酯（1」2克，6 · 2毫莫耳）膦Μ . Π 0克，G ·]毫莫耳），偶氮二羧酸二乙酯（〇 · 9 6 毫升，（；.1毫莫耳）及無水苯（2 · 5毫升），於8 i) DC下反應3天可製得（2 R.) - 2 -丨4 - ( 9 -溴-2， 3 -二甲基-萘駢 [2，3 - h ]_ P窜吩-4 -基）-2 -丙基苯氣基]-3 _苯丙酸甲醋 (0 . 2 3克）之固體，其可不經純化而使用。彷例4 9少驟7之方法，由（2 R ) - 2 - [ 4 - ( 9 -溴-2 , 3 - 二甲棊-萘駢[2， 3 _ b卜睹吩-4 _基）-2 -丙基苯氧基]-3 - 苯丙酸甲酯（〇·23克，（K3 9毫莫耳），Κ0Η溶液（0.93 毫升之溶液，0 · 9 3毫莫耳），四氫呋喃（4 · 6毫升），及足景甲醇可製得含檫題化合物黃色泡沫（0 · 1 7克，7 U )之均質溶液：NMR (DMSO-d6): δ 13.15 (br s，1Η)，8.18 (d，J = 3, 9 Ηζ，1Η), 7.67-7.59 (m, 1H), 7.50-7.23 (m, 7H), 7.52-7.40 (m, 2H), 6.88 (dd, J = 5, 8 Hz, 1H), 5.15-5.02 (m, 1H), 3.24 (m, 2H), 2.73-2.53 (m, 2H), 2.42 (s, 3H), 1.60-1.40 (m containing two singlets at δ 1.56 and 1.54,直生異構物，5H), 0.87 and 0.85 (two t，J = 7 Hz,直生異構物,3H); MS(EI): [M+]，1溴同位素式樣， 572/574. 例84 「9-溴-4-(4-甲氧基-3,5-二甲苯基）1-3-甲基-萘駢1~2,3-1)1 請先閱讀背 © 之注意事項再填頁經濟部智慧財產局員工消費合作社印製酷甲酸乙飄 I— 某 4 盼 0 將 ( 升氯« 駢，萘克 1 ο 基 2 甲 ί 二醚 3-香，0 2 I 甲溴二吩 if 耳莫毫硫升毫耳莫毫基 t 丙烷異甲二氯，二 ) 水耳無莫及毫，次 2 洗水醚乙以釋稀〇時小 2 拌攪下 °c 9 於鹽 ο }食 {升以胺毫並乙24, 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）White solid of the title compound (0.426 g, 85%): NMR (DMSO-d6); 6 9.70 (s, 1H, OH), 8.40 (d, J = 8 Hz, 1H), 7.56-7.51 (m, 2H), 7.44-7.40 (m, IH), 7.25 · 7 · 12 (m, 5H), 7.02 (d, J = 7 Hz, 2H), 6.93 (d, J = 9 Hz, 2H ), 3.67 (s, 3H), 1.62 (s, 3H); MS (EI): [M +] 412 (100%); Anal. Calc, for C26H20OS2: C, 75.69, H, 4.89, N, 0.00. Found C, 74.98, H, 4.86, N, 0.13. Printed by the Consumer Property Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 1 3 2 «6- 二海 -4- (2 · 3- 二甲某 _9_ benzene-based brewing base-sai Srf 「2 · 3-b Ί ~ Chen Pan-4-yl） -Ling Yu containing 4- (2, 3-dimethyl-9-benzene base brewing group-naphthalene 骈 [2, 3-b] -B plug Phen-4 -yl) -phenol (0.414 g, 1.0 mmol) and potassium acetate (0.92 g, 10 · 0 mmol) in glacial acetic acid (2 · 50 ml), at 10 minutes-83- This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) Λ7 B7 510090i, description of the invention (97) ί 2 ^. 2 4 2 2 2 2. 3-on JjiJg .. defeated ^ strong-.) 1 2 2 2 2 farmer cover 2 second example 3 0 method, from 2-desert-4-(9- _ 2, 3 —dimethyl silver * " Rice cake f 2 ,; b 1 -phene-4 -difficult _)-6-nitrophenol (example 2 1) and (S)-2-hydroxysilver ~ 3 ~ Methyl phenylpropionate (example 25) can be prepared as a solid colored solid: melting point 2 4 3 ~ 245 ° C: NMR (DMS0-d6); δ 11.30 (broad s, 1H), 8.23, 8.22 (2d, J = 3 Hz, 1H), 8.06, 8.04 (2d, J = 3 Hz, 1H), 7.95 (t, J = 2, 1H), 7.68 (m, 1H), 7.56-7.50 (m, 1H), 7 · 45 (d, J = 8 Hz, 1Η), 7.34 · 7 · 24 (m, 6H), 5.28 5.22 (2t, J = 6Hz, IH), 3,40-3.23 (m, 2H), 4.82 (d , J = 6 Hz, 1H), 2.46 (s, 3H), 1.59 1.57 (2s, 3H); MS (+ FAB): 2 bromine isotope pattern 653,655,657; Anal · Calc · for C29H21Br2N05S: C, 53 · 15, H , 3.23, N, 2.14. Found: C, 53.77, H, 3.73, N, 2.04. Example 39 2--Born 2 "Q-" Jingyi 2 · 3-Erjia Mou- 萦! ^ "2. 3-b_ 1-HI: P fraction -4-radical) Step 1: 2-Aminopropane-4.-(? · 3 -dimethyl-_ 苈 -Al.n.Ht- order ~ 4 ~ .¾)-The method according to Example 4 3, which consists of 3 -isopropylcone-p-glyoxylic acid (3.0 g, 1 G · 5 mmol :, R. N-3 3 5 3 7-7 8-9), grass_chlorine (1.7 ml, 19 · 5 mmol), N, N -dimethylformamide (2 drops), 2, 3-dimethyl-5 -芣 {1 Hanfen (4.0 g, 19 · 8 mmol), tin (IV) chloride (2.1 ml, 18.2 mmol), and anhydrous Yiqi Jiayuan (65 pens: liters) A dark red oil (6.5 g) of the title compound can be prepared, which can be used without purification and breeding. The method of Step 2 of Example 4 9 is obtained from (2-Section 棊 -4, 5 -dimethylformamidine-blind Phen-3 -difficult)-(3-isopropyl-4 -methoxyphenylhydrazone) -methanone (G · 5 g, 17.8 mmol), boron tribromide (9.4 ml, 9 9 millimoles), and dichloromethane (75 ml) -9 9-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) _____________ (Please read