TW415947B - N-benzylazolium derivatives having antifungal activity - Google Patents

Abstract

N-Benzylazolium derivatives of the general formula (I), wherein Q is the remainder of an azole compound of the formula II, possessing antifungal activity; Z is nitrogen or methine; R1 and R2 are each independently a hydrogen atom or a group -OY [in which Y is a group easily hydrolyzable under physiological condition]; R3 and R4 are each independently a hydrogen or halogen atom, C1-C5 alkyl, C1-C5 alkoxy, carboxy or methoxycarbonyl; and methoxycarbonyl; and X- is a pharmaceutically acceptable anion, as well as salts, hydrates or solvates of the compounds of the general formula (I) have antifungal properties.

Description

經濟部中央標隼局員工消费合作社印策 415947 第861丨乃23號專利申請案 中文說明書修正頁(88年丨2月） 五、發明説明（1 ) 雖然目前有數種吐化合物使用於黴菌病，但其在整體程 度上均未符合必須之臨床要求條件’意即抵抗包括散佈性 錄菌病之主要系統黴菌病之功效、安全性及口服或非經腸 配方。特別是’對於嚴重系統黴菌病之治療而言，唑化合 物之非輕腸投藥之要求是漸増的。在市場上以及在發展中 之大邵份吨化合物’均為鬲度親脂性分子，這使得非經腸 配方有所困難= 内藤（衛材之U S 5，6 4 8，3 7 2以及相關案E p 〇 6 6 7 3 4 6 ) 概括地敘述了吐類衍生物，其中Ri及r2為鹵素，R3為甲 基（參照第j欄6 4行’烷基）’ W為含有超過1個雜原子之 芳香環（第2欄，2至5行），-(X)r-(Y)m-Z代表4_氰苯基 (參照m = 〇，X為具有1或更多許代基之芳香環，z為氰 基*欄/行：1 / 6 5 - 6 6以及2 / 6 - 7，1 6以及1 9 )。這些唑類 竹生物與現存之字基偶氮鑌（b e n z y 1 a ζ ο 1 i u m)衍生物之 不同處在於其中Q為Q1，且不具任意經取代之苄基-N+， X —部分。 傑森之US 4,017,631概括地敘述了咪唑鹽，其中A為 二鹵苯基，B為二鹵芊基（第1欄，54行以及58至59行）且 D為任意經取代之芊基（第二欄第65行）。由於傑森之芊基 團D不具有本發明實施例7中（R〇 9-3559)所包含之醋酸 基R1，該咪唑鹽與Ro 9-3559之咪唑鹽產物不同。 韋根之DE 2531031 及 BASF之 FR 1519132 敘述了 N-芊基咪唑鹽，其中該正辛基或正癸基R(韋根）以及該C12-C|6-烷基r3(basf)則與本發明中之Q基不同。 -4 - 本紙張尺度適用中國國家標準（CNS ) A4规格（210X297公釐） i i 訂 ί /Μ (诗先閱讀背面之注意事項再填寫本頁) 經濟部中央標隼局員工消费合作社印策 415947 第861丨乃23號專利申請案 中文說明書修正頁(88年丨2月） 五、發明説明（1 ) 雖然目前有數種吐化合物使用於黴菌病，但其在整體程 度上均未符合必須之臨床要求條件’意即抵抗包括散佈性 錄菌病之主要系統黴菌病之功效、安全性及口服或非經腸 配方。特別是’對於嚴重系統黴菌病之治療而言，唑化合 物之非輕腸投藥之要求是漸増的。在市場上以及在發展中 之大邵份吨化合物’均為鬲度親脂性分子，這使得非經腸 配方有所困難= 内藤（衛材之U S 5，6 4 8，3 7 2以及相關案E p 〇 6 6 7 3 4 6 ) 概括地敘述了吐類衍生物，其中Ri及r2為鹵素，R3為甲 基（參照第j欄6 4行’烷基）’ W為含有超過1個雜原子之 芳香環（第2欄，2至5行），-(X)r-(Y)m-Z代表4_氰苯基 (參照m = 〇，X為具有1或更多許代基之芳香環，z為氰 基*欄/行：1 / 6 5 - 6 6以及2 / 6 - 7，1 6以及1 9 )。這些唑類 竹生物與現存之字基偶氮鑌（b e n z y 1 a ζ ο 1 i u m)衍生物之 不同處在於其中Q為Q1，且不具任意經取代之苄基-N+， X —部分。 傑森之US 4,017,631概括地敘述了咪唑鹽，其中A為 二鹵苯基，B為二鹵芊基（第1欄，54行以及58至59行）且 D為任意經取代之芊基（第二欄第65行）。由於傑森之芊基 團D不具有本發明實施例7中（R〇 9-3559)所包含之醋酸 基R1，該咪唑鹽與Ro 9-3559之咪唑鹽產物不同。 韋根之DE 2531031 及 BASF之 FR 1519132 敘述了 N-芊基咪唑鹽，其中該正辛基或正癸基R(韋根）以及該C12-C|6-烷基r3(basf)則與本發明中之Q基不同。 -4 - 本紙張尺度適用中國國家標準（CNS ) A4规格（210X297公釐） i i 訂 ί /Μ (诗先閱讀背面之注意事項再填寫本頁) 415947 .... A 861丨7223跳I利巾請案 丨>7 双 _中文說明耸脩正阶88年12 i B7 ,，補古 五、發明説明（ 希啦斯之υ S 4，2 6 7，丨7 9概括地敘述了呤 _ 4類何生物，其 (請先Μ讀背面之注意事項再填寫本頁) 中Ar為：函苯基且㈣取代基為丨·甲丙基（第3摘， 47至48行）之式⑴之5_氧基三也基_4_屢（第3攔，第5 行）。這些吐類衍生物與本發明實施例 * J I , 2 , J ( R 〇 9 - 3577，R〇 9-3631 以及 R〇 9-3588)之 kj 从好 '卞基***鹽產 物不同處在於其不具有一經取代之苄基· N + N ，X邵分。 與内藤及希爾斯之咪峻及三峻衍生物相較，本發明之N _ 爷基咪唑鹽以及N-爷基***鹽具有優越之水溶性，其極適 於經皮吸收。 與傑森·韋根及B A S F之咪唑鹽相較，本發明之咪吐鹽 則與其在結構上顯不相同。 本發明係關於可用以治療系統黴菌病且適於口服及特別 是非經腸投藥之新穎水溶性唑化合物，其製造方法，含有 彼等之抗真菌組合物及治療黴菌病之方法。 更特定言之，本發明係關於以通式⑴表示之新穎w全化合 物 經濟部中央樣準局員工消費合作社印衷 其中Revised Page of Chinese Manual for Patent Application 415947 No. 23 of Patent Application No. 23 of the Central Bureau of Standards of the Ministry of Economic Affairs of the People's Republic of China (February 88 丨 February) 5. Description of the Invention (1) Although there are currently several types of vomiting compounds used in mycosis, However, it does not meet the necessary clinical requirements in the whole degree, which means the efficacy, safety and oral or parenteral formula against major systemic mycosis including disseminated bacillary disease. In particular, for the treatment of severe systemic mycosis, the requirement for non-light bowel administration of azole compounds is gradually increasing. In the market as well as in the development, the large amount of compounds' are all lipophilic molecules, which makes parenteral formulations difficult = Naito (US 5,6 4 8, 3 7 2 and related cases) E p 〇 6 6 7 3 4 6) General description of spit derivatives, where Ri and r2 are halogen, R3 is methyl (refer to column j, line 6 and 4 'alkyl)' W is containing more than one impurity Atom aromatic ring (column 2, lines 2 to 5),-(X) r- (Y) mZ represents 4-cyanophenyl (refer to m = 〇, X is aromatic ring with 1 or more oxo groups, z Are cyano * columns / rows: 1/6 5-6 6 and 2/6-7, 16 and 19). The difference between these azole-type bamboo organisms and the existing zirconyl azo (b e n z y 1 a ζ ο 1 i um) derivatives is that Q is Q1 and does not have any substituted benzyl-N +, X- moiety. Jason US 4,017,631 describes imidazole salts in general, where A is a dihalophenyl group, B is a dihalofluorenyl group (columns 1, lines 54 and 58 to 59) and D is any substituted fluorenyl group (number Second column, line 65). Since the hydrazone group D of Jason does not have the acetic acid R1 included in Example 7 of the present invention (R0 9-3559), the imidazole salt is different from the imidazole salt product of Ro 9-3559. The DE 2531031 of Wiegand and the FR 1519132 of BASF describe N-fluorenimidazole salts. The n-octyl or n-decyl R (Wiegand) and the C12-C | 6-alkyl r3 (basf) are the same as The Q group in the invention is different. -4-This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) ii Order / LM (Read the notes on the back of the poem first and then fill out this page) Central Consumers Bureau of the Ministry of Economy Staff Consumer Cooperative Cooperative Imprint 415947 No. 861 丨 It is the revised page of the Chinese specification of Patent Application No. 23 (February 丨 February 88) 5. Description of the invention (1) Although there are currently several kinds of vomiting compounds used for mycosis, they do not meet the necessary clinical requirements on the whole. Requirement 'means the efficacy, safety, and oral or parenteral formula against major systemic mycosis including disseminated bacillary disease. In particular, for the treatment of severe systemic mycosis, the requirement for non-light bowel administration of azole compounds is gradually increasing. In the market as well as in the development, the large amount of compounds' are all lipophilic molecules, which makes parenteral formulations difficult = Naito (US 5,6 4 8, 3 7 2 and related cases) E p 〇 6 6 7 3 4 6) General description of spit derivatives, where Ri and r2 are halogen, R3 is methyl (refer to column j, line 6 and 4 'alkyl)' W is containing more than one impurity Atom aromatic ring (column 2, lines 2 to 5),-(X) r- (Y) mZ represents 4-cyanophenyl (refer to m = 〇, X is aromatic ring with 1 or more oxo groups, z Are cyano * columns / rows: 1/6 5-6 6 and 2/6-7, 16 and 19). The difference between these azole-type bamboo organisms and the existing zirconyl azo (b e n z y 1 a ζ ο 1 i um) derivatives is that Q is Q1 and does not have any substituted benzyl-N +, X- moiety. Jason US 4,017,631 describes imidazole salts in general, where A is a dihalophenyl group, B is a dihalofluorenyl group (columns 1, lines 54 and 58 to 59) and D is any substituted fluorenyl group (number Second column, line 65). Since the hydrazone group D of Jason does not have the acetic acid R1 included in Example 7 of the present invention (R0 9-3559), the imidazole salt is different from the imidazole salt product of Ro 9-3559. The DE 2531031 of Wiegand and the FR 1519132 of BASF describe N-fluorenimidazole salts. The n-octyl or n-decyl R (Wiegand) and the C12-C | 6-alkyl r3 (basf) are the same as The Q group in the invention is different. -4-This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) ii Order ί / Μ (Read the notes on the back of the poem before filling this page) 415947 .... A 861 丨 7223 Please ask for a case 丨 > 7 Double_Chinese explanation tower 12 ^ B7 in 88 years, supplementary ancient five, invention description (Silas υ S 4, 2 6 7, 丨 7 9 summarizes the 呤 _ 4 types of organisms, which (please read the precautions on the back before filling out this page) Ar is: the formula of phenyl and the ㈣ substituent is 丨 · methylpropyl (3rd excerpt, lines 47 to 48)） 5_oxytriyl_4_repeated (3rd row, 5th row). These spit derivatives are in accordance with the examples of the present invention * JI, 2, J (R 〇 9-3577, R 〇 9-3631 And k0-3588) 's kj differs from the good' fluorenyltriazole salt product in that it does not have a substituted benzyl · N + N, X shao. It is similar to Naito and Hills' Mijun and Sanjun Compared with the derivatives, the N-demethylimidazole salt and N-deyltriazole salt of the present invention have superior water solubility and are very suitable for transdermal absorption. Compared with the imidazole salts of Jason Wiegand and BASF, The spit salt of the present invention is similar to The structure is significantly different. The present invention relates to a novel water-soluble azole compound that can be used to treat systemic mycosis and is suitable for oral and especially parenteral administration. Its manufacturing method contains their antifungal composition and treatment of mold More specifically, the present invention relates to the novel consumer formulas of the Central Samples Bureau of the Ministry of Economics and the Consumer Cooperatives of the Ministry of Economics.

Q為式II唑化合物之其餘部份 (I) 4a - 本纸汝尺度適用中國國家標準（CNS ) Α4規格（2丨0Χ297公釐） 415947 .... A 861丨7223跳I利巾請案 丨>7 双 _中文說明耸脩正阶88年12 i B7 ,，補古 五、發明説明（ 希啦斯之υ S 4，2 6 7，丨7 9概括地敘述了呤 _ 4類何生物，其 (請先Μ讀背面之注意事項再填寫本頁) 中Ar為：函苯基且㈣取代基為丨·甲丙基（第3摘， 47至48行）之式⑴之5_氧基三也基_4_屢（第3攔，第5 行）。這些吐類衍生物與本發明實施例 * J I , 2 , J ( R 〇 9 - 3577，R〇 9-3631 以及 R〇 9-3588)之 kj 从好 '卞基***鹽產 物不同處在於其不具有一經取代之苄基· N + N ，X邵分。 與内藤及希爾斯之咪峻及三峻衍生物相較，本發明之N _ 爷基咪唑鹽以及N-爷基***鹽具有優越之水溶性，其極適 於經皮吸收。 與傑森·韋根及B A S F之咪唑鹽相較，本發明之咪吐鹽 則與其在結構上顯不相同。 本發明係關於可用以治療系統黴菌病且適於口服及特別 是非經腸投藥之新穎水溶性唑化合物，其製造方法，含有 彼等之抗真菌組合物及治療黴菌病之方法。 更特定言之，本發明係關於以通式⑴表示之新穎w全化合 物 經濟部中央樣準局員工消費合作社印衷 其中Q is the remainder of the compound of formula II azole (I) 4a-The standard of this paper applies to the Chinese National Standard (CNS) A4 specification (2 丨 0 × 297 mm) 415947 .... A 861 丨 7223丨 > 7 Double _ Chinese description of the revised version of 88 i 12 B7, supplement ancient five, the description of the invention (Silas υ S 4, 2 6 7, 丨 7 9 summarizes the _ 4 types of Ho Biology, (please read the precautions on the back, and then fill out this page). Ar is: phenyl group and ㈣ substituent is 丨 · methylpropyl (3rd excerpt, lines 47 to 48). The oxytriyl group is 4- (3rd row, 5th row). These spit derivatives are in accordance with the examples of the present invention * JI, 2, J (R 〇9-3577, R 009-3631 and R. 9-3588) kj differs from the good 'fluorenyltriazole salt product in that it does not have a substituted benzyl · N + N, X Shaofen. It is in phase with Mito and Sanjo derivatives of Naito and Hills. In comparison, the N-demethylimidazole salt and N-deyltriazole salt of the present invention have superior water solubility, which is very suitable for transdermal absorption. Compared with the imidazole salts of Jason Wigan and BASF, the present invention Mitosalt is not structurally significant The present invention relates to a novel water-soluble azole compound that can be used to treat systemic mycosis and is suitable for oral and especially parenteral administration, a method for producing the same, an antifungal composition containing them, and a method for treating mycosis. More specifically In other words, the present invention is about the novel consumer represented by the General Coordination Bureau of the Central Bureau of Standards of the Ministry of Economics, which is represented by the general formula 消费.

Q為式II唑化合物之其餘部份 (I) 4a - 本纸汝尺度適用中國國家標準（CNS ) Α4規格（2丨0Χ297公釐） 41594? 第86117223珑專利申請案 中文說明左修正頁(88年丨2月） 五、發明说明（If· (II) 其具有抗真菌活性； Z 為氮或甲川； FL1與R2 各獨立為氫原子或-0Y基困[其中Y為在生理 (請先W讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印策 -4b - 本紙悵尺度通用中國國家標準（CNS ) A4規格（2IOX297公釐） 41594? 第86117223珑專利申請案 中文說明左修正頁(88年丨2月） 五、發明说明（If· (II) 其具有抗真菌活性； Z 為氮或甲川； FL1與R2 各獨立為氫原子或-0Y基困[其中Y為在生理 (請先W讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印策 -4b - 本紙悵尺度通用中國國家標準（CNS ) A4規格（2IOX297公釐）Q is the remainder of the compound of formula II azole (I) 4a-This paper applies the Chinese National Standard (CNS) A4 specification (2 丨 0 × 297 mm) 41594? 86117223 Long patent application Chinese description left amendment page (88 Years in February) 5. Description of the invention (If · (II) has antifungal activity; Z is nitrogen or Jiachuan; FL1 and R2 are each independently hydrogen atom or -0Y group [where Y is in physiology (please first W (Please read the notes on the back and fill in this page again.) The Central Consumers Bureau of the Ministry of Economic Affairs, Employee Cooperatives Cooperative Instruction-4b-Standard Chinese National Standard (CNS) A4 Specification (2IOX297mm) 41594? Chinese Patent No. 86117223 Long Patent Application Left amendment page (88 丨 丨 February 88) 5. Description of the invention (If · (II) It has antifungal activity; Z is nitrogen or Jiachuan; FL1 and R2 are each independently hydrogen atom or -0Y group [where Y is in Physiology (Please read the precautions on the back before filling out this page) Staff Consumer Cooperatives Cooperative Policy -4b-Standard Chinese National Standard (CNS) A4 Specification (2IOX297 mm)

41594? 第86丨丨7223^:專利申請案 A7 屮文說明書修正頁(88年12月)_B7 五、發明説明（34) 實例28 >矣化（21;1,3{^)-丨-[~3-[~4-(4-底基私基）-»塞吐-2-基1-2-(2,4-二氣苯基）-2-羥基-丁基1-4-丨4-丨(異丙基胺基）乙醯氧基〗-3、5-二甲基芊基1-1H-Π,2,41***-4- 三氟醋酸鹽；41594? Section 86 丨 丨 7223 ^: Revised page of patent application A7 manuscript specification (December 88) _B7 V. Description of invention (34) Example 28 > Huahua (21; 1,3 {^)-丨- [~ 3- [~ 4- (4-Substrate private group)-»Setup-2-yl1-2- (2,4-difluorophenyl) -2-hydroxy-butyl1-4- 丨4- 丨 (isopropylamino) ethoxyloxy-3,5-dimethylfluorenyl 1-1H-Π, 2,41triazole-4-trifluoroacetate;

物理形式：非晶質粉末；FAB-MS : m/z671 (M-Br)+ ; lH-NMR (CD3OD) o 1.24(3H，d，J=6.9Hz)，1.41(6H，cU=6.6Hz)，2.22(6H，s)，3.32-3.53 4.30(lH,qjJ=7.3Hz), 4.50(2H,s); 4.66(lH,d,J=14.2Hz), 5.12(lH,d5J=14. 2Hz), 5.34(2H,s)3 6.73-6.78(lH,m), 6.98-7.06(lH,m), 7.15(2H,s), 7.20〜7.29(lH，m), 7.82(2H,d，J=8.6Hz), 8.1 l(lH,s), 8.18(2H，d，J=8.6Hz), 8.74(1 H，s)。 實例29 溴化卜R(2R,3R)-3-丨4-(4-氰基苯基V塞唑-2-基〗-2-(2,4-二氟苯基）-2-羥基丁基M-丨(2SV4-丨乙胺基）丙醯氧基1-3>二甲基苄基〗-1沁 「1,2,41三吐-4- 三氟醋酸鹽；. 物理形式：非晶質粉末；MALDI-TOF-MS : m/z671 (M-Br)+ ; 1 H-NMR (CD3 OD) 5 1.24(3H,d,J=7.3Hz), 1.38(3H,t,J=7.3Hz), I.83(3H,d,J^7.3Hz), 2.21(6H,s), 3.14-3.25(2H,m), 4.30(lH,q,J=7.3Hz), 4.63(lH,q,J=7.3Hz), 4.66(lH1d,J=14.2Hz), 5.12(lH,d,J=14.2Hz), 5.35(2H,s), 6. 74~6.80(lH,m), 6.98-7.07(lH,m), 7.16(2H,s), 7.21- 7.30(1^1X1), 7.82(2H,d,J=8.6Hz), 8.11(lH,s), 8.18(2H,d,J=8.6Hz), 8.75(lH,s), 10.00( 1 H，s)。 f例30 溴化（2IURH-P-丨4-(4-氰基苯基）--塞唑-2-基1-2-(2,4-二氟苯基）-2- -37- 本紙張尺度適用中國國家標準（CNS ) A4規格（2丨0X297公釐） (請先閲讀背面之注意事項再填寫本頁)Physical form: amorphous powder; FAB-MS: m / z671 (M-Br) +; lH-NMR (CD3OD) o 1.24 (3H, d, J = 6.9Hz), 1.41 (6H, cU = 6.6Hz) , 2.22 (6H, s), 3.32-3.53 4.30 (lH, qjJ = 7.3Hz), 4.50 (2H, s); 4.66 (lH, d, J = 14.2Hz), 5.12 (lH, d5J = 14. 2Hz) , 5.34 (2H, s) 3 6.73-6.78 (lH, m), 6.98-7.06 (lH, m), 7.15 (2H, s), 7.20 ~ 7.29 (lH, m), 7.82 (2H, d, J = 8.6Hz), 8.1 l (lH, s), 8.18 (2H, d, J = 8.6Hz), 8.74 (1 H, s). Example 29 Br (2R, 3R) -3- 丨 4- (4-cyanophenyl Vselazol-2-yl) -2- (2,4-difluorophenyl) -2-hydroxybutyl M- 丨 (2SV4- 丨 Ethylamino) propanyloxy 1-3 > dimethylbenzyl〗 -1, "1,2,41 Tritul-4-trifluoroacetate; Physical form: Non Crystalline powder; MALDI-TOF-MS: m / z671 (M-Br) +; 1 H-NMR (CD3 OD) 5 1.24 (3H, d, J = 7.3Hz), 1.38 (3H, t, J = 7.3 Hz), I.83 (3H, d, J ^ 7.3Hz), 2.21 (6H, s), 3.14-3.25 (2H, m), 4.30 (lH, q, J = 7.3Hz), 4.63 (lH, q , J = 7.3Hz), 4.66 (lH1d, J = 14.2Hz), 5.12 (lH, d, J = 14.2Hz), 5.35 (2H, s), 6. 74 ~ 6.80 (lH, m), 6.98-7.07 (lH, m), 7.16 (2H, s), 7.21- 7.30 (1 ^ 1X1), 7.82 (2H, d, J = 8.6Hz), 8.11 (lH, s), 8.18 (2H, d, J = 8.6 Hz), 8.75 (lH, s), 10.00 (1H, s). FExample 30 Brominated (2IURH-P- 丨 4- (4-cyanophenyl)-sepazol-2-yl 1-2 -(2,4-Difluorophenyl) -2- -37- This paper size applies to Chinese National Standard (CNS) A4 (2 丨 0X297 mm) (Please read the precautions on the back before filling this page)

11T 經濟部中央樣隼局員工消費合作社印製 415947 Λ7 B7 五、發明说明（ 2 學條件下易於水解之基團]; R3與R4各獨立爲氫或鹵原子、低碳烷基、低碳烷氧 基、低碳烷硫基、（低碳烷羰基）硫甲基、羧 基或甲氧羰基；及 χ- 爲藥學上可接受之陰離子， 以及通式（I)化合物之鹽、水合物或溶劑合物。 於上述式I唑化合物中，較佳爲具有式⑺者11T Printed by the Consumer Cooperative of the Central Bureau of Economic Affairs of the Ministry of Economic Affairs 415947 Λ7 B7 V. Description of the invention (groups that are easy to hydrolyze under 2 academic conditions); R3 and R4 are each independently hydrogen or halogen atom, lower alkyl, lower alkyl Oxy, lower alkylthio, (lower alkylcarbonyl) thiomethyl, carboxyl or methoxycarbonyl; and χ- is a pharmaceutically acceptable anion, and a salt, hydrate or solvent of a compound of general formula (I) Among the azole compounds of the above formula I, those having the formula (I) are preferred.

R^'-COO B3R ^ '-COO B3

‘Q X" 其中 R5 ^---*---T---氣------訂 /V (請先聞讀背面之注意事項再填寫本頁) 經濟部中央標準扃負工消費合作社印製 爲直鏈或分枝狀q -c5烷基、芳基、吡啶 基、四氫吡咯基或Α-ΝΉ-Β-(其中A爲氫原 子或直鏈或分枝狀q -C5烷基；B爲直鏈或 分枝狀CrC4次烷基、-CH2-CONH-CH2-或 -CH2CH2CH2-CH(NH2)-); 各獨JL爲氫或鹵原子或低碳燒氧基；及 Z、Q及χ-均如上文定義。 於上述式1與Γ之唑化合物中，特佳者爲其中 Q爲下式基團 R3 與 R4 5 本紙張尺度適财賴家料、（CNS)以規格（21()>;297公.楚 五、發明説明（3) Λ7 Β7'Q X " of which R5 ^ --- * --- T --- qi ------ order / V (please read the precautions on the back before filling out this page) Central Standard of the Ministry of Economy Cooperatives are printed as straight-chain or branched q-c5 alkyl, aryl, pyridyl, tetrahydropyrrolyl or A-N-B- (where A is a hydrogen atom or a straight-chain or branched q-C5 alkane B; a linear or branched CrC4 alkylene group, -CH2-CONH-CH2- or -CH2CH2CH2-CH (NH2)-); each JL is hydrogen or a halogen atom or a low-carbon alkoxy group; and Z , Q and χ- are as defined above. Among the azole compounds of the above formula 1 and Γ, particularly preferred is where Q is a group of the formula R3 and R4 5 The paper size is suitable for household materials, (CNS) according to the specification (21 ()> 297). Chu V. Description of Invention (3) Λ7 Β7

(Q1)， -CH z(Q1), -CH z

(〇Λ (請先閲讀背面之注意事項再填寫本頁) 其中 D爲低碳烷醯基或下式基團 °κ νίΤ 經濟部中央標準局員工消費合作杜印製 R7爲鹵原子；及 R8爲直鏈或分枝狀q -C4烷基。 於上文所定義之通式（I)中之個別基團，係更詳細地解釋 如下： 式Π唑化合物 w—Q (ΪΙ)(〇Λ (Please read the precautions on the back before filling out this page) where D is a low-carbon alkyl group or a group of the formula ° κ νίΤ R7 is a halogen atom; It is a straight-chain or branched q-C4 alkyl group. The individual groups in the general formula (I) as defined above are explained in more detail as follows: Formula IIazole compound w-Q (XI)