the precautions on the back before filling in this Page) Order ----- ^ ---- line ' Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 510900 ί A7 _B7_ V. Description of the invention) Example 4 ί) The method of step 7 consists of (R)-2-[4-(9 -bromo_ 2, 3 -dimethylamine棊 -naphthalene 骈 [2, 3-h]-卩 benphen-4-yl) -2-cyclopentylphenylamino 1-3 -phenylpropanoic acid methyl ester (0.18 g, 0.3 mmol) ), K 0 Η solution (0.39 ml of 1 N solution, 0.39 mmol), tetrahydrofuran (6 ml), and methanol (2 ml) to obtain the title compound as a white solid (G. 1 5 g, 8 4%): NMR (DMS0-d6): d 13.12 (width s, 1 Η), 8.18-8.15 (m, lH), 7.64-7.58 (m, lH), 7.47- 7.Z2 (m, 7H), 7.10-7.40 (ΐϊΐ, 2Η), 0.89-β.86 (η,). Η), 5.10-5.03 (π, 1Η), 3.32-3.18 (m, 3 H), 2.40 (s, 3H), 1.90 (ra, lH), 1.76 (m, lH), 1.70- 1.3 (3 (m with two single lines ί 1 · 5 1 and]. · 5 0 (rotomers) , 9 H); MS (-f: SI): [Η-Η], bromine isotope pattern, 5 9 7/5 9 9 ·, Ana 1. Calc, for C34H31Br03S: C, 68.11, H, 5. 21 , N, 0.0 0. Found: C, G 8. 10, H, 5. 3 1, N, 0.011 Example 48 (R) -2 -``2-湟 -4- (9 -Bromo-2 · 3-Dimethyl-Symphony "2. 3-bl This paper size applies to Chinese national standards (CNS> A4 size (210 X 297 mm) (Please read the precautions on the back before filling out this page) I ϋ nnn VI I n 1 ^ · —1 I— nn mmmM— ϋ— I n-favor P points -4-even) -6-璟戍 ΜΜ 1 1 ruta casein step 1 2--4-(9-? Zunyi 2.3-Di Shenji-Cai Yan "2.3-b 1-H Hanpan-4, even) -6-Cyclophenol containing 2_ring 丨 Goki-4- (9- Desert- 2, 3_dimethyl-Ceamidine [2, 3-b] -methylphen-4 -fluorene) -phenol (2.0 g, 4.4 mmol) and potassium acetate (4.4 g, 44 3 mmol of glacial acetic acid (GG ml), dropwise add bromine ((1.2 7 ml, 5.3 mmol) of glacial acetic acid (8 ml) over 17 minutes. Dilute with glacial acetic acid (.2 G ml). After stirring at room temperature for 2 hours, it was poured into water (500 ml). Extract with diethyl ether (2 5 G ml) and then diethyl ether-117- Printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs 510900 A7 B7 Triphenyl V. Description of the Invention-2 -Hydroxy-3 -phenylpropionate methyl ester G, 6.2 mmol) Phosphine M. Π 0 g, G ·] mmol), diethyl azodicarboxylate (0.96 ml, (; .1 mmol) and anhydrous benzene (2 · 5 ml), reacted at 8 i) DC for 3 days to obtain (2 R.)-2-丨 4-(9 -bromo-2, 3 -dimethyl-naphthalenepyrene [2,3- h] _P-Phenyl-4-yl) -2-propylphenylamino] -3_phenylpropanoic acid methyl ester (0.23 g), which can be used without purification. The method of Example 4 9 and Step 7 consists of (2 R)-2-[4-(9 -bromo-2, 3-dimethylfluorene-naphthalene [2, 3 _ b 卜睹 phen-4 _ group) -2-propylphenoxy] -3-methyl phenylpropionate (0.23 g, (K3 9 mmol), K0） solution (0.93 ml of solution, 0.93 mmol), tetrahydrofuran ( 4 · 6 ml) and Potent Methanol can prepare a homogeneous solution containing the title compound as a yellow foam (0.17 g, 7 U): NMR (DMSO-d6): δ 13.15 (br s, 1Η), 8.18 (d, J = 3, 9 Ηζ, 1Η), 7.67-7.59 (m, 1H), 7.50-7.23 (m, 7H), 7.52-7.40 (m, 2H), 6.88 (dd, J = 5, 8 Hz , 1H), 5.15-5.02 (m, 1H), 3.24 (m, 2H), 2.73-2.53 (m, 2H), 2.42 (s, 3H), 1.60-1.40 (m containing two singlets at δ 1.56 and 1.54, Orthoisomers, 5H), 0.87 and 0.85 (two t, J = 7 Hz, orthoisomers, 3H); MS (EI): [M +], 1 bromine isotope pattern, 572/574. Example 84 "9-Bromo-4- (4-methoxy-3,5-xylyl) 1-3-methyl-naphthalene fluorene 1 ~ 2,3-1) 1 Please read the precautions of the back © before filling Page Intellectual Property Bureau, Ministry of Economic Affairs, Employee Consumer Cooperative Printed Ethyl Acetate I—some 4 0 will (liters of chlorine «骈, naphthyl 1 ο base 2 methyl diether 3-fragrant, 0 2 I methyl bromide diphenone if mol sulfide liter mol mol yl t propane isomethyl dichloride, di) water There is no more than ears, 2 times washing with ether B to release dilute 0 o small 2 stirring under ° c 9 in salt ο} food {liter to amine milli and B 24, this paper size applies Chinese National Standard (CNS) A4 Specifications (210 X 297 mm)