-6- 本紙張尺度適用中國國家標準（CNS ) Λ4規格（210X 297公釐） 41594¾ 經濟部中央標準局員工消费合作社印繁 Λ7 Β7五、發明説明（4 )之實例爲 dl-l-[2-(2,4-二氣苯基）-2-[(2,4-二氣苯基）甲氧基]乙基]-1Η-咪唑 ， dl-順式-1-乙醯基-4-[4-[2-(2,4-二氣苯基）-2-(咪唛-1-基甲基）-1，3· 二氧伍圜-4-基]甲氧基]苯基]六氫吡，井， 私2-[(1切-第二-丁基]-4-[4-[4-[4-[(211,43)-2-(2,4-二氣苯基）-2-(111-1，2,4-***-1-基甲基）-1,3-二氧伍圜-4-基]甲氧基]苯基]-1-六氫吡 啼基]苯基-3H-[1,2,4]***-3-酮， 2- [(lR,2R)-2-(2,4-二氟苯基 >2-羥基-1-甲基-3-(1Η-1，2,4-***-1-基） 丙基]-4-[4-(2,2,3,3-四氟基丙氧基）苯基]-3(2H,4H)-1,2,4-***酮， (+)-2-(2,4-二氟苯基）_3-甲基-1-(111-1，2,4-***小基）-3-(6-(111-1，2,4-***-1-基）嗒畊基-3-基硫基）丁 -2-醇， (2R)-2-(2,4·二氟苯基)-1-[3-[(Ε)-4-(2,2,3,3-四氟基丙氧基)-苯乙烯 基]-(1,2,4-***-1-基）-3-(1，2,4-***小基）】丙-2-醇， dl-異赤蘚式-2-(2,4-二氟苯基）-3-甲基-靖醯基-1~〇沁1，2,4-***-卜基）-丁-2-醇， (_)冬[4-[4-[4-[[5-(2,4-二氟苯基）-5-(1Η-1,2,4-***-1-基甲基）四氫 呋喃-3-基]甲氧基]苯基]六氫吡畊基]苯基]-2-[(lS，2S)-l-乙基-2-羥丙基]-3H-1,2,4-***-3-酮， (2R，3R)-3-[4-(4-氰基苯基）〇塞唑-2-基）]-2-(2,4-二氟苯基）-1-(1Η-1，2,4-***-1-基）-丁-2-醇， 3- 甲基-3-甲硫基-1_(1，2,4-三竣-1-基）-2-(三氟甲基笨基）-丁 -2-醇 1-[[(111,28,611)-2-甲氧基-3,3-二甲基-6-(2-對-甲苯基乙基）環己 —_*____ · 7 -_____________— 本紙張尺度適用中國國家標準（CNS > Λ4規格（210XM7公釐） (請先閏讀背面之注意事項再填寫本頁) 415947 A7 ___________B7 五、發明説明（5 ) 基]-甲基]·1Η-[1,2,4]三峻， (5R，6R)-2,2c 甲基-6-[(出-1，2,4-***-1·基）甲基]-5_[[4-(三氟甲氧 基）苯氧基]甲基]環己酮0-甲基肟， 及其類似物。-6- This paper size applies the Chinese National Standard (CNS) Λ4 specification (210X 297 mm) 41594¾ Employee Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economy Yin Fan Λ7 Β7 V. The example of the invention description (4) is dl-l- [2 -(2,4-Diaminophenyl) -2-[(2,4-Diaminophenyl) methoxy] ethyl] -1H-imidazole, dl-cis-1-Ethyl-4- [4- [2- (2,4-Difluorophenyl) -2- (imidino-1-ylmethyl) -1,3 · dioxo-4-yl] methoxy] phenyl] Hexahydropyridine, well, private 2-[(1-cut-second-butyl] -4- [4- [4- [4-[(211,43) -2- (2,4-difluorophenyl ) -2- (111-1,2,4-triazol-1-ylmethyl) -1,3-dioxo-4-yl] methoxy] phenyl] -1-hexahydropyridine Phenyl] phenyl-3H- [1,2,4] triazol-3-one, 2-[(lR, 2R) -2- (2,4-difluorophenyl > 2-hydroxy-1-methyl Propyl-3- (1Η-1,2,4-triazol-1-yl) propyl] -4- [4- (2,2,3,3-tetrafluoropropoxy) phenyl] -3 (2H, 4H) -1,2,4-triazolone, (+)-2- (2,4-difluorophenyl) _3-methyl-1- (111-1,2,4-triazole Small group) -3- (6- (111-1,2,4-triazol-1-yl) dalophenyl-3-ylthio) but-2-ol, (2R) -2- (2, 4 · Difluorophenyl) -1- [3-[(E) -4- (2,2,3,3-tetrafluoropropoxy) -styryl]-(1, 2,4-triazol-1-yl) -3- (1,2,4-triazole small group)] propan-2-ol, dl-isoerythro-2--2- (2,4-difluorobenzene Yl) -3-methyl-Aristoloyl-1 ~ 〇qin 1,2,4-triazole-butyl) -but-2-ol, (_) dong [4- [4- [4-[[ 5- (2,4-difluorophenyl) -5- (1Η-1,2,4-triazol-1-ylmethyl) tetrahydrofuran-3-yl] methoxy] phenyl] hexahydropyracine Phenyl] phenyl] -2-[(lS, 2S) -1-l-ethyl-2-hydroxypropyl] -3H-1,2,4-triazol-3-one, (2R, 3R) -3- [4- (4-cyanophenyl) oxazol-2-yl)]-2- (2,4-difluorophenyl) -1- (1Η-1,2,4-triazole-1- ) -But-2-ol, 3-methyl-3-methylthio-l- (1,2,4-triend-1-yl) -2- (trifluoromethylbenzyl) -but-2 -Alcohol 1-[[(111,28,611) -2-methoxy-3,3-dimethyl-6- (2-p-tolylethyl) cyclohexyl —_ * ____ · 7 -_____________ — Paper size applies to Chinese national standard (CNS > Λ4 size (210XM7mm) (Please read the precautions on the back before filling out this page) 415947 A7 ___________B7 V. Description of the invention (5) Base] -methyl] · 1Η- [1,2,4] Sanjun, (5R, 6R) -2,2c methyl-6-[(Ex-1,2,4-triazole-1 · yl) methyl] -5 _ [[4- (Trifluoromethoxy) phenoxy] methyl] ring O-methyl ketone oxime, and the like.

Rl與R2各獨立爲氫原子或_〇γ基團[其中γ爲在生理學條 件下易於水解之基團]。 於上文中，在生理學條件下易於水解之Y基團，係意謂 較佳爲胺基酸之醯基殘基，或以下式表示之基團 R5C0-4(R60)2P0- 其中R5爲氫、低碳烷氡基、低碳烷基，其可視情況被 幾基、胺基、低破坑胺基、二低破坑胺基或芳基取代 ;及妒爲氫或低碳烷基。 當於本專利説明書中使用時，"低碳烷基"一詞係指較佳 爲具有1至4個碳原子之直鏈或分枝鏈，譬如甲基、乙基、 正-丙基、異丙基、丁基、異-丁基或第三-丁基。 "低碳烷氧基” 一詞係指較佳爲具有1至4個碳原子之直鏈 或分枝鏈，譬如甲氧基、乙氧基、正·丙氧基、異-丙氧基 、正-丁氧基、異-丁氧基。 經濟部中央標準局員工消費合作杜印製 I Hi !-— I I 11 -I - 1 抑衣 ---- I- I 1= I I — '1T (請先閲讀背面之注意事項再填寫本頁) ”芳基，，一詞係意謂較佳爲未經取代或經取代之芳基，譬 如苯基、甲氧苯基、吡啶基、吡畊基或呋喃基。 Y較佳爲甲酿基、乙酿基、丙酿基、異丁酿基、三甲基 乙酿基、破泊睡基、苯甲酿基、於給酿基、鱗酿基、二甲 基磷醯基、胺基乙醯基、3·胺基两酷基、4·胺基丁酿基、 (2-胺基乙醯胺基）_乙醯基、⑻_2,5_二胺基戊醯基、⑸冬胺 ______z8_z_ 本紙張尺度遶用中國國家樣隼（CNS ) A4規格（210X297公釐} 經濟部中央標準局貝工消費合作社印黎 415947 A7 ' __ B7____ 五、發明説明（6 ) 基丙醯基、（S)-四氫吡咯-2-羰基、（甲胺基）乙醯基、（丙胺 基）乙醯基、（S)-2-(甲胺基）丙醯基、3-(甲胺基）丙醯基、（S)-2-胺基-3-甲基丁醯基、（異丙胺基）乙醯基、（2S)-2-(乙胺基） 丙醯基、（乙胺基）乙醢基及其類似物。 R3與R4各獨立爲氫或鹵原子、低碳烷基、低碳烷氧基、 低碳烷硫基、（低碳烷羰基）硫甲基、羧基或曱氧羰基。 "鹵素"一詞表示氟、氣或溴。 ”低碳烷硫基"一詞係指較佳爲具有1至4個碳原予之直鏈 或分枝鏈，譬如甲硫基、乙硫基、正-丙硫基。 "低碳烷基"與"低碳烷氧基"術語，均與上述相同。 R3與R4較佳係獨立爲甲基、甲氧基或氣。 X·爲來自藥學上可接受之無機酸（例如礦酸）之陰離子， 譬如氣根、溴根或硫酸根；或來自有機酸，例如脂族、芳 族或芳脂族羧酸或磺酸之陰離子，譬如乙醯氧基、三氟乙 醯氧基、甲磺醯氧基陰離子及其類似物。 根據本發明之特佳化合物爲： 溴化dl-l-(4-乙醯氧基-3,5-二甲基芊基）-3-[2-(2,4-二氯苄氧基）-2-(2,4-二氣苯基）乙基]-3H_咪唑-1-後， 溴化dl-l-(4-乙醯氧基-3-甲苄基）-3-[2-(2,4-二氣苄氧基）-2-(2,4-二 氣笨基 ）乙基]-3H-咪唑 -1-銳， 溴化dl-l-(4-乙醯氧基苄基）-3-[2-(2,4-二氣芊氧基）·2-(2,4-二氣 苯基）乙基]-3Η-咪唑-1-後， 溴化dl-l-(4-乙醯氧基芊基）·3-[(2Κ，48)·4-[4-(4-乙醯基六氫吡畊-1-基）苯氧基甲基]-2-(2,4-二氣苯基）-[1，3]-二氧陸圜_2_基甲基]- ^ — — — - — - . - 9 - _ 本紙乐尺度適用t國國家標隼（CNS規格（2)0X297^^7 ~ (請先閲讀背面之注意事項再填寫本頁} 415947 A7 B7 五、發明説明（7 ) 3H-味咬-1-疏， 溴化dl-l-(4-乙醯氧基-3,5-二甲基苄基）-3-[(2R,4S)-4-[4-(4-乙醯 基六氫吡畊-1-基）苯氧基甲基]-2-(2,4-二氣苯基)-[1,3]-二氧陸園 -2-基甲基]-3H-味吐-1·後， 溴化d!-l-(4-乙醯氧基-3-甲苄基）-3-[(2R，4S)~4-[4-(4-乙醯基六氫 吡呼-1-基）苯氡基甲基]-2-(2,4-二氣苯基）-[1,3]-二氧陸園-2-基甲 基]-3H-咪峻-1-巍， 溴化dl-l-(4-乙醯氧基-3-甲氧基芊基）-3-[(2R，4S>4-[4-(4-乙醯基 六氫吡啫-1-基）苯氧基甲基]-2-(2,4-二氣苯基)-[1，3]-二氧陸園-2-基甲基]-3H-咪唑-1-鐵， 溴化dl-3-[(2R，4S)-4-[4-(4-乙醯基六氫吡畊-1-基）苯氧基甲基]-2-(2,4-二氯苯基)-[1,3]-二氧陸圜-2-基甲基異丁醯基氧基-3,5-二甲基苄基）-3H-咪唑-1為， 溴化(11-34(21^48)4-14-(4-乙醯基六氫》比畊小基）苯氧基甲基]·2_ (2,4·二氣苯基）-[1，3]-二氧陸園-2-基甲基]-1-(4-三甲基乙酿基氧 基-3,5-二甲基苄基）-3H-咪唑-1-鐵， 經濟部令央標準局員工消費合作社印聚 (讀先閲讀背面之注意事項再填寫本頁) 溴化(11-3-[(2民48)-4-[4-(4-乙酿基六氩〇比畊小基）苯氧基甲基]-2-(2,4~二氣苯基)-[1，3]-二氧陸園-2-基甲基]-l-[4-(2,2-二甲基丙酷氧 基）芊基]-3H-咪唑-1-巍， 漠化dl~4~(4_苯甲酿氧基-3,5-二甲基罕基）小[4_[4-[4-[4-(1-(2-丁 基_5-氧基-I，5·二氫[I，2,4]三吐冬基）苯基]六氫咐_小基]苯氧基 甲基]-2-(2,4-二氣苯基）-[1，3]二氧伍園-2-基甲基]·ιη_[1,2,4]三峻-4-巍， 溴化dl-4-[4-(吡啶-3-羰基氧基）-3,5-二甲基芊基]小[4_[4_[4_[4_(1_ --- ----10- 本紙張尺度適用中國國家標準（CNS ) A4規格（2!〇κ297公釐） 415947 經濟部中央榡準局貝工消費合作社印裂 A7 , B7五、發明説明（8 ) (2-丁基-5-氧基-1，5-二氫[1,2,4]***-4-基）苯基]六氫吡哜-1-基]苯 氧基甲基]-2-(2,4-二氣苯基）·[1，3]二氧伍圜-2-基甲基]-1H-[1，2,4] 三啥-4-鐵， 溴化 dl-4-(4-乙醯氧基-3,5-二甲基苄基）-1-[4-[4-[4-[4-[1-(2-丁基-5-氧基-1,5-二氫[1,2,4]***-4-基）苯基]六氫吡畊-1-基]苯氧基曱 基]-2-(2,4-二氣苯基）-[1，3]二氧伍圜-2-基甲基]-1H-[1，2,4]***-4-鎳， 溴化 dl-4-(4-乙醯氧基-3·甲芊基）-1·[4-[4-[4-[4-[1-(2-丁基-5-氧基-1,5-二氫[1，2,4]***-4-基）苯基]六氫吡畊-1-基]苯氧基甲基]-2-(2/J-二氣苯基）-[1,3]二氧伍圜-2-基甲基]-1Η-[1,2,4]***-4-後， 溴化 dl-4-(4-乙醯氧基苄基）-HH4-[4-[4-[l-(2-丁基-5-氧基-1,5-二氫[1，2,4]***-4-基）苯基]六氫吡畊-1-基]苯氧基甲基]-2-(2,4-二氣苯基二氧伍圜-2-基甲基】-1Η-[1，2,4〗***·4·銳， 甲烷磺酸 dl-l-[4-(4-{4-[4-(l-第二-丁基-5-氧基-1,5-二氫[1，2,4]三 唑-4-基）苯基]-六氫吡畊小基}-苯氧基甲基）-2-(2,4-二氣-苯基）-[1，3]二氧伍圜-2-基甲基]-4-(4-己醯氧基-3,5-二甲芊基）-1Η-[1，2,4] 三吐-4-鐵， 溴化4-(4-乙醯氧基-3,5-二甲基苄基）-l-[(2R，3R)-2-(2,4-二氟苯 基）-2-羥基-3-{5-氧基-4-[4-(2,2,3,3-四氟基丙氧基）苯基]-4>二氫 [1，2,4]*** _1_基} 丁基]-ιη-[1，2,4]***， 溴化4-(4-乙醯氧基-3>二甲基芊基）-l-[(2R)-2-(2,4-二氟笨基）-2-羥基-3-甲基-3-(6-[1,2,4]***-1-基-嗒_基-3-基對胺苯磺醯基） 丁基]_1H-[1,2,4]***》4德， 溴化4-(4-乙醯氧基-3,5-二甲基苄基）小[(2R)-2-(2,4-二氟苯基）- _____=_LL=__ 本紙張尺度適用中國國家標準（CNS丨A4規格（210X297公釐） (讀先聞讀背面之注意事項再填一巧本頁) ττ 415947 A7 · ----__ 五、發明説明（9 ) 2-羥基-3-(3-{(Z)-2-[4-(2,2,3,3-四氟基丙氧基）苯基]乙烯基卜[1,2,4] ***-1-基）丙基]-1H-[1,2,4]***-4-鐵， 漠化4-(4-乙驢乱基-3,5-二甲基卞基）-1-[(2尺1311)-2-(2,4-二氣苯 基）-2-羥基-3-甲烷磺醯基丁基]-1Η-[1,2,4]***-4-鐵， >臭化4-(4-乙酿氧基-3,5-二甲基卞基）~1-[(211-順式）-2-(2,4-二氣 苯基）*4-[4-[4-[4-[l-[(lS，2S)-l-乙基-2-經丙基）-5-氧基-1，5-二氮"[1，2,4] ***-4-基]苯基]六氫吡11 并-1-基]苯氧基甲基]四氫呋喃-2-基甲 基 1-111-[1,2,4]***_4-鐵， 溴化4-(4-乙醯氡基-3-甲芊基）-1-[(211-順式）-2-(2,4-二氟苯基）-4, [4-[4-[4-[H(lS,2S)-l-乙基-2-羥丙基）-5_氧基-1,5-二氫[1，2,4]***-4-基]笨基]六览'>比B井-1-基]苯氧基甲基]四氫咬喃~2-基甲基]-1H-[1，2,4]***-4·錄L， 溴化4~(4-己酿氧基字基）-1-[(2^順式）-2-(2,4-二氟苯基）~4-[4-[4-[4-[l-[(lS，2S)-l-乙基-2-羥丙基）-5-氧基-1,5-二氩[1,2,4]***-4-基]苯 基]六氫吡畊-1-基]笨氧基甲基]四氫呋喃-2-基甲基]4H-[1，2,4] 三峻-4-鐵， 經濟部中央榡準局員工消費合作杜印繁 J 1^1 I- ! H I-'- I J^r 1 I tt - - I : tn •i' (請先閲讀背面之注意事項再填寫本頁) 澳化4-(4-乙酿氧基_3,5·二氣卞基）-l-[(2R-順式）-2-(2,4-二氣苯 基）_4-[4-[4_[4-[l-[(lS，2S)-l-乙基-2-¾ 两基）-5-氧基-1，5-二氫[1,2,4]二 吨_4-基]苯基]六氮p比味小基]苯氧基甲基]四氣咬喃-2-基甲基]· 1Η·[1，2,4]***-4-娘， 溪化4-(4-乙醯氧基-3-氣ΐ基）-l-[(2R-順式）-2-(2,4-二氟苯基）-4-[4-[4-[4-[l-[(lS，2S)-l-(乙基-2-羥丙基）]-5-氧基·1，5·二氫[1，2,4]***-4-基]苯基]六氫ρ井小基]苯氧基甲基]四氫吱喃：基甲基]-1Η· [1，2,4]***-4-巍’ 本紙張尺度適用中國國家梯準（CNS ) Α4規格（210Χ2?7公t > 415947 Λ7 R7 五、發明説明（1(5 ) (請先閲讀背面之注意事項再填寫本頁〕 溴化4-(4-乙醯氧基-3,5-二甲基芊基）-1_[(2良311)-2-(2,4-二氟苯 基)-2-幾基-3·[4-(4-氰基苯基）ρ塞吐基]丁基HH-[1，2,4]三也冬錢 ， 溴化4-(4-乙醯氧基-3-甲芊基>H(2R，3R)-2-(2,4-二氟苯基）-2-經 基-3-[4-(4-氰基苯基 >塞唑-2-基]丁基]-丨H-[l，2,4]***-4-鐵， 溴化4-(4-乙醯氧基芊基）小[(211，31〇-2-(2,4-二氟苯基）-2-羥基-3-[4-(4-氰基苯基）嘧唑-2-基]丁基]4]***-4-旒， 溴化4<4-乙醯氧基-3,5-二氣苄基）-1-[(2民311)-2-(2,4-二氟苯基）-2-羥基-3-[4-(4-氰基苯基）嘧唑_2_基]丁基]-1H-〖1，2,4]***-4-鐵， 溴化4-(4-乙醯氧基-3-氣苄基）-1-[(211，31〇-2-(2,4-二氟苯基）_2-羥 基-3-[4-(4-氰基苯基）〃塞唑-2-基]丁基]-1H-[1，2,4]***4也， 溴化（2R,3R)-4-(4-胺基乙醯氧基-2-叛基苄基)-1-[3-[4-(4-氰基-苯 基）-'1塞吐-2-基]-2-(2,4-二氣苯基）-2-經基丁基]-出-[1,2,4]三吐~4-巍 三氟醋酸鹽， 溴化l-[(2R,3R)-3-[4-(4-氰基苯基）-嘧唑-2-基]-2-(2,4-二氟苯基）-2-羥基丁基]-4-[(S)-3,5-二曱基-4-(四氫吡咯-2-羰基氡基）-_基]-1Η·[1,2,4]***-4-鐵三氟醋酸鹽， 輕濟部中央榡準局員工消费合作社印製 溴化（2R，3R)-4-(4-胺基乙醯氧基-3,5-二甲基苄基）-〗·[3_[4-(4-氰 基苯基）-嘧唑-2-基]-2-(2,4-二氟苯基）-2-羥基丁基]-1Η-[1,2,4]*** -4-鐵三氟醋酸鹽， 溴化（2R，3R)-4-[4-(3-胺基丙醯氧基）-3,5-二甲基芊基]小[4-[4-(4-氰基苯基）_嘧唑-2-基]-2-(2+二氟苯基）-2-經基-3-甲基丁基]-1H-[U，4]***-4-鎳三氟醋酸鹽， 溴化（2R，3R)-4-[4-(4-胺基-丁醯氧基)-3,5-二甲基芊基]小[4-[4-(4-.度適用中國國家標隼（CMS ) A4規格（2丨GX297公楚） 經濟部中央標準局負4消費合作社印裝 41594^ Λ7 f _________ B7 五、發明説明（11 ) 氰基苯基）-p塞峻-2-基]-2-(2,4-二氟苯基）-2-獲基-3-甲基丁基] [1，2,4]***~4炎三氟醋酸鹽， 溴化（2R,3R)-4-[4-[[2-(胺基乙醯基）胺基]乙醯氧基]_35_二甲基 午基]-l-[3-[4-(4-氰基笨基）-〃塞峻_2-基]-2-(2,4·-二氟苯基）_2·經基. 丁基]-1H-[1,2,4]***-4-鐵三氟醋酸鹽， 溴化l-[(2R,3R)-3-[4-(4-氰基苯基）-嘍唑-2-基]·2·(2,4_二氟苯基）_ 2-羥基丁基]-4-[4-[(S)-2,5-二胺基戍醯氧基]-3,5-二甲基-爷基]_1Η· [1，2,4]***-4-巍三氟醋酸鹽， 溴化4-[4-[(S)-2-胺基-丙醯氧基）-3,5-二甲基苄基]-i_[(2R，3R)_3_ [4-(4-氰基苯基）-，塞吐-2-基]-2-(2,4-二氟苯基）-2-幾基-丁基]-1Η· [U,4]***-4-鐵三氟醋酸鹽， 溴化H(2R,3R)-3-[4-(4-氰基苯基）-嘧唑-2-基]-2-(2,4-二氟苯基）-2-羥基丁基]-4-[3,5-二甲基-4-[(甲胺基）乙醯氧基]爷基]-1H-[1，2,4] ****4-後三氟醋酸鹽， 溴化（2R，m)-l-[3-[4-(4-氰基苯基)-嘧唑-2-基]-2-(2,4·二氟苯基）-2-羥基丁基]-4-[3,5-二甲基-4-[(丙基胺基）乙醢氧基]苄基]-1Η- [1.2.4] ***>44三氟醋酸鹽， 溴化l-[(2R，3R)-3-[4-(4-氰基苯基）-嘍唑-2-基]-2-(2,4_二氟苯基）-2_羥基丁基]-4-[4-[(8)-2-(甲胺基）两醯氧基]-3,5-二甲基-爷基]-出_ [1.2.4] ***斗讒三氟醋酸鹽， 溴化（2IUR)-l-[4-[4-(4-氰基苯基）-嘧唑-2-基]-2-(2,4-二氟苯基）-2-羥基-3-甲基-丁基]-4-[3,5-二甲基冰[3-(甲胺基）-丙醯氧基]ΐ 基]-1Η-[1,2,4]***-4-鐵三氟醋酸鹽， 溴化4-[4-[(&)-2-胺基-3-甲基-丁醯氧基]-3,5-二甲基芊基]小 * 14 -_________—- 本纸張尺度適用中國囤家標隼（CNS ) Α4規格（2!〇Χ297公楚） I I - - I -i— J- i U .*民 I 11 1 - - - n -I 丁 -言 ./i\ (請先閱讀背面之注意事項再填寫本頁) A7 415947 B7 _ 丨丨 II.· — ··> m 麵· ·ι ι ι··_· η·_· 五、發明説明（12 ) [(2尺，3幻-3-[4-(4-氰基苯基）-嘍唑-2-基]-2-(2,4-二氟苯基）-2-羥基丁 基]-1Η-[1,2,4]***·4-鐵三氟醋酸鹽， 溴化（2艮3R)-l-[3-[4-(4·氰基苯基）-嘧唑-2-基]-2-(2,4-二氟苯基）-2-輕基-丁基]-4-[4-[(異丙基胺基）乙醯氧基】-3t5-二甲基苄基）-1Η-[1，2,4]***-4-巍三氟醋酸鹽， 溴化卜[(2艮31〇-3-[4-(4-氰基苯基)-嘍唑·2·基]-2-(2,4-二氟苯基）-2-羥基丁基]斗[(2S)-4-[2-(乙胺基）丙醯氧基]-3,5-二甲基-节基]-1H-[1,2,4]***冰鐵三氟醋酸鹽， 溴化（2良3厌)-1-[3-[4-(4-氰基苯基）-嘍唑-2-基]-2-(2,4-二氟苯基）-2-羥基丁基]-4-[4-[(乙胺基）乙醯氧基]-3,5-二甲基苄基]-1Η-[1，2,4] ***-4-巍三氟醋酸鹽， 溴化4-(4-乙醯氧基-3,5-二甲基芊基）-1-[2-羥基-3-甲基-3-甲基 對胺苯磺醯基-2·(4-三氟甲基苯基）丁基]-1Η-[1,2,4]***_4_鐵， 溴化4-(4-乙醯氧基-3,5-二甲基芊基）-H[(lR,6R)-2-甲氧亞胺基 -3,3-二甲基-6-[(4-三氟甲氧基苯氧基）甲基]環己基]甲基 [1，2,4]三崚斗巍， 溴化4-(4-乙醯氧基-3,5-二甲基芊基）-H(lR，2S,6R)-2-甲氧基-3,3-二甲基-6-(2-對-甲苯基-乙基）環己基甲基ΗΗ-ί1，2,4]***4- 傲， 溴化U(2R，3R)-3-[4-(4-氰基-苯基)-塞唑-2-基]_2_(2,4-二氟-苯基）· 2-羥基-丁基]-4-(3,5-二甲基-4-甲胺基乙醯氧基4基WH-t1，2,4] ***-4-歲鹽酸鹽， 氣化l-(2R,3R)-3-[4-(4_氰基-苯基)-p塞唑_2-基】-2-(2,4-二氟-苯基）-2-羥基-丁基]-4-(3,5-二甲基-4-甲胺基乙醯氧基·字基ΜΗ-Π，2,4] ___- is -________ 本紙張尺度適用中國國家標準（CNS ) A4規格（210x297公釐） C請先聞讀背面之注意事項真填寫本頁) 裴 訂 經濟部中央標準局員工消费合作社印f 41594? at B7 五、發明説明（13) ***-4-後鹽酸鹽’及 溴化l-(2R，3R)-3-[4-(4-氰基-苯基）-喳唑·2_基]-2-(2,4-二氟笨基）-2-羥基-丁基]-4-(3,5-二甲基-4-甲胺基乙醯氧基-苄基）_1Η-[ι，2,4] ***-4-巍氫溴酸鹽。 以通式（I)表示之新穎唑化合物，以及其鹽、水合物或溶 劑合物，可以下述方式製成 A)藉由反應具有抗眞菌活性之通式（II)峻化合物 ^ N-Q (II) 與通式（m)化合物 (請先閱讀背面之注意事項再填寫本頁) 袈 R2R1 and R2 are each independently a hydrogen atom or a -0γ group [wherein γ is a group that is easily hydrolyzed under physiological conditions]. In the above, the Y group which is easily hydrolyzed under physiological conditions means that it is preferably a fluorenyl residue of an amino acid, or a group represented by the formula R5C0-4 (R60) 2P0- where R5 is hydrogen , A lower alkyl alkanoyl group, a lower alkyl group, which may be optionally substituted by several groups, amine groups, low pit amine groups, di-low pit amine groups or aryl groups; and jealous for hydrogen or lower alkyl groups. As used in this patent specification, the term " lower alkyl " refers to a straight or branched chain preferably having 1 to 4 carbon atoms, such as methyl, ethyl, n-propyl Group, isopropyl, butyl, iso-butyl or tertiary-butyl. " Lower alkoxy "means a straight or branched chain preferably having 1 to 4 carbon atoms, such as methoxy, ethoxy, n-propoxy, iso-propoxy , N-butoxy, iso-butoxy. Consumption cooperation between employees of the Central Bureau of Standards of the Ministry of Economic Affairs Du Hi printed I Hi! -— II 11 -I-1 Suppression of clothing ---- I- I 1 = II — '1T (Please read the notes on the back before filling out this page) "Aryl", the term means preferably unsubstituted or substituted aryl, such as phenyl, methoxyphenyl, pyridyl, pyrocene Or furyl. Y is preferably methyl alcohol, ethyl alcohol, acrylic acid, isobutyl alcohol, trimethyl ethyl alcohol, hydrazone, benzyl alcohol, ethyl alcohol, ethyl alcohol, ethyl alcohol Phosphonium, aminoethylammonium, 3 · aminoammonium, 4 · aminobutanyl, (2-aminoethylammonium amine) _ethylammonium, fluorenyl-2,5_diaminopentanyl Base, aspartame ______z8_z_ This paper uses China National Sample (CNS) A4 (210X297 mm) for this paper size. The Central Standards Bureau of the Ministry of Economy, Shellfish Consumer Cooperative, India, 415947 A7 '__ B7____ 5. Description of the invention (6) Propionyl, (S) -tetrahydropyrrole-2-carbonyl, (methylamino) ethylfluorenyl, (propylamino) ethylfluorenyl, (S) -2- (methylamino) propanyl, 3- (Methylamino) propanyl, (S) -2-amino-3-methylbutylfluorenyl, (isopropylamino) ethylfluorenyl, (2S) -2- (ethylamino) propanyl, (ethyl Amine) Ethyl and its analogs. R3 and R4 are each independently hydrogen or halogen atom, lower alkyl, lower alkoxy, lower alkylthio, (lower alkylcarbonyl) thiomethyl, carboxyl Or oxocarbonyl. The term " halogen " means fluorine, gas, or bromine. The term " refers to a straight or branched chain preferably having 1 to 4 carbon atoms, such as methylthio, ethylthio, n-propylthio. " Lower alkyl " and & quot The term "low-carbon alkoxy" is the same as above. Preferably, R3 and R4 are independently methyl, methoxy or gas. X · is an anion derived from a pharmaceutically acceptable inorganic acid (such as mineral acid) , Such as gas, bromide or sulfate; or anions derived from organic acids, such as aliphatic, aromatic or araliphatic carboxylic acids or sulfonic acids, such as acetoxy, trifluoroacetoxy, mesylate Oxyanions and their analogues. A particularly preferred compound according to the present invention is: dl-l- (4-ethenyloxy-3,5-dimethylfluorenyl) -3- [2- (2, 4-Dichlorobenzyloxy) -2- (2,4-difluorophenyl) ethyl] -3H_imidazole-1-, bromide dl-l- (4-ethylamidooxy-3-methyl) Benzyl) -3- [2- (2,4-Digas benzyloxy) -2- (2,4-Digas benzyl) ethyl] -3H-imidazol-1-bromo, dl-1 -(4-Ethyloxybenzyl) -3- [2- (2,4-difluorofluorenyloxy) · 2- (2,4-difluorophenyl) ethyl] -3fluorene-imidazole-1 -After that, bromide dl-l- (4-ethoxyfluorenyl) · 3-[(2K, 4 8) · 4- [4- (4-Ethylhexylpyridin-1-yl) phenoxymethyl] -2- (2,4-difluorophenyl)-[1,3] -di Oxyhydrazone_2_ylmethyl]-^ — — —-—-.-9-_ This paper scale is applicable to national standards of China (CNS specification (2) 0X297 ^^ 7 ~ (Please read the note on the back first) Please fill in this page again for the matters} 415947 A7 B7 V. Description of the invention (7) 3H-taste bite-1-sulphate, bromide dl-l- (4-ethoxymethyl-3,5-dimethylbenzyl)- 3-[(2R, 4S) -4- [4- (4-Ethylhexylpyridin-1-yl) phenoxymethyl] -2- (2,4-difluorophenyl)-[ After 1,3] -dioxolan-2-ylmethyl] -3H-mito-1 ·, bromide d! -L- (4-ethoxymethyl-3-methylbenzyl) -3- [(2R, 4S) ~ 4- [4- (4-Ethylhexylpyridin-1-yl) phenylfluorenylmethyl] -2- (2,4-difluorophenyl)-[1, 3] -Dioxolyl-2-ylmethyl] -3H-Mijun-1-Wei, bromide dl-l- (4-ethoxymethyl-3-methoxymethyl) -3- [ (2R, 4S > 4- [4- (4-Ethylhexahydropyridin-1-yl) phenoxymethyl] -2- (2,4-difluorophenyl)-[1,3] -Dioxolan-2-ylmethyl] -3H-imidazole-1-iron, bromide dl-3-[(2R, 4S) -4- [4- (4-acetamidohexahydropyridine- 1-yl) phenoxymethyl] -2- (2,4-dichlorophenyl)-[1,3] -di Lupin-2-ylmethylisobutylfluorenyloxy-3,5-dimethylbenzyl) -3H-imidazole-1 is, (11-34 (21 ^ 48) 4-14- (4-ethyl Fluorenylhexahydro "Biao Xiaoji) Phenoxymethyl] · 2_ (2,4 · Difluorophenyl)-[1,3] -Dioxolyl-2-ylmethyl] -1- ( 4-trimethylethyloxy-3,5-dimethylbenzyl) -3H-imidazole-1-iron, printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (read the precautions on the back before reading) (Fill in this page) Brominated (11-3-[(2Min 48) -4- [4- (4-Ethyl hexahydrogen oxonyl) phenoxymethyl] -2- (2,4 ~ Dioxophenyl)-[1,3] -dioxolan-2-ylmethyl] -1- [4- (2,2-dimethylpropoxy) fluorenyl] -3H-imidazole -1- Wei, desertification dl ~ 4 ~ (4-benzyloxy-3,5-dimethylhenyl) small [4_ [4- [4- [4- (1- (2-butyl _5-Oxy-I, 5 · dihydro [I, 2,4] triurethyl) phenyl] hexahydrogenated_small group] phenoxymethyl] -2- (2,4-digas Phenyl)-[1,3] dioxo-2-ylmethyl] · ιη_ [1,2,4] Sanjun-4-Wei, brominated dl-4- [4- (pyridine-3- Carbonyloxy) -3,5-dimethylfluorenyl] small [4_ [4_ [4_ [4_ [1_ --- ---- 10- This paper size applies to Chinese National Standard (CNS) A4 specifications (2! 〇 297 mm) 415947 Printed A7, B7 by the Shellfish Consumer Cooperative of the Central Bureau of Quasi-Ministry of the Ministry of Economic Affairs 5. Description of the invention (8) (2-butyl-5-oxy-1,5-dihydro [1,2,4 ] Triazol-4-yl) phenyl] hexahydropyridin-1-yl] phenoxymethyl] -2- (2,4-difluorophenyl) · [1,3] dioxolidine- 2-ylmethyl] -1H- [1,2,4] Tris-4-iron, bromide dl-4- (4-ethoxymethyl-3,5-dimethylbenzyl) -1- [4- [4- [4- [4- [1- (2-butyl-5-oxy-1,5-dihydro [1,2,4] triazol-4-yl) phenyl] hexa Pyridin-1-yl] phenoxyfluorenyl] -2- (2,4-difluorophenyl)-[1,3] dioxol-2-ylmethyl] -1H- [1, 2,4] triazole-4-nickel, dl-4- (4-ethoxymethyl-3 · methylfluorenyl) bromide-1 · [4- [4- [4- [4- [1- [ 2-butyl-5-oxy-1,5-dihydro [1,2,4] triazol-4-yl) phenyl] hexahydropyrine-1-yl] phenoxymethyl] -2 -(2 / J-Diphenyl)-[1,3] dioxo-2-ylmethyl] -1 甲基-[1,2,4] triazole-4-, brominated dl-4 -(4-Ethyloxybenzyl) -HH4- [4- [4- [l- (2-butyl-5-oxy-1,5-dihydro [1,2,4] triazole- 4-yl) phenyl] hexahydropyridine-1-yl] phenoxymethyl] -2- (2,4-difluorophenyldioxo-2-ylmethyl] -1Η- [1 , 2,4〗 Triazole · 4 ·, Methanesulfonic acid dl-l- [4- (4- {4- [4- (l-second-butyl-5-oxy-1,5-dihydro [1,2,4] triazole-4 -Yl) phenyl] -hexahydropyridine} -phenoxymethyl) -2- (2,4-digas-phenyl)-[1,3] dioxol-2-ylmethyl [] Yl] -4- (4-hexanefluorenyloxy-3,5-dimethylamino) -1fluorene- [1,2,4] trisene-4-iron, 4- (4-ethoxyfluorenyl bromide -3,5-dimethylbenzyl) -l-[(2R, 3R) -2- (2,4-difluorophenyl) -2-hydroxy-3- {5-oxy-4- [4 -(2,2,3,3-tetrafluoropropoxy) phenyl] -4 > dihydro [1,2,4] triazol_1-yl} butyl] -ιη- [1,2, 4] Triazole, 4- (4-Ethoxyfluorenyl-3 > dimethylfluorenyl) -l-[(2R) -2- (2,4-difluorobenzyl) -2-hydroxy- 3-methyl-3- (6- [1,2,4] triazol-1-yl-da-yl-3-yl-p-aminobenzenesulfonyl) butyl] _1H- [1,2,4] Triazole> 4 German, 4- (4-Ethyloxy-3,5-dimethylbenzyl) bromide [(2R) -2- (2,4-difluorophenyl)-_____ = _ LL = __ This paper size applies to Chinese national standards (CNS 丨 A4 size (210X297 mm) (read the notes on the back and then fill in this page) ττ 415947 A7 · ----__ 5. Description of the invention (9 ) 2-hydroxy-3- (3-{(Z) -2- [4- (2,2,3,3-tetrafluoropropoxy) benzene Phenyl] vinyl [1,2,4] triazol-1-yl) propyl] -1H- [1,2,4] triazol-4-iron, desertified 4- (4-ethylamyl) -3,5-dimethylfluorenyl) -1-[(2 feet 1311) -2- (2,4-difluorophenyl) -2-hydroxy-3-methanesulfonylbutyl] -1Η- [1,2,4] triazole-4-iron, > odorized 4- (4-ethylamino-3,5-dimethylfluorenyl) ~ 1-[(211-cis) -2 -(2,4-Diaminophenyl) * 4- [4- [4- [4- [l-[(lS, 2S) -l-ethyl-2-transpropyl) -5-oxy- 1,5-diaza " [1,2,4] triazol-4-yl] phenyl] hexahydropyridine 11--1-yl] phenoxymethyl] tetrahydrofuran-2-ylmethyl 1- 111- [1,2,4] triazole_4-iron, 4- (4-ethylfluorenyl-3-formamyl) bromide-1-[(211-cis) -2- (2, 4-difluorophenyl) -4, [4- [4- [4- [H (lS, 2S) -1-ethyl-2-hydroxypropyl) -5_oxy-1,5-dihydro [1,2,4] triazol-4-yl] benzyl] hexan '> B-B-1-yl] phenoxymethyl] tetrahydroanyl ~ 2-ylmethyl] -1H- [1,2,4] triazole-4 · L, brominated 4 ~ (4-hexyloxy) -1-[(2 ^ cis) -2- (2,4-difluorobenzene Group) ~ 4- [4- [4- [4- [l-[(lS, 2S) -1-ethyl-2-hydroxypropyl) -5-oxy-1,5-diargon [1, 2,4] triazol-4-yl] phenyl] hexahydropyrine-1-yl] benzyloxymethyl] tetrahydrofuran-2- Methylmethyl] 4H- [1,2,4] Sanjun-4-iron, employee consumption cooperation of the Central Bureau of Quasi-Associate of the Ministry of Economy Du Yinfan J 1 ^ 1 I-! H I -'- IJ ^ r 1 I tt --I: tn • i '(Please read the precautions on the back before filling in this page) Australis 4- (4-ethynyloxy_3,5 · dioxanyl) -l-[(2R- 顺Formula) -2- (2,4-Difluorophenyl) _4- [4- [4_ [4- [l-[(lS, 2S) -l-ethyl-2-¾diyl) -5-oxy -1,5-dihydro [1,2,4] di-ton-4-yl] phenyl] hexazolium p-smellyl] phenoxymethyl] tetrahydro-2-ylmethyl] · 1Η · [1,2,4] triazol-4-methane, brook 4- (4-ethoxyfluoren-3-yloxy) -l-[(2R-cis) -2- (2 , 4-difluorophenyl) -4- [4- [4- [4- [l-[(lS, 2S) -1- (ethyl-2-hydroxypropyl)]-5-oxy · 1 , 5 · Dihydro [1,2,4] triazol-4-yl] phenyl] hexahydroρwell small group] phenoxymethyl] tetrahydrocranyl: ylmethyl] -1Η · [1, 2,4] Triazole-4-Wei 'This paper size applies to China National Standard (CNS) Α4 specification (210 × 2? 7 male t > 415947 Λ7 R7 V. Description of the invention (1 (5) (Please read the back Note: Please fill in this page again] 4- (4-Ethyloxy-3,5-dimethylfluorenyl) bromide-1 _ [(2 良 311) -2- (2,4-difluorophenyl) -2- a few -3 · [4- (4-cyanophenyl) ρ-sedetyl] butylHH- [1,2,4] Sanyedongqian, 4- (4-Ethyloxy-3-methyl bromide) Fluorenyl > H (2R, 3R) -2- (2,4-difluorophenyl) -2-meryl-3- [4- (4-cyanophenyl > serazol-2-yl] Butyl]-丨 H- [l, 2,4] triazole-4-iron, 4- (4-ethoxyfluorenyl) bromide small [(211,31〇-2- (2,4- Difluorophenyl) -2-hydroxy-3- [4- (4-cyanophenyl) pyrazol-2-yl] butyl] 4] triazole-4-fluorene, 4 < 4-acetamidine Oxy-3,5-digas benzyl) -1-[(2min 311) -2- (2,4-difluorophenyl) -2-hydroxy-3- [4- (4-cyanobenzene Yl) pyrimazole_2-yl] butyl] -1H- [1,2,4] triazole-4-iron, 4- (4-ethoxymethyl-3-benzyl) bromide-1- [(211,31〇-2- (2,4-difluorophenyl) _2-hydroxy-3- [4- (4-cyanophenyl) oxazol-2-yl] butyl] -1H- [1,2,4] triazole 4 also brominated (2R, 3R) -4- (4-aminoethoxy-2-benzylbenzyl) -1- [3- [4- (4 -Cyano-phenyl)-'1sedul-2-yl] -2- (2,4-difluorophenyl) -2-merylbutyl] -ex- [1,2,4] triturate ~ 4-Weitrifluoroacetate, l-[(2R, 3R) -3- [4- (4-cyanophenyl) -pyrazol-2-yl] -2- (2,4-di Fluorophenyl) -2-hydroxybutyl] -4-[(S) -3,5-difluorenyl-4 -(Tetrahydropyrrole-2-carbonylfluorenyl) -_ yl] -1Η · [1,2,4] triazole-4-iron trifluoroacetate, bromine printed by the Consumers' Cooperative of the Central Provincial Bureau of the Ministry of Light Industry (2R, 3R) -4- (4-Aminoethoxy-3,5-dimethylbenzyl)-〗 · [3_ [4- (4-cyanophenyl) -pyrimazole-2 -Yl] -2- (2,4-difluorophenyl) -2-hydroxybutyl] -1Η- [1,2,4] triazole-4-iron trifluoroacetate, brominated (2R, 3R ) -4- [4- (3-Aminopropionyloxy) -3,5-dimethylfluorenyl] small [4- [4- (4-cyanophenyl) _pyrazol-2-yl ] -2- (2 + difluorophenyl) -2-meryl-3-methylbutyl] -1H- [U, 4] triazole-4-nickel trifluoroacetate, bromide (2R, 3R ) -4- [4- (4-Amino-butyryloxy) -3,5-dimethylfluorenyl] small [4- [4- (4-.degree Applicable to China National Standard (CMS) A4 Specifications (2 丨 GX297 Gongchu) Central Standards Bureau of the Ministry of Economic Affairs, 4 prints of consumer cooperatives 41594 ^ Λ7 f _________ B7 V. Description of the invention (11) Cyanophenyl) -p-sechon-2-yl] -2- ( 2,4-difluorophenyl) -2-acyl-3-methylbutyl] [1,2,4] triazole ~ 4intrifluoroacetate, brominated (2R, 3R) -4- [ 4-[[2- (Aminoethenyl) amino] ethenyloxy] -35-dimethylamyl] -1- [3- [4- (4-cyanobenzyl -〃 峻 Jun_2-yl] -2- (2,4 · -difluorophenyl) _2 · yl. Butyl] -1H- [1,2,4] triazole-4-iron trifluoroacetic acid Salt, l-[(2R, 3R) -3- [4- (4-cyanophenyl) -oxazol-2-yl] · 2 ((2,4-difluorophenyl) _ 2- Hydroxybutyl] -4- [4-[(S) -2,5-diaminomethyloxy] -3,5-dimethyl-methylyl] _1 基 · [1,2,4] triazole 4-Weitrifluoroacetate, 4- [4-[(S) -2-amino-propanyloxy) -3,5-dimethylbenzyl] -i _ [(2R, 3R) _3_ [4- (4-Cyanophenyl)-, Seth-2-yl] -2- (2,4-difluorophenyl) -2-Epi-butyl] -1Η [U, 4 ] Triazole-4-iron trifluoroacetate, H (2R, 3R) -3- [4- (4-cyanophenyl) -pyrimazol-2-yl] -2- (2,4- Difluorophenyl) -2-hydroxybutyl] -4- [3,5-dimethyl-4-[(methylamino) ethoxymethyl] methylene] -1H- [1,2,4] Triazole * 4-post-trifluoroacetate, (2R, m) -1- [3- [4- (4-cyanophenyl) -pyrazol-2-yl] -2- (2,4 · Difluorophenyl) -2-hydroxybutyl] -4- [3,5-dimethyl-4-[(propylamino) ethoxy] benzyl] -1Η- [1.2.4] Triazole> 44 trifluoroacetate, l-[(2R, 3R) -3- [4- (4-cyanophenyl) -oxazol-2-yl] -2- (2,4_ Difluorophenyl) -2-hydroxybutyl] -4- [4-[(8) -2- (Methylamino) dioxo] -3,5-dimethyl-methylene] -out_ [1.2.4] triazolium trifluoroacetate, (2IUR) -l- [4- [4- (4-cyanophenyl) -pyrazol-2-yl] -2- (2,4-difluorophenyl) -2-hydroxy-3-methyl-butyl] -4- [3 , 5-dimethylice [3- (methylamino) -propanyloxy] fluorenyl] -1fluorene- [1,2,4] triazole-4-iron trifluoroacetate, 4- [Br 4-[(&)-2-Amino-3-methyl-butyryloxy] -3,5-dimethylfluorenyl] Small * 14 -_________—- This paper size is applicable to Chinese household standard隼 （CNS） Α4 Specification （2! 〇 × 297 公 楚） II--I -i— J- i U. * 民 I 11 1---n -I 丁-言 ./i \ (Please read the Please fill in this page again) A7 415947 B7 _ 丨 丨 II. · — ·· > m face · · ι ι ι ·· _ · η · _ · V. Description of the invention (12) [(2 feet, 3 magic -3- [4- (4-cyanophenyl) -oxazol-2-yl] -2- (2,4-difluorophenyl) -2-hydroxybutyl] -1Η- [1,2, 4] triazole · 4-iron trifluoroacetate, (2 艮 3R) -1- [3- [4- (4 · cyanophenyl) -pyrimazol-2-yl] -2- (2 , 4-difluorophenyl) -2-lightyl-butyl] -4- [4-[(isopropylamino) ethenyloxy] -3t5-dimethylbenzyl) -1Η- [1 , 2,4] Triazole-4-trifluorotrifluoroacetate, [Br2 (31) -3- (4- (4-cyanophenyl) -oxazole · 2 · yl] -2- (2,4- Difluorophenyl) -2-hydroxybutyl] pyridine [(2S) -4- [2- (ethylamino) propanyloxy] -3,5-dimethyl-benzyl] -1H- [1 , 2,4] triazole citric acid trifluoroacetate, bromide (2 good 3 ani) -1- [3- [4- (4-cyanophenyl) -oxazol-2-yl] -2- (2,4-difluorophenyl) -2-hydroxybutyl] -4- [4-[(ethylamino) ethoxy] -3,5-dimethylbenzyl] -1]-[1 , 2,4] triazole-4-trifluorotrifluoroacetate, 4- (4-ethytoxy-3,5-dimethylfluorenyl) -1- [2-hydroxy-3-methyl -3-methyl-p-aminobenzenesulfonyl-2 · (4-trifluoromethylphenyl) butyl] -1Η- [1,2,4] triazole-4_iron, bromide 4- (4 -Ethoxy-3-, 5-dimethylfluorenyl) -H [(lR, 6R) -2-methoxyimino-3,3-dimethyl-6-[(4-trifluoromethyl Oxyphenoxy) methyl] cyclohexyl] methyl [1,2,4] trimethylpyridine, 4- (4-ethoxymethyl-3,5-dimethylfluorenyl) -H bromide (lR, 2S, 6R) -2-methoxy-3,3-dimethyl-6- (2-p-tolyl-ethyl) cyclohexylmethylfluorene-ί1,2,4] triazole 4 -Pride, bromide U (2R, 3R) -3- [4- (4-cyano-phenyl) -thiazolyl-2-yl] _2_ (2,4-difluoro-phenyl) · 2-Hydroxy-butyl] -4- (3,5-dimethyl-4-methylaminoethylacetoxy 4-yl WH-t1,2,4] triazole-4-year-old hydrochloride, gasification l- (2R, 3R) -3- [4- (4-cyano-phenyl) -p-secazole_2-yl] -2- (2,4-difluoro-phenyl) -2-hydroxy- Butyl] -4- (3,5-dimethyl-4-methylaminoethylethoxy group · Myl-II, 2,4] ___- is -________ This paper size applies Chinese National Standard (CNS) A4 specifications (210x297 mm) C Please read the notes on the back and fill in this page first.) Peiding printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs f 41594? At B7 V. Description of the invention (13) After triazole-4- Hydrochloride 'and l- (2R, 3R) -3- [4- (4-cyano-phenyl) -oxazole · 2-yl] -2- (2,4-difluorobenzyl) -2-Hydroxy-butyl] -4- (3,5-dimethyl-4-methylaminoethylethoxy-benzyl) _1Η- [ι, 2,4] triazole-4-pyridine Acid salt. A novel azole compound represented by the general formula (I), and a salt, hydrate or solvate thereof, can be prepared in the following manner. A) A compound of the general formula (II) having anti-pyrene activity by reaction ^ NQ ( II) Compounds with general formula (m) (Please read the notes on the back before filling this page) 袈 R2