Claims

々、申請專利範圍第88 1 07532號「可用於治療抗胰島素症及高血糖症之苯駢噻吩類，苯駢呋喃類及吲哚類」專利案（9 1年5月修正）六申請專利範圍： 1. 一種如下式I之化合物，々、 Patent application No. 88 1 07532 “Phenylthiophene, benzofuran and indole which can be used for the treatment of insulin resistance and hyperglycemia” (Amended in May 2011) 6 Scope of patent application : 1. A compound of the following formula I,

A爲氫； B及D各爲氫，鹵素，CV6烷基，C3_8環烷基，硝基，胺基，或-NRiCC^R13 ; Rla爲氫，或CV6烷基； R1 爲氫，CV6 烷基或-CH'C^R1’ ； R1’爲氫或CV6烷基； E爲S或〇； 510900 ^、申請專利範圍 X爲氫，鹵素，Cm烷基或苯磺醯基； Y爲氫，鹵素，烷基或NR3R3a ; R3及R3a各爲氫或CV6烷基； C爲氫或OR4 ; R4爲氫，烷基或-CH ( R5) W ; R5爲氫，CV6烷基或苯CV6烷基； W爲C〇2R6，其中R6爲氫，ίν6烷基，或苯基；或W爲 -C〇NR6bCHR7bC〇2R6，其中R6b，R7b,R6各爲氫，CV6烷基，或苯基； Z1及Z2可以二烯單位共形成- CH = CH-CH = CH ; 或其製藥容許鹽。 2. 如申請專利範圍第1項之化合物，其爲（R ) -2-[2,6-二溴-4- ( 9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）苯氧基]-3- 苯丙酸或其製藥容許鹽。 3. 如申請專利範圍第1項之化合物，其爲（R) -2-[2-溴-4- (9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-6-乙基-苯氧基]-3-苯丙酸或其製藥容許鹽。 4. 如申請專利範圍第1項之化合物，其爲（R ) -2-[4- ( 9-溴-2，3-二甲基-萘駢[2,3-b]噻吩-4-基）-2,6-二甲基-苯氧基]-3-苯丙酸或其製藥容許鹽。 5. 如申請專利範圍第1項之化合物，其爲（R) -2-[4- ( 9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-2-氟苯氧基]-3-苯丙酸或其製藥容許鹽。 6. 如申請專利範圍第1項之化合物，其爲[4- ( 9-溴-2,3-二 510900 t、申請專利範圍甲基-萘駢[2,3-b]噻吩-4-基）-2,6-二異丙苯氧基]-乙酸或其製藥容許鹽。 7. 如申請專利範圍第1項之化合物，其爲（R ) -2-[2-溴- 4- (9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-6-第二丁基-苯氧基]-3-苯丙酸或其製藥容許鹽。 8. 如申請專利範圍第1項之化合物，其爲（R) 溴-4- (9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-6-異丙基-苯氧基]-3-苯丙酸或其製藥容許鹽。 9. 如申請專利範圍第1項之化合物，其爲（R) -2-[2-溴-4- (9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-2-環戊基-苯氧基]-3-苯丙酸或其製藥容許鹽。 10. 如申請專利範圍第1項之化合物，其爲（R) -2-[4- ( 9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4_基）-6-異丙基-苯氧基]-3-苯丙酸或其製藥容許鹽。 11. 如申請專利範圍第1項之化合物，其爲（R ) -2-[4- ( 9-溴-2,3-二甲基萘駢[2,3-b]噻吩-4-基）-2-環戊基-苯氧基]-3- 苯丙酸或其製藥容許鹽。 12. 如申請專利範圍第1項之化合物，其爲（R ) -2-[2,6-二溴-4- ( 2,3-二甲基-9-苯磺醯基-萘駢[2,3-b]噻吩-4-基）-苯氧基]-3-苯丙酸或其製藥容許鹽。 13. 如申請專利範圍第1項之化合物，其爲（R) _2-[2,6-二溴-4- ( 9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-苯氧基]-3-苯丁酸或其製藥容許鹽。 14. 如申請專利範圍第1項之化合物，其爲（S) -2-[2,6-二A is hydrogen; B and D are each hydrogen, halogen, CV6 alkyl, C3-8 cycloalkyl, nitro, amine, or -NRiCC ^ R13; Rla is hydrogen, or CV6 alkyl; R1 is hydrogen, CV6 alkyl Or -CH'C ^ R1 '; R1' is hydrogen or CV6 alkyl; E is S or 0; 510900 ^, the scope of patent application for X is hydrogen, halogen, Cm alkyl or benzenesulfonyl; Y is hydrogen, halogen , Alkyl or NR3R3a; R3 and R3a are each hydrogen or CV6 alkyl; C is hydrogen or OR4; R4 is hydrogen, alkyl or -CH (R5) W; R5 is hydrogen, CV6 alkyl or benzene CV6 alkyl; W is C02R6, where R6 is hydrogen, ννalkyl, or phenyl; or W is -C0NR6bCHR7bC〇2R6, where R6b, R7b, and R6 are each hydrogen, CV6 alkyl, or phenyl; Z1 and Z2 Diene units can be co-formed-CH = CH-CH = CH; or a pharmaceutically acceptable salt thereof. 2. For example, the compound in the scope of patent application No. 1 is (R) -2- [2,6-dibromo-4- (9-bromo-2,3-dimethyl-naphthalene} [2,3- b] thiophen-4-yl) phenoxy] -3-phenylpropionic acid or a pharmaceutically acceptable salt thereof. 3. For example, the compound in the scope of patent application No. 1 is (R) -2- [2-bromo-4- (9-bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] thiophene 4-yl) -6-ethyl-phenoxy] -3-phenylpropionic acid or a pharmaceutically acceptable salt thereof. 4. For example, the compound in the scope of patent application No. 1 is (R) -2- [4- (9-bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] thiophen-4-yl ) -2,6-dimethyl-phenoxy] -3-phenylpropionic acid or a pharmaceutically acceptable salt thereof. 5. The compound as claimed in item 1 of the scope of patent application, which is (R) -2- [4- (9-bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] thiophen-4-yl ) -2-fluorophenoxy] -3-phenylpropionic acid or a pharmaceutically acceptable salt thereof. 6. For example, the compound in the scope of patent application No. 1 is [4- (9-bromo-2,3-di510900 t), and the scope of patent application is methyl-naphthalenepyrene [2,3-b] thiophen-4-yl ) -2,6-Dicumyloxy] -acetic acid or a pharmaceutically acceptable salt thereof. 7. The compound as claimed in item 1 of the scope of patent application, which is (R) -2- [2-bromo-4 (9-bromo-2,3-dimethyl-naphthalene} [2,3-b] thiophene 4-yl) -6-second butyl-phenoxy] -3-phenylpropionic acid or a pharmaceutically acceptable salt thereof. 8. The compound as claimed in item 1 of the scope of patent application, which is (R) bromo-4- (9-bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] thiophen-4-yl)- 6-isopropyl-phenoxy] -3-phenylpropionic acid or a pharmaceutically acceptable salt thereof. 9. The compound as claimed in item 1 of the scope of patent application, which is (R) -2- [2-bromo-4- (9-bromo-2,3-dimethyl-naphthalene} [2,3-b] thiophene 4-yl) -2-cyclopentyl-phenoxy] -3-phenylpropionic acid or a pharmaceutically acceptable salt thereof. 10. The compound as claimed in item 1 of the scope of patent application, which is (R) -2- [4- (9-bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] thiophene-4-yl ) -6-isopropyl-phenoxy] -3-phenylpropionic acid or a pharmaceutically acceptable salt thereof. 11. For example, the compound in the scope of patent application No. 1 is (R) -2- [4- (9-bromo-2,3-dimethylnaphthalenepyrene [2,3-b] thiophen-4-yl) 2-cyclopentyl-phenoxy] -3-phenylpropionic acid or a pharmaceutically acceptable salt thereof. 12. For example, the compound in the scope of patent application No. 1 is (R) -2- [2,6-dibromo-4- (2,3-dimethyl-9-benzenesulfonyl-naphthalene) [2 , 3-b] thiophen-4-yl) -phenoxy] -3-phenylpropionic acid or a pharmaceutically acceptable salt thereof. 13. For the compound in the scope of patent application item 1, which is (R) _2- [2,6-dibromo-4- (9-bromo-2,3-dimethyl-naphthalene} [2,3-b ] Thiophen-4-yl) -phenoxy] -3-phenylbutyric acid or a pharmaceutically acceptable salt thereof. 14. For the compound in the scope of patent application item 1, it is (S) -2- [2,6- 二

510900 六、申請專利範圍溴-4- ( 9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4·基）-苯氧基卜 4-苯丁酸或其製藥容許鹽。 15_如申請專利範圍第1項之化合物，其爲2-[2,6-二溴-4-( 9-溴-3-甲基-2-嗎啉-4-基甲基-萘駢[2,3-b]噻吩-4-基）-苯氧基]-3-苯丙酸或其製藥容許鹽。 16.如申請專利範圍第1項之化合物，其爲（R ) -2-[2,6-二溴-4- ( 2,3-二甲基-9-苯磺醯基萘駢[2,3-b]噻吩-4-基）-苯氧基]-丙酸或其製藥容許鹽。 17·如申請專利範圍第1項之化合物，其爲[2-溴-4-( 9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-2-硝苯氧基]-3-苯丙酸或其製藥容許鹽。 18. 如申請專利範圍第1項之化合物，其爲2,6-二溴-4-( 9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）·酚或其製藥容許鹽。 19. 如申請專利範圍第1項之化合物，其爲2-溴-4- ( 9-溴-2，3-二甲基-萘駢[2,3-b]噻吩-4-基）-2-硝酚或其製藥容許鹽。 20. 如申請專利範圍第1項之化合物，其爲（R ) -2-[2,6-二溴-4- ( 9-溴-2-二乙胺甲基-3-甲基-萘駢[2,3-b]噻吩-4-基）苯氧基]-3-苯丙酸或其製藥容許鹽。 21. 如申請專利範圍第1項之化合物，其爲（R) -2-[2,6-二溴-4- ( 2,3-二甲基-萘駢[2,3-b]-呋喃-4_基）-苯氧基苯丙酸或其製藥容許鹽。 22·如申請專利範圍第1項之化合物，其爲（2R) -2-[4- ( 9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-2,6-二異丙苯氧 510900 六、申請專利範圍基]-3-苯丙酸或其製藥容許鹽。 23. 如申請專利範圍第丨項之化合物，其爲（R) _2_[4_ ( 9_ 溴-2,3 -二甲基萘駢[2,3-b]噻吩-4-基）_2,6 -二乙苯氧基卜3 苯丙酸或其製藥容許鹽。 24. 如申請專利範圍第1項之化合物，其爲{ ( 2R) -2_[4_ ( 9_ 溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-2,6-二甲苯氧基]·^ 苯丙醯胺基卜乙酸或其製藥容許鹽。 25. 如申請專利範圍第1項之化合物，其爲{ ( 2R) -2-[4_ ( 9· 溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-2,6_二乙苯氧基]_3· 苯丙醯胺基}乙酸或其製藥容許鹽。 26如申請專利範圍第1項之化合物，其爲（2R) -2-[4- ( 9-溴-2,3-二甲基-奈駢[2,3-b]噻吩-4-基）-苯氧基卜3 -苯丙酸或其製藥容許鹽。 