，-B 經濟部中央標準局員工消费合作社印製 其中R1與R2各獨立爲氫原子或_〇γ基團[其中γ爲在生 理學條件下易於水解之基團];R3與R4各獨立爲氫或 鹵原子、低碳烷基、低碳烷氧基、低碳烷硫基、（低 碳烷羰基）硫甲基、羧基或甲氧羰基；及L爲脱離基： 或 Β)藉由反應如上文定義之通式（π)化合物與通式（瓜）化合物 ，其中R1或R2之一爲羥基，接著是所形成化合物與式 R5 COL或（R6〇)2P〇L之反應，其中R^CO爲Ν-保護之胺基酸之 醯基殘基，或R5爲氫、低碳烷氧基、低碳烷基，其可視情 -16- 本紙乐尺度適用中國國家標準（CNS ) A4規格（210X29?公緩〉 經濟部中央標準局員工消費合作社印袋 415947 Λ7 ^_ B7__ 五、發明説明（14 ) 況被羧基、胺基、具有或未具有保護基之低碳烷胺基、二 -低碳烷胺基或芳基取代；及R6爲氫或低碳烷基，及L爲脱 離基，譬如羥基、氯、溴、OCOR5、甲烷磺醯基、對·甲苯 磺醯基及其類似物。 通式（Π)化合物與通式（ΙΠ)化合物之反應，可在溶劑中進 行，譬如二氯甲燒、氣仿、苯、甲苯、乙腈、四氫吱喃、 二氧陸圜或二甲基甲醯胺，較佳爲氯仿、乙腈或二甲基甲 醯胺。 於上述芊基化反應中之反應時間，可在相對較寬廣範園 内改變。一般而言，此反應可在o°c與i〇o°c之間，較佳係 在0°C與50°C間之溫度下進行。 於方法B中，醯化作用或磷醯化作用可於縮合劑存在下 ，譬如1-(3-二甲胺基丙基）-3-乙基碳化二亞胺鹽酸鹽及其類 似物，使用自由態酸，或者於酸接受劑存在下，譬如三乙 胺、吡啶 '甲基吡啶 '二甲基吡啶、二甲胺基吡啶或鹼金 屬碳酸鹽，使用i化醯、酸酐類、混合酐類、烷氧羰基鹵 化物、二烷氧基氣化磷醯或氣化磷醯，藉熟諳此藝者已知 之方法進行。 存在於式1Π化合物之R5中之胺基，較佳係被適當胺基保 護基保護，如第三-丁氧基羰基。 若必要，可在反應後，藉熟諳此藝者已知之程序移除保 護基。 式（I)化合物可含有胺基酸酯取代基R1及/或R2，此等取 代基可形成酸加成鹽。"式I化合物鹽"一詞，係指此種酸 ---- -17-_____ 本紙張尺度適用中國國家標準（CNS ) A4規格（2丨0X297公f ) (請先鬩讀背面之注意事項再填寫本頁) 裝., -B Printed by the Consumer Cooperatives of the Central Standards Bureau, Ministry of Economic Affairs, where R1 and R2 are each independently a hydrogen atom or a _〇γ group [where γ is a group that is easily hydrolyzed under physiological conditions]; R3 and R4 are each independently Hydrogen or halogen atom, lower alkyl, lower alkoxy, lower alkylthio, (lower alkylcarbonyl) thiomethyl, carboxyl or methoxycarbonyl; and L is a leaving group: or B) by A compound of the general formula (π) and a compound of the general formula (melon) as defined above, wherein one of R1 or R2 is a hydroxyl group, followed by a reaction of the formed compound with the formula R5 COL or (R6〇) 2POL, where R ^ CO is the fluorenyl residue of N-protected amino acid, or R5 is hydrogen, low-carbon alkoxy, or low-carbon alkyl, depending on the circumstances. -16- The paper scale is applicable to China National Standard (CNS) A4 specifications. (210X29? Public Notice) Printed bags for employees' cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 415947 Λ7 ^ _ B7__ V. Description of the invention (14) In the case of carboxyl groups, amine groups, low-carbon alkylamine groups with or without protective groups, di- Lower alkylamine or aryl substitution; and R6 is hydrogen or lower alkyl, and L is a leaving group, such as hydroxyl, chlorine, bromine, OC OR5, methanesulfonyl, p-toluenesulfonyl and the like. The reaction of the compound of the general formula (Π) and the compound of the general formula (II) can be carried out in a solvent, such as dichloromethane, aerosol, benzene , Toluene, acetonitrile, tetrahydrofuran, dioxolane or dimethylformamide, preferably chloroform, acetonitrile or dimethylformamide. The reaction time in the above amidation reaction can be relatively Change in a wider range. Generally speaking, this reaction can be carried out between 0 ° C and 100 ° C, preferably at a temperature between 0 ° C and 50 ° C. In method B, tritiated The effect or phosphating can be in the presence of a condensing agent, such as 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and the like, using a free acid, or In the presence of an acid acceptor, such as triethylamine, pyridine'methylpyridine 'dimethylpyridine, dimethylaminopyridine, or an alkali metal carbonate, hydrazone, acid anhydrides, mixed anhydrides, and alkoxycarbonyl halides , Dialkoxy vaporized phosphine or vaporized phosphine, carried out by methods known to those skilled in the art. The amine present in R5 of the compound of formula 1Π It is preferably protected by a suitable amine protecting group, such as a third-butoxycarbonyl group. If necessary, the protecting group can be removed after the reaction by procedures known to those skilled in the art. The compound of formula (I) may contain an amine Ester substituents R1 and / or R2, these substituents can form acid addition salts. The term "salts of compounds of formula I" refers to such acids ---- -17 -_____ This paper standard applies China National Standard (CNS) A4 specification (2 丨 0X297 male f) (Please read the precautions on the back before filling this page).