27_如申請專利範圍第1項之化合物，其爲（2S ) -2-[4- ( 9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4·基）-2，6-二甲基-苯氧基]-3-苯丙酸或其製藥容許鹽。 2δ·如申請專利範圍第1項之化合物，其爲{ ( 2R) -2-[4- ( 2,3-二甲基-萘餅[2,3-b]I®吩-4 -基）-2,6 -二乙苯氧基]-3 -苯丙醯胺胺}乙酸或其製藥容許鹽。 29.如申請專利範圔第1項之化合物’其爲（R ) -2 - [ 4 - ( 9 -溴 -2,3-二甲基-萘駢[2,34]-呋喃-4_基）-2,6-二乙苯氧基]-3-苯丙酸或其製藥容許鹽。犯如申請專利範圍第1項之化合物，其爲（R) -2-[2-環戊基 -4-(2,3-二甲基-萘駢[2，％1)]暖吩-4-基）-苯氧基]-3-苯丙510900 6. Scope of patent application: bromo-4- (9-bromo-2,3-dimethyl-naphthalene [2,3-b] thiophen-4 · yl) -phenoxybenzene 4-phenylbutyric acid or its Pharmaceuticals allow salt. 15_ The compound according to item 1 of the scope of patent application, which is 2- [2,6-dibromo-4- (9-bromo-3-methyl-2-morpholin-4-ylmethyl-naphthalene] [ 2,3-b] thiophen-4-yl) -phenoxy] -3-phenylpropionic acid or a pharmaceutically acceptable salt thereof. 16. The compound according to item 1 of the scope of patent application, which is (R) -2- [2,6-dibromo-4- (2,3-dimethyl-9-benzenesulfonylnaphthalene) [2, 3-b] thiophen-4-yl) -phenoxy] -propionic acid or a pharmaceutically acceptable salt thereof. 17. The compound according to item 1 of the scope of patent application, which is [2-bromo-4- (9-bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] thiophen-4-yl)- 2-nitrophenoxy] -3-phenylpropionic acid or a pharmaceutically acceptable salt thereof. 18. The compound as claimed in item 1 of the scope of patent application, which is 2,6-dibromo-4- (9-bromo-2,3-dimethyl-naphthalenefluoren [2,3-b] thiophen-4-yl ) Phenol or its pharmaceutically acceptable salt. 19. The compound according to item 1 of the scope of patent application, which is 2-bromo-4- (9-bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] thiophen-4-yl) -2 -Nitrophenol or a pharmaceutically acceptable salt thereof. 20. The compound according to item 1 of the scope of patent application, which is (R) -2- [2,6-dibromo-4- (9-bromo-2-diethylaminemethyl-3-methyl-naphthalene) [2,3-b] thiophen-4-yl) phenoxy] -3-phenylpropionic acid or a pharmaceutically acceptable salt thereof. 21. The compound as claimed in item 1 of the scope of patent application, which is (R) -2- [2,6-dibromo-4- (2,3-dimethyl-naphthalenepyrene [2,3-b] -furan -4_yl) -phenoxyphenylpropionic acid or a pharmaceutically acceptable salt thereof. 22. The compound according to item 1 of the scope of patent application, which is (2R) -2- [4- (9-bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] thiophen-4-yl ) -2,6-Dicumyloxy 510900 6. Patent application scope] 3-Phenylpropionic acid or its pharmaceutically acceptable salt. 23. For example, the compound in the scope of application for patent No. 丨 is (R) _2_ [4_ (9_ bromo-2,3-dimethylnaphthalenepyrene [2,3-b] thiophen-4-yl) _2,6- Diethylphenoxyb 3 phenylpropionic acid or a pharmaceutically acceptable salt thereof. 24. If the compound in the scope of application for item 1 is {(2R) -2_ [4_ (9_ bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] thiophen-4-yl)- 2,6-xylyloxy] · ^ phenylpropanylaminoacetic acid or a pharmaceutically acceptable salt thereof. 25. If the compound in the scope of application for item 1 is {(2R) -2- [4_ (9 · bromo-2,3-dimethyl-naphthalene [2,3-b] thiophen-4-yl ) -2,6_diethylphenoxy] _3. Phenylpropanylamino} acetic acid or a pharmaceutically acceptable salt thereof. 26. The compound according to item 1 of the scope of patent application, which is (2R) -2- [4- (9-bromo-2,3-dimethyl-naphthalene [2,3-b] thiophen-4-yl) -Phenoxyb 3-phenylpropionic acid or a pharmaceutically acceptable salt thereof. 27_ The compound according to item 1 of the scope of patent application, which is (2S) -2- [4- (9-bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] thiophene-4 · yl ) -2,6-dimethyl-phenoxy] -3-phenylpropionic acid or a pharmaceutically acceptable salt thereof. 2δ · As the compound in the first item of the patent application scope, which is {(2R) -2- [4- (2,3-dimethyl-naphthalene cake [2,3-b] I®phen-4 -yl) -2,6-diethylphenoxy] -3 -amphetamine amine} acetic acid or a pharmaceutically acceptable salt thereof. 29. The compound according to item 1 of the patent application, which is (R) -2-[4-(9 -bromo-2,3-dimethyl-naphthalene [2,34] -furan-4_yl ) -2,6-Diethylphenoxy] -3-phenylpropionic acid or a pharmaceutically acceptable salt thereof. The compound that violates the scope of patent application No. 1 is (R) -2- [2-cyclopentyl-4- (2,3-dimethyl-naphthalenepyrene [2,% 1)] nonphen-4 -Yl) -phenoxy] -3-phenylpropyl

510900 六、申請專利範圍酸或其製藥容許鹽。 3丄如申請專利範圔第1項之化合物，其爲（R) _2_[4_ (卜溴 -2,3·二甲基-萘駢[2,3-b]噻吩-4-基）-2-環戊基-苯氧基]-丙酸或其製藥容許鹽。 32如申請專利範圍第丨項之化合物，其爲（r) （ 2> 二甲基-萘駢[2,3_b]噻吩-4-基）-2-乙基-苯氧基μ3_苯丙酸或其製藥容許鹽。 33如申請專利範圍第丨項之化合物，其爲2-溴_4- ( 2,3_二甲基-萘駢[2,3-b]呋喃-4-基）-6-乙酚或其製藥容許鹽。 34如申請專利範圍第1項之化合物，其爲（R)_2-[2-溴2,3_ 二甲基-萘駢[2,3-b]呋喃-4-基）-6-乙基-苯氧基苯丙酸或其製藥容許鹽。 35如申請專利範圍第1項之化合物，其爲（R) _2_[4_ ( 9-溴_ 2,3-二甲基-萘駢[2,3 -b]噻吩-4-基）-2-丙基-苯氧基卜3-苯丙酸或其製藥容許鹽。 36如申請專利範圍第1項之化合物，其爲（2R) -2-[4- ( 9-溴-2-二乙胺甲基-3-甲基-萘駢[2,3-b]噻吩-4-基）-2,6-二異丙基-苯氧基]-3-苯丙酸或其製藥容許鹽。 37.如申請專利範圍第1項之化合物，其爲4- ( 2，3-二甲萘駢 [2,3-13]噻吩-4-基）-酚；4-(9-溴-2,3-二甲萘駢[2,3-1)]噻吩 -4-基）-酚；4- ( 2,3-二甲基-9-苯磺醯基-萘駢[2,3-b]噻吩-4-基）-酚；2,6-二溴·4-( 2,3-二甲基-9·苯磺醯基-萘駢[2,3-b] 噻吩-4-基）-酚；4-( 9-溴-3-甲基-2-嗎啉-4-基）-甲萘駢[2,3-b] 噻吩-4-基）-酚；4-( 9-溴-2-二乙胺甲基-3-甲基-萘駢[2,3-b] 510900 t、申請專利範圍噻吩-4-基）-乙酸鹽；4- ( 9-溴-2-二乙胺甲基-3-甲基-萘駢[2,3-b]噻吩-4-基）-酚；2,6-二溴-4- ( 9-溴-2-二乙胺甲基-3-甲基-萘駢[2,3-b]噻吩-4-基）-酚；2,6-二溴-4- ( 9-溴 -3-甲基-2-嗎啉-4-基甲萘駢[2,3-b]噻吩-4-基）-酚；4- ( 9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-2-硝酚；2-胺基-4-(9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-酚；2-胺基-6-溴-4-(9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-酚；[2-溴-4- ( 9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-2-硝苯氧基]-乙酸；（1〇-2-[2,6-二溴-4-(9-溴-2,3-二甲基-萘駢[2,3-13] 噻嗯-4-基）-苯氧基]-丙酸；2-[2,6-二溴-4- ( 9-溴-3-甲基-2-嗎啉-4-基甲基-萘駢[2,3-b]噻吩-4-基）-苯氧基]-丙酸； 2-溴-4- ( 9-溴-2,3·二甲基-萘駢[2,3-b]噻吩-4-基）-6-異丙酚；（R) -2-[4- ( 2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-2-異丙苯氧基]-3-苯丙酸；（R ) -2-[2-環戊基-4- ( 2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-苯氧基]-3-苯丙酸；（R)-2-[4-( 2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-2,6-二甲苯氧基]-3-苯丙酸；（1〇-2-[4-(2,3-二甲基-萘駢[2,3-1)]噻吩-4-基）-2,6-二異丙苯氧基]-3-苯丙酸；（R) -2-[4- (2,3-二甲基-萘駢 [2,3-b]噻吩-4-基）-2-氟苯氧基]-3-苯丙酸；（R) -2-[4-(9-溴- 2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-2-乙基-苯氧基]-3-苯丙酸；3-溴-5- ( 9-溴- 2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-2-甲氧苯胺；或[3-溴-5- ( 9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-2-甲氧苯胺基]-乙酸；（2R) -2-[4 - ( 9-溴-2,3-二甲基-1-氧_1小萘駢[2,3-1)]噻吩-4-基）-2,6-二甲510900 6. Scope of patent application Acid or its pharmaceutically acceptable salt. 3) The compound according to item 1 of the patent application, which is (R) _2_ [4_ ([Bromo-2,3 · dimethyl-naphthalene] [2,3-b] thiophen-4-yl) -2 -Cyclopentyl-phenoxy] -propionic acid or a pharmaceutically acceptable salt thereof. 32 The compound according to item 丨 in the scope of patent application, which is (r) (2 > Or its pharmaceutically acceptable salt. 33. The compound according to item 丨 of the patent application scope, which is 2-bromo-4- (2,3-dimethyl-naphthalenepyrene [2,3-b] furan-4-yl) -6-ethylphenol or Pharmaceuticals allow salt. 34 The compound according to item 1 of the scope of patent application, which is (R) _2- [2-bromo2,3-dimethyl-naphthalenepyrene [2,3-b] furan-4-yl) -6-ethyl- Phenoxyphenylpropionic acid or a pharmaceutically acceptable salt thereof. 