1T 41594? A7 ___B7 五、發明説明（15 ) 加成鹽。此等鹽可衍生自藥學上可接受之酸，如在前文關 於符號X"所述者。鹽形成可在移除保護基時進行，或可特 別藉由本質上已知之程序進行。 水合作用可在製造方法之過程中達成，或可由於最切無 水產物之吸濕性質之結果，慢慢地發生。與藥學上可接受 之溶劑譬如乙醇之溶劑合物，可於例如結晶化作用期間獲 得。 以通式（I)表示之新穎唑化合物以及其水合物或溶劑合物 ’具有比以通式（Π)表示之已知抗眞菌唑化合物遠爲較高之 水溶解度（參閱表1)。 表1 111 ί Hr Hr J τι I m · HI . /t (請先閱讀背面之注意事項再填一馬本頁) 經濟部中央標準局貝工消费合作社印製 化合物 (實例編號） 溶解度 (毫克/毫升） 溶劑* 1 1.0 b 2 0.4 b 3 0.4 b 4 >2.0 a 5 >1.0 a 6 6.5 a 7 >1.0 a 8 14.0 a 9 >2.0 a 10 >2.0 a 11 6.0 a 12 5.0 a 13 0.5 b 31 80 a *溶劑a=蒸餾水，溶劑b = Mellvaine緩衝劑（ρΗ8·02) -—___-—----— "18- 本紙張尺度適用中國國家標隼（CNS ) Λ4規格（210X297公釐） 415947 A7 B7 五、發明説明（16) 此外，此等新穎唑化合物在水溶液中，於室溫下係爲化 學上安定的，超過三天，但在小老鼠、大老鼠、猴子或人 類血漿中會有效地轉化成式（Π)化合物。 新穎通式（I)唑化合物之代表例，在人類血漿中個別轉化 成嗣康咬（ketoconazole)與依康咬（itraconazole)，係示於表2中。 將式（I)化合物在10微克/毫升濃度下，於37°C下，以人類 血漿培養高達120分鐘》 表2· 新穎唑化合物在人類血漿中轉化成酮康唑（KCZ)與依 康唑（ICZ) (讀先閲讀背面之注意事項再填寫本頁) 實例编號 轉化半衰期 培養時間 所發現物質（％ ) (分鐘） (分鐘） 化合物I KCZ 9 <1 5 <5 89 11 <1 5 <5 100 4 8.4 20 19 74 10 3.5 10 <5 80 ICZ 1 53 60 47 28 π 經濟部中央標準局真工消费合作社印製 本發明化合物之活體内功效，係示於表3中。將雄性 Fisher大老鼠F344/DuCrj品系採用於實驗感染模式，譬如系統 念珠菌病、系統麴菌病及肺麴菌病模式。將免疫適格之4 週大之老鼠使用於系統念珠菌病或系統麴菌病上，其係在 以白假絲酵母分生孢子5 X 106 /老鼠或以煙曲霉分生孢予 6xl05/老鼠，經由尾靜脈感染後發生。或者，對肺麵菌 病模式而言，係在以2xl05/老鼠，以氣管内方式感染之 前，將老鼠以可體松醋酸鹽處理，進行免疫抑制。對系統 與肺麵菌病而言，處理係在第一天進行兩次，及在隨後4 本紙乐尺度適用中國國家揉C'NS ) A&格（210X 297公~" ' ~ 415947 A7 ______ B7 五、發明説明（17 ) 天每曰一次（1 b.i. + 4 q，d.)，而對系統念珠菌病老鼠而言，係 在感染後之0、4、24及48小時下處理（1 bi.d, + 2 q.d.)。有效 劑量50% (ED50)値係在感染後第14天測定。 表3 ____(微莫耳/公斤） 系統念珠菌病 肺麴菌病 系統麴菌病 —靜脈内 口服 靜脈内 口服 靜脈内 口服 實例16 3.5 <2.1 實例23 4.6 4.7 依康唑 n.t. ILt. 氟康吐 n.t. >2.91T 41594? A7 ___B7 5. Description of the invention (15) Addition salt. These salts may be derived from pharmaceutically acceptable acids, such as those previously described with reference to the symbol X ". Salt formation can be carried out when the protecting group is removed, or it can be carried out, in particular, by procedures known per se. Hydration can be achieved during the manufacturing process or can occur slowly as a result of the hygroscopic nature of the most cut anhydrous products. Solvates with pharmaceutically acceptable solvents such as ethanol can be obtained, for example, during crystallization. The novel azole compound represented by the general formula (I) and its hydrate or solvate 'have a much higher water solubility than the known anti-conazole compounds represented by the general formula (Π) (see Table 1). Table 1 111 ί Hr Hr J τι I m · HI. / T (Please read the precautions on the back before filling in this page) Compounds printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (example number) Solubility (mg / Ml) Solvent * 1 1.0 b 2 0.4 b 3 0.4 b 4 > 2.0 a 5 > 1.0 a 6 6.5 a 7 > 1.0 a 8 14.0 a 9 > 2.0 a 10 > 2.0 a 11 6.0 a 12 5.0 a 13 0.5 b 31 80 a * Solvent a = Distilled water, Solvent b = Mellvaine buffering agent (ρΗ8 · 02) -—___-—----— " 18- This paper size applies to China National Standard (CNS) Λ4 specifications (210X297 mm) 415947 A7 B7 V. Description of the invention (16) In addition, these novel azole compounds are chemically stable at room temperature for more than three days in aqueous solution, but in mice, rats, monkeys Or human plasma will effectively convert to the compound of formula (Π). Representative examples of the novel azole compounds of the general formula (I) are individually converted into ketoconazole and itraconazole in human plasma. Incubate compounds of formula (I) in human plasma at a concentration of 10 μg / ml at 37 ° C for up to 120 minutes " (ICZ) (Read the precautions on the back before filling this page) Example number Substances found in the half-life culture time (%) (minutes) (minutes) Compound I KCZ 9 < 1 5 < 5 89 11 < 1 5 < 5 100 4 8.4 20 19 74 10 3.5 10 < 5 80 ICZ 1 53 60 47 28 π The in vivo efficacy of the compound of the present invention printed by the Real Industrial Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs is shown in Table 3. . The male Fisher rat F344 / DuCrj strain was used in experimental infection modes, such as systemic candidiasis, systemic rickets, and pulmonary bacillosis. Use immunocompetent 4-week-old mice for systemic candidiasis or systemic rickets, which are based on Candida albicans conidia 5 X 106 / mouse or Aspergillus fumigatus conidia 6xl05 / mouse, Occurs after infection through the tail vein. Alternatively, in the case of pneumococcal disease, the mice are treated with cortisone acetate before being infected intratracheally at 2xl05 / mouse for immunosuppression. For the system and pneumococcal disease, the treatment is performed twice on the first day, and the following 4 paper scales are applicable to the Chinese country C'NS) A & grid (210X 297 male ~ " '~ 415947 A7 ______ B7 V. Description of the invention (17) once a day (1 bi + 4 q, d.), And for systemic candidiasis mice, treatment is performed at 0, 4, 24, and 48 hours after infection (1 bi.d, + 2 qd). Effective dose 50% (ED50) is determined on day 14 after infection. Table 3 ____ (micromolar / kg) Systemic candidiasis Pneumococcosis System Psoriasis-vein Internal Oral Intravenous Oral Intravenous Oral Example 16 3.5 < 2.1 Example 23 4.6 4.7 Econazole nt ILt. Fluconazole nt > 2.9