35 The compound according to item 1 of the scope of patent application, which is (R) _2_ [4_ (9-bromo-2,3-dimethyl-naphthalenepyrene [2,3- -b] thiophen-4-yl) -2- Propyl-phenoxyb 3-phenylpropionic acid or a pharmaceutically acceptable salt thereof. 36. The compound according to item 1 of the scope of patent application, which is (2R) -2- [4- (9-bromo-2-diethylaminemethyl-3-methyl-naphthalene} [2,3-b] thiophene -4-yl) -2,6-diisopropyl-phenoxy] -3-phenylpropionic acid or a pharmaceutically acceptable salt thereof. 37. The compound according to item 1 of the scope of patent application, which is 4- (2,3-dimethylnaphthalene [2,3-13] thiophen-4-yl) -phenol; 4- (9-bromo-2, 3-dimethylnaphthalenepyrene [2,3-1)] thiophen-4-yl) -phenol; 4- (2,3-dimethyl-9-benzenesulfonyl-naphthalenepyrene] [2,3-b] Thiophen-4-yl) -phenol; 2,6-dibromo · 4- (2,3-dimethyl-9 · benzenesulfonyl-naphthalene [2,3-b] thiophen-4-yl)- Phenol; 4- (9-bromo-3-methyl-2-morpholin-4-yl) -menaphthyl [2,3-b] thiophen-4-yl) -phenol; 4- (9-bromo- 2-diethylamine methyl-3-methyl-naphthalene [2,3-b] 510900 t, patent application scope thiophen-4-yl) -acetate; 4- (9-bromo-2-diethylamine Methyl-3-methyl-naphthalenepyrene [2,3-b] thiophen-4-yl) -phenol; 2,6-dibromo-4- (9-bromo-2-diethylaminemethyl-3- Methyl-naphthalenepyrene [2,3-b] thiophen-4-yl) -phenol; 2,6-dibromo-4- (9-bromo-3-methyl-2-morpholin-4-ylmenaphthalene骈 [2,3-b] thiophen-4-yl) -phenol; 4- (9-bromo-2,3-dimethyl-naphthalene 骈 [2,3-b] thiophen-4-yl) -2- Nitrophenol; 2-amino-4- (9-bromo-2,3-dimethyl-naphthalene [2,3-b] thiophen-4-yl) -phenol; 2-amino-6-bromo- 4- (9-bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] thiophen-4-yl) -phenol; [2-bromo-4- (9-bromo-2,3-di Methyl-naphthalenepyrene [2,3-b] thiophene- 4-yl) -2-nitrophenoxy] -acetic acid; (1〇-2- [2,6-dibromo-4- (9-bromo-2,3-dimethyl-naphthalene) [2,3 -13] thien-4-yl) -phenoxy] -propionic acid; 2- [2,6-dibromo-4- (9-bromo-3-methyl-2-morpholin-4-ylmethyl) -Naphthalenepyrene [2,3-b] thiophen-4-yl) -phenoxy] -propionic acid; 2-bromo-4- (9-bromo-2,3 · dimethyl-naphthalenepyrene [2, 3-b] thiophen-4-yl) -6-propofol; (R) -2- [4- (2,3-dimethyl-naphthalenepyrene [2,3-b] thiophen-4-yl) -2-cumyloxy] -3-phenylpropanoic acid; (R) -2- [2-cyclopentyl-4- (2,3-dimethyl-naphthalenepyrene [2,3-b] thiophene -4-yl) -phenoxy] -3-phenylpropanoic acid; (R) -2- [4- (2,3-dimethyl-naphthalenepyrene [2,3-b] thiophen-4-yl) -2,6-xylyloxy] -3-phenylpropanoic acid; (1〇-2- [4- (2,3-dimethyl-naphthalenepyrene [2,3-1)] thiophen-4-yl ) -2,6-diisopropylphenoxy] -3-phenylpropanoic acid; (R) -2- [4- (2,3-dimethyl-naphthalene} [2,3-b] thiophene-4 -Yl) -2-fluorophenoxy] -3-phenylpropanoic acid; (R) -2- [4- (9-bromo-2,3-dimethyl-naphthalene} [2,3-b] thiophene -4-yl) -2-ethyl-phenoxy] -3-phenylpropanoic acid; 3-bromo-5- (9-bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] Thien-4-yl) -2-methoxyaniline; or [3-bromo-5- (9-bromo-2,3-dimethyl-naphthalene} [2,3-b ] Thiophen-4-yl) -2-methoxyaniline] -acetic acid; (2R) -2- [4-(9-bromo-2,3-dimethyl-1-oxo_1 small naphthalene) [2 , 3-1)] thiophen-4-yl) -2,6-dimethyl

510900 六、申請專利範圍基-苯氧基]-3-苯丙酸；（R) -2-[4- ( 2,3-二甲基-萘駢[2,3-b] 噻吩-4-基）-2，6-二乙基-苯氧基]-3-苯丙酸；4- (2，3-二甲基-萘駢[2,3-b]呋喃-4-基）-2,6-二乙酚；4-[4- ( 9-溴- 2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-2-環戊基-苯氧基]-丁酸； 2- 環戊基-4- ( 2,3-二甲基-萘駢[2，3-b]呋喃-4-基）-酚；2-環戊基-4-( 2,3_二甲基-萘駢[2,3-b]呋喃-4-基）-乙酸苯酯； (R) -2-[4-(9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-2-乙基-苯氧基]-3-苯丙酸；4-[2-溴-4-( 2,3-二甲基-萘駢[2，3-b] 呋喃-4-基）-6-乙基-苯氧基]-丁酸；4-[2-溴-4- ( 2,3-二甲基-萘駢[2,3-b]呋喃-4-基）-6-乙基-苯氧基]-丁醯胺；4-( 2,3-二甲基-萘駢[2,3-b]呋喃-4-基）-2-乙酚；[9-溴-4- ( 4-甲氧基-3,5-二甲苯基）-3-甲基-萘駢[2，3-b]噻吩-2-基]-乙酸甲酯；4- ( 9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-2-甲基-乙酸苯酯；4- ( 9-溴-2-乙胺甲基-3-甲基-萘駢[2,3-b]噻吩-4-基）-2,6-二甲基-乙酸苯酯；2-[4- (9-溴-2-二乙胺甲基- 3- 甲基-萘駢[2,3-b]噻吩-4-基）-2，6-二甲基-苯氧基卜3-苯丙酸；或其製藥容許鹽。 