- J Hr I I- i -T I II - I » 1_ •Jfv (請先聞讀背面之注意事項再填离本頁) 因此’根據本發明，以通式（X)表示之水溶性唑抗眞菌劑 ’以及其鹽、永合物或溶劑合物，在老鼠極中，於極寬廣 範圍之口服與非經腸劑量下，係顯示有效抗眞菌活性以抵 抗各種眞菌感染，包括麴菌病，並可有效作爲抗眞菌劑。 本發明進一步關於含有通式①唑化合物以及其鹽'水合 物或溶劑合物之醫藥組合物。 煙濟部中央榡準局員工消費合作社印裝 式（I)唆化合物以及其鹽、水合物或溶劑合物，係爲極具 活性之抗眞菌劑。其在抵抗多種眞菌物種上均具有活性， 包括假絲酵母屬、新型隱球酵母、曲霉屬、髮癖菌屬、小 孢霉屬、Exophiala屬、皮炎芽生菌及莢膜组織孢漿菌。 因此，本發明化合物可用於動物以及人類之黴菌病之局 部與系統治療。例如，其可用於治療因特别是假絲酵母屬 、髮癖菌屬或小孢霉屬所造成之局部與黏膜眞菌感染。其 亦可用於治療因例如假絲酵母屬、新型隱球菌屬' 曲霉屬 、Paracoceidiodes屬、側胞屬、Exophiala屬、芽酵母屬或組織胞 —------ -20- 本紙張尺錢财® 規格（210X297.公釐) — -- 415947 Λ7 B7 經濟部中央標隼局員工消费合作社印製 五、發明説明（18) 漿菌屬所造成之系統眞菌感染° 對臨床用途而言，式（I)唑化合物以及其鹽、水合物或溶 劑合物，可單獨投藥，但通常是以對於特定用途及所要目 的，按適當方式調配之醫藥混合物投藥，其方式是將賦形 劑、黏合劑 '潤滑劑、崩解劑、塗層物質、乳化劑、懸浮 劑、溶劑、安定劑、吸收加強劑及/或油膏基料混合6此 互混物可用於口服、注射、直腸或局部投藥。 供口服投藥之醫藥配方，可爲顆粒、片劑、糖塗覆片劑 、勝囊、丸劑、懸浮液或乳化液。對非經腸注射而言，例 如以靜脈内方式、肌内方式或皮下方式，式（I)唑類可以無 菌水溶液形式使用，其可含有其他物質，例如鹽或葡萄糖 以使溶液具等張性。此唑類亦可以栓劑或子宮托形式投藥 ，或其可以洗劑、溶液、乳膏、油膏或撒粉局部塗敷。 當以一、二或更多劑量藉口服或非經腸途徑投藥時，式 (I)唑化合物之曰服劑量程度，係爲約0J至約5〇毫克/公斤 (在分隔之劑量中）。因此’此等化合物之片劑或膠囊可含 有約6毫克至約〇·5克之活性化合物供投藥。無論如何，實 際劑量可由醫師決定，且其可依特定病人之年齡、體重及 回應而改變。 此外，式（I)唑化合物以及其鹽 '水合物或溶劑合物，具 有抵抗多種植物病原眞菌之活性，包括例如稻瘟病菌、 瓜果腐霉 '鍵格孢屬及擬青霉。 因此，其可應用於農業與園藝目的上，較佳係以對特定 用途及所要目的，按適當方式調配之組合物形式，例如撒 -21 - Μ氏張尺度制巾關家鮮（CNS ) A4规格77〗0Χ 297ϋϊ~) (請先閱讀背面之注意事項再填寫本頁) 策. 訂 415947 Λ7 B7 五、發明説明（19 )-J Hr I I- i -TI II-I »1_ • Jfv (Please read the precautions on the back before filling out this page) Therefore, according to the present invention, the water-soluble azole is represented by the general formula (X). Bactericides' and their salts, permanent compounds, or solvates have shown effective anti-bacillus activity in mouse poles at a wide range of oral and parenteral doses to combat various fungal infections, including rickets , And can be effectively used as an antibacterial agent. The present invention further relates to a pharmaceutical composition containing an azole compound of the general formula ① and a salt thereof, a hydrate or a solvate. The compound of formula (I) and its salts, hydrates or solvates are printed by the Consumer Cooperatives of the Central Bureau of Quasi-Quality of the Ministry of Tobacco, and are highly active anti-bactericides. It is active against a variety of P. spp. Species, including Candida, Cryptococcus neoformans, Aspergillus, Hairy genus, Microspora, Exophiala, Dermatitis, and Plasmodium spores . Therefore, the compounds of the present invention are useful in the local and systemic treatment of mycosis in animals and humans. For example, it can be used to treat local and mucosal taenia infections caused by, in particular, Candida, Hydratia or Microspora. It can also be used to treat factors such as Candida, New Cryptococcus, Aspergillus, Paracoceidiodes, Pleurotus, Exophiala, Saccharomyces, or Histoplasma. Choi ® Specification (210X297.mm) —-415947 Λ7 B7 Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs. 5. Description of the invention (18) Systemic fungal infection caused by Plasmodium spp. For clinical use, The azole compound of formula (I) and its salt, hydrate or solvate can be administered alone, but it is usually administered as a pharmaceutical mixture formulated for a specific use and desired purpose in an appropriate manner by excipients, adhesives Agents' lubricants, disintegrants, coating materials, emulsifiers, suspending agents, solvents, stabilizers, absorption enhancers and / or ointment bases. 6 This blend can be used for oral, injection, rectal or topical administration. . Pharmaceutical formulations for oral administration can be granules, tablets, sugar-coated tablets, capsules, pills, suspensions or emulsions. For parenteral injection, for example, intravenously, intramuscularly, or subcutaneously, the azoles of formula (I) can be used in the form of a sterile aqueous solution, which may contain other substances, such as salt or glucose, to make the solution isotonic. . The azoles can also be administered in the form of suppositories or pessaries, or they can be topically applied in the form of lotions, solutions, creams, ointments or dusters. When administered orally or parenterally in one, two or more doses, the oral dose of the azole compound of formula (I) ranges from about 0J to about 50 mg / kg (in divided doses). Thus, a tablet or capsule of these compounds may contain from about 6 mg to about 0.5 g of the active compound for administration. In any case, the actual dose can be determined by the physician, and it can vary depending on the age, weight and response of a particular patient. In addition, the azole compound of formula (I) and its salt 'hydrate or solvate have activity against a variety of plant pathogens, including Pyricularia oryzae, Pythium cucurbitae', Pseudomonas sp., And Paecilomyces. Therefore, it can be used for agricultural and horticultural purposes, preferably in the form of a composition formulated for a specific use and desired purpose in an appropriate manner, such as sprinkled 21-Μ Zhang scale towels Guanjia Xian (CNS) A4 Specification 77〗 0Χ 297ϋϊ ~) (Please read the precautions on the back before filling this page) Policy. Order 415947 Λ7 B7 V. Description of the invention (19)