3S如申請專利範圍第1項之化合物，其爲乙酸4- ( 2,3-二甲基-萘駢[2,3-1)]噻吩-4-基）-苯酯；乙酸4-(9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-苯酯；甲磺酸4-(2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-苯酯；甲磺酸4-(9-碘-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-苯酯；乙酸4- ( 9-溴-2-氯甲基-3-甲基-萘駢[2,3-b]噻吩-4-基）-苯酯；（R) -2-[2,6·二溴-4- ( 9-溴-2,3-二甲基-萘駢[2,3-b]噻吩-4-基）-苯氧基]-510900 6. Application scope of patent-Phenyloxy] -3-phenylpropanoic acid; (R) -2- [4- (2,3-Dimethyl-naphthalenepyrene [2,3-b] thiophene-4- Group) -2,6-diethyl-phenoxy] -3-phenylpropanoic acid; 4- (2,3-dimethyl-naphthalenepyrene [2,3-b] furan-4-yl) -2 , 6-Diethylphenol; 4- [4- (9-Bromo-2,3-dimethyl-naphthalene [2,3-b] thiophen-4-yl) -2-cyclopentyl-phenoxy ] -Butyric acid; 2-cyclopentyl-4- (2,3-dimethyl-naphthalene [2,3-b] furan-4-yl) -phenol; 2-cyclopentyl-4- (2 , 3-Dimethyl-naphthalenepyrene [2,3-b] furan-4-yl) -phenyl acetate; (R) -2- [4- (9-Bromo-2,3-dimethyl-naphthalene骈 [2,3-b] thiophen-4-yl) -2-ethyl-phenoxy] -3-phenylpropanoic acid; 4- [2-bromo-4- (2,3-dimethyl-naphthalene骈 [2,3-b] furan-4-yl) -6-ethyl-phenoxy] -butyric acid; 4- [2-bromo-4- (2,3-dimethyl-naphthalene] [2 , 3-b] furan-4-yl) -6-ethyl-phenoxy] -butanidine; 4- (2,3-dimethyl-naphthalenepyrene [2,3-b] furan-4- Yl) -2-ethylphenol; [9-bromo-4- (4-methoxy-3,5-xylyl) -3-methyl-naphthalenepyrene [2,3-b] thiophen-2-yl ] -Methyl acetate; 4- (9-bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] thiophen-4-yl) -2-methyl-phenylacetate; 4- (9 -Bromo-2-ethylamine methyl-3- -Naphthalenepyrene [2,3-b] thiophen-4-yl) -2,6-dimethyl-phenylacetate; 2- [4- (9-bromo-2-diethylaminemethyl-3- Methyl-naphthalenepyrene [2,3-b] thiophen-4-yl) -2,6-dimethyl-phenoxyb 3-phenylpropanoic acid; or a pharmaceutically acceptable salt thereof. 3S The compound according to item 1 of the scope of patent application, which is 4- (2,3-dimethyl-naphthalenepyrene [2,3-1)] thiophen-4-yl) -phenyl acetate; 4- (9 -Bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] thiophen-4-yl) -phenyl ester; 4- (2,3-dimethyl-naphthalenepyrene] [2,3 -b] thiophen-4-yl) -phenyl ester; 4- (9-iodo-2,3-dimethyl-naphthalene} [2,3-b] thiophen-4-yl) -phenyl ester; 4- (9-bromo-2-chloromethyl-3-methyl-naphthalenepyrene [2,3-b] thiophen-4-yl) -phenyl ester; (R) -2- [2,6 · di Bromo-4- (9-bromo-2,3-dimethyl-naphthalenepyrene [2,3-b] thiophen-4-yl) -phenoxy]-

510900 、申請專利範圍 3-本丙酸甲醋，[3 -漠-5- (9 -漠-2,3-二甲基-蔡餅[2,3-b]嚷吩-4-基）-2·羥苯基]-胺甲酸第三丁酯；9-溴-4- ( 3-漠·甲氧基-5-硝苯基）-2,3-二甲基-萘駢[2,3-b]噻吩；或[3-漠 (9-溴-2,3-二甲基·萘駢[2,3-b]噻吩-4-基）-2-甲氧基、苯月安基]-乙酸甲酯。 39. —種用於有其需要之動物體中調控葡萄糖量之醫藥組$ 物，含有如申請專利範圍第1項定義之式I化合物或#_ 藥容許鹽爲活性成分，以及製藥容許載劑。 40. —種用於有其需要之動物治療經由抗胰島素症或高血糖症仲介之代謝異常之醫藥組成物’含有如申請專利範圍第1 項定義之式I化合物或其製藥容許鹽爲活性成分，及製藥容許載體。510900 、 Applicable patent scope 3- methyl propionate, [3- Mo-5- (9-Mo-2,3-dimethyl-Cai cake [2,3-b] fluoren-4-yl)- 2 · Hydroxyphenyl] -carbamic acid third butyl ester; 9-Bromo-4- (3-Mo · methoxy-5-nitrophenyl) -2,3-dimethyl-naphthalene [2,3 -b] thiophene; or [3- Mo (9-bromo-2,3-dimethylnaphthalene [2,3-b] thiophen-4-yl) -2-methoxy, benzalanyl] -Methyl acetate. 39. — A pharmaceutical composition for regulating the amount of glucose in an animal in need, containing a compound of formula I or #_ a drug-acceptable salt as an active ingredient and a pharmaceutical-acceptable carrier . 40. —A pharmaceutical composition for treating metabolic disorders via anti-insulinism or hyperglycemia via use of an animal in need thereof, which contains a compound of formula I or a pharmaceutically acceptable salt thereof as defined in item 1 of the scope of patent application as an active ingredient , And pharmaceutical carriers.