In -I . I I t - I- «I I I I 1^^--- I (請先閲讀背面之注意事項再填{-本頁) 粉或顆粒、種子敷料、水溶液、分散液或乳化液、浸液、 喷霧劑或氣溶膠。此種組合物可含有已知且爲農業及園藝 上可接受之習用載劑、稀釋劑或佐劑。可將具有除草或殺 昆蟲作用I其他化合物，或其他抗眞菌藥摻入此等組合物 中。此等化合物與組合物，可以多種方式施用，例如;將 其直接施用至植物之葉子、莖、樹枝、種子或根部，或施 用至土壤或其他生長培養基，且其不僅可用以根治疾病， 而且可以預防方式保護植物或種子免受侵襲。 下述實例係説明製備本發明化合物之較佳方法，其並非 意欲將本發明之範圍限制於其上。 實例1 漠化4-(4-乙臨氧基-3,5-二甲基苄基）-〗_丨4_(4_丨4-丨4-(1-(2-丁基）·5·氡 基二氫三吨-4-基）苯基1六氫峨ρ井-1-基丨苯氧基曱基）_ 2-(2,4-一_氣苯基）-丨1，3] —戰伍園-2-基甲基】-1Η-[1，2,4~|三吐~4-^之 製備 經濟部中央標隼局員工消費合作社印製 於1克溴化3,5-二甲基·4-羥基苄與CHC13 -CH3 CN (万3毫升）之 溶液中，添加400毫克依康唑，並在室溫下持續攪拌15小 時。在眞空中蒸發溶劑，並於環境溫度下將殘留物在醋酐 -吡啶（4/4毫升）中攪拌2小時。使混合物濃縮並在矽膠（200 A，溶劑：CH2Cl2/MeOH=10/l)上管柱層析，獲得溴化4-(4-乙 醯氧基-3,5-二甲基芊基）-1-[4-(4-{4-[4-(1-(2-丁基）-5-氧基-1，5-二氫 [1,2,4]***-4-基）苯基]六氫吡畊-1-基}苯氧基甲基>2-(2,4-二氣 苯基）-[1，3]二氧伍圜-2-基甲基]-111-[1，2,4]***-4-鐵（507毫克，93 。/〇，爲非晶質粉末）； _____=J2Z^-- 本紙张尺度適用中國國家搮隼（CNS ) A4規格（210 X297公f ) 經濟部中央榡準局舅工消費合作社印製 415947 A7 B7五、發明説明（20 ) FAB-MS ： m/z881 (M-Br)+ ； 1H-NMR (CDC13) ό 0.90(3H,t,J=7.3Hz), 1.39(3H，(U=6.9Hz)，1.69〜1.77(lH，m), 1.81~1.87(lH,m)，2.02(3H，s), 2·10(3Η， s)，2.32(3H，s)，3.22~3.29(2H,m)，3.31 〜3.38(lH，m)，3.66~3.74(lH，m)，3.85〜3.9 l(lH,m), 4.11-4.15(lH,m), 4.28-4.33(2H,m), 4.35^.45(lH,m)} 5.02(lH,d,J=l 4.2Hz), 5.03(lH,d,J=14.5Hz), 5.13(lH,d,J=14.5Hz), 5.54(lH,d,J=14.2Hz), 6.88 〜7.04(8H，m), 7.29(1 H,dd，J=2.0,7_3Hz)，7.45(lH,d，J=8.9)，7.47(lH，d，J=2.0), 7_6 2(lH，s)，7,68(lH,dJ=8.2)，8.02(lH,s), 11.5〜11.6(lH,brs)。 於下述實例2~8中之化合物，係根據類似實例1之方式獲 得。 實例2 溴化4-(4-(吡啶-3-羰基氧基）-3,5-二甲基苄基）-1·丨4-(4-{4-丨4-(1-(2-丁 基）-5-氧基-1,5-二氫丨1,2,4】***-4-基）苯基1六氫吡畊-1-基1苯氧 基甲基）-2-(2,4-二氣苯基）-丨1，3〗二氧伍園-2-基甲基1-111-丨1，2,41三 峻-4-巍； 物理形式：非晶質粉末；MALDI-TOF-MS : m/z 945 (M-Br)+ ; 1 H-NMR (CD3〇D) δ 0.88(3ΗΛί=7.6Ηζ), 1.36(3H,d,J=5.3Hz), 1.73(2Η^η), 2.16(6H,s), 3.30(8H,m), 3.63-4.44(6H,m), 5.18(2H,s), 5.48(2H,s), 6.84-8.56 (18H,m)，9.01(lH,s)。 實例3 溴化4-(4-苯甲醯氧基-3,5-二甲基芊基）-1-丨4-(4·彳4·丨4-(1-(2-丁基）-5-氡基-1,5-二氫丨1,2,41***-4-基）苯基〗六氫吡畊-1-基}苯氧基甲 基）-2-(2,4-二氣苯基）-【1，3〗二氧伍園-2-基甲基〗-1沁丨1么4〗***-4· 鐵 : 物理形式：非晶質粉末；FAB-MS : m/z 943 (M-Br)+ ; 1H-NMR _- 93 -___ 本紙張尺度適用中國國家標準（CNS ) Λ4規格（2IOX297公釐） (讀先閱讀背面之注意事項再填寫本頁) 装· 訂 415947 經濟部中央標率局員工消費合作社印製 Λ 7 ' Β7五、發明説明（21 ) (d6-DMS0) ^ 0.80(3H,t,J=7.3Hz), 1.29(3H,d,J=6.6Hz), 1.67(2H,m)s 2.11 (6H,s), 3.40(8H,brs), 3.77(2H,m), 3.95(2H,m), 4.12(lH,m), 4.40(lH,m), 5.08(2 H,s), 5.42(2H,s), 6.90(2H,brd), 7.11~7.80(14H,m), 8.17(2H,d,J=7.2Hz), 8.35(1 H,s), 9.40(lH，s), 10.4(lH,s)。 實例4 溴化1-(4-乙醯氧基-3,5-二甲基-苄基）-3-丨(2R*，4S*)-4-丨4-(4-乙醯基-六氤吡畊-1-基）-苯氧基甲基】·2-(2,4-二氣-苯基)-丨1,3〗二氧伍園-2-基甲基1-3Η-咪唑-1-巍； 物理形式：淡褐色油；FAB-MS : m/z 707 (M-Br)+ ; 1H-NMR (CDC13) 2.11(6H,s),2.14(3H,s),2.33(3H,s),3.07(4H,m),3.62(2H,m), 168(lH，d(i，J=4.6，10.2Hz)，3.77(2H，m), 3.89〜3.95(2H,m)，4.02(lH,dd，J=4.0，ll. 6Hz)，4_37(lH，m)，4.85(2H，s)，5.08(lH，d，J=14.2Hz)，5.48(lH，d，J=14.2Hz)，6.8 l(2H，d,J=8.9Hz)，6.91(2H,d,J=8.9Hz), 6.99(lH，s), 7_05(2H，s)，7.18(lH，s)，7.31( lH，dd，J=2,0,8.6Hz)，7.47(111，(1,>2.0112)，7.69(111，(1片8.6112), KK42(lH,s)。 實例S 溴化3-丨(2R*,4S*)-4-丨4-(4-乙醯基-六氫吡啼-1-基）-苯氡基甲基]-2-(2,4-二氣-苯基）-丨1，3丨二氡伍園-2-基甲基1-1-(4-異丁醯氧基-3,5-二 甲基-芊基）-3H-咪唑; 物理形式：透明薄膜；FAB-MS : m/z 735 (M-Br)+ ; 1H-NMR (CDCI3) d 1.34(6H,d,J=6.9Hz), 2.09(6H,s), 2.14(3H,s), 2.85 (1H, sept,J=6.9Hz), 3.06(4H,m), 3.61(lH,dd,J=4.9,5.2Hz), 3.67(lH,dd,J=4.〇,l〇. 6Hz), 3.97(1 H,dd,J=4.9,5.2Hz), 3.90(2H,m), 3.97(lH,dd,J=4.〇,l〇 6Hz), 4.35(1 Η,ιη), 4.83(2H,s), 5.15(lH,d,J=14.5Hz), 5.49(lH,d,J=14.5Hz), 6.80(2H,d,J=8.9 Hz), 6.91(2H,d,J=8.9Hz), 7.08(2H,s), 7.10(lH,d,J=2.0Hz), 7.19(lH,brs)t 7.30(1 ____—S4- 本紙張尺度適用中國國家標攀（CNTS ) A4規格（2丨〇:< 297公嫠） -----------幕-- /IV (請先閱讀背面之注意事項再填寫本頁) 訂 經濟部中央標準局負工消費合作社印製 415947 A7 ___ B7 五、發明説明（22 ) H，dd,J=2.0,8.3Hz), 7.46(lH，d，J=2.0Hz)，7.67(lH，d，J=8.3Hz)，10.32(lH，brs)。 實例6 溴化1-(4_乙醯氧基-3,5-二氣苄基}-3-[(2R*,4S*)-丨4-丨4-(4-乙醯基-六 氫吡畊_1_基笨氧基甲基1-2-(2,4-二氣-苯基）-丨1,3〗二氧伍園-2-基 甲基1-3H-咪唑-1-鐵； 物理形式：淡褐色油；FAB-MS : m/z 747 (M-Br)+ ; 1H-NMR (CDC13) S 2.14(3H,s), 2.39(3H,s), 3.07(4H,m), 3.62(3H,m), 3.78(2H,m), 3.89 (lH,m), 3.97(lH,m),4.1〇(lH,m), 4.39(lH,m), 4.75(1^(1,J=16.2Hz), 4.83(lH,d, J=16.2Hz)，5.11(lH，d，J=14.8Hz)，5.77(lH，d，J=14.8Hz), 6.79(2H，cU=9.1Hz)，6. 92(2H,cU=9.1Hz)，7.01(lH,s)，7.22(lH，s)，7.33(lH,dd，J=8.6,2.0Hz)，7.42(2H，s) ,7.48(lH,d，J=2.0Hz)，7.68(lH，d，J=8.6Hz)，10.52(liis)。 實例7 溴化出-1-(4-乙酿氧基-3,5-二甲基-爷基)-3-丨2-(2,4-二氣-节氧基)-2-(2,4-二氣-苯基）-乙基〗-3H-咪唑-1-鐵； 物理形式：非晶質粉末；？处-1^:111/2 593 (]^-81')+;111-NMR (CD3 OD) δ 2.15(6H,s), 2.35(3H,s), 4.41-4.58(4H,m), 5.22(lH,dd,J=3.5,7,8Hz), 5.32(2H,s), 7.16(2H,brs), 7.24-7.56(7H,m)s 7.66(1H, d，J=1.0Hz), 9.00(lH，brs)。 實例8 溴化4-(4-乙醯氧基-3.5-二甲基-爷基VI-丨(lR，2S,6R)-2-甲氧基-3七 二甲基_6·(2-對-甲苯基-乙基）-環己基甲基1-1H-丨1,2,4〗***-4-氣 物理形式：無 6&;ΜΑΙΕ>Ι-ΤΟΡ-Μ8:ιη/ζ518(Μ_ΒΓ)+;ΐίϊ-NMR(CDC13) 0.84(3H,s), 1.02(3H,s), 1.10-1.30(3H,m), ______-25-___ 本紙張尺度適用中國國家標準（CNS ) A4規格（210Χ25Γ公釐） H I —4 m n 11 i- 1 , n I— 1 n n n· ./1> (請先閲讀背面之注意事項再填寫本頁) 41594； 經濟部中夬梂準局貝工消費合作社印策 A7 B7五、發明説明（23 ) 1,37〜1.42(lH，m)，1.45~1.65(lH,m)，1.71(lH，m)，1.93(2H，m)，2.15(6H，s)，2.31( 3H,s), 2.34(3H,s), 2.51(lH,m), 2.71(lH?m), 2.83(lH,d,J=10.9Hz), 3.50(3H,s), 4.49(lH,d,J=18.9Hz), 4.60(1 H,dd,J=l8.9,5.9Hz), 5.58(lH,d,J=14.4Hz)5 5.66(1 H，(U=14.4Hz)，7‘08(4H，s)，7.21(2H,s)，8.31(lH，s), 11.64(lH，s)。 實例9 溴化1-(4-乙醯氧基苄基）-3-丨(2R*，4S*)-4-丨4-(4-乙醯基六氫吡畊-1-基）苯氧基甲基1-2-(2,4-二氣苯基）-丨1，31二氧伍圜-2-基甲基1-3沁 咪峻-1·^之製備 於28毫克溴化4-乙醯氧基苄與1.5毫升CHC13之溶液中，添 加30毫克酮康唑，並將混合物於室溫下攪拌16小時。在眞 空中蒸發溶劑。於矽膠（WakogelC-200 ， 溶劑 ： CH2 Cl2 /MeOH = 10/1)上管柱層析，獲得溴化K4-乙醯氧基苄 基)-3-[(2R*,4S*)-4-[4-(4-乙醯基六氫吡畊-1-基）苯氧基甲基]-2-(2,4-二氣苯基）-[1，3]二氧伍圜-2-基曱基]-3H-咪唑-1-巍（32毫克，76 %，爲無色油）；MALDI-TOF-MS : m/z 679 (M-Br)+ ; 1H-NMR (CDC13) ^ 2.14(3H,s)? 2.28(3H,s), 3.05(4Η,ηι), 3.60~3.89(8H,m), 4.33(lH3m), 4.80(2Hss), 5.37(1Η,^Ι=14.5Ηζ), 5.61(lH,d,J=14.5Hz), 6.78(2H,cU=9.1Hz), 6. 92(2H，dJ=9.1Hz)，7.03(2H，d，J=8.6Hz), 7.24〜7.63(7H，m), 10.1(lH，s)。 於下述實例10〜13中之化合物’係根據類似實例9之方式獲得。 實例10 溴化3-丨(2R*，4S*V4-丨4-(4-乙醯基六氫吡畊-1-基）苯氧基甲基1-2-二氩苯基H1.31二氧伍圜-2·基甲基1-Η4-(2,2-二甲基丙醯氳 某、芊基1-3H-咪唑-1遽； -26- 本紙張尺度適用中國國家揉準（CNS ) A4現格（210X297公釐) "~~ (請先《讀背面之注意事項再填寫本頁) 經濟部中央標準局貝工消費合作社印製 41594? A7 ' B7五、發明説明（24 ) 物理形式：非晶質粉末；MALDI-TOF-MS : m/z 721 (M_Br)+ ; iH-NMR^CDCl〕）β 1.34(9H，s)，2，14(3H，s), 3‘06(4H，m)，3.60-4.00(8H，m), 4.36(lH,m), 4.81(2H,s), 5.29(lH,d,J=14.4Hz), 5.62(lH,d,J=14.4Hz), 6.80(2H,d, J=9.3Hz), 6.92(2H,d,J=9.3Hz), 7.02(2H,d,J=8.6Hz), 7.15(lH,brs)t 7.20(lH,brs), 7.28(lH,brs), 7.43(2H,d,J=8.6Hz), 7.46(lH,brs), 7.65(lH,d,J=8 3Hz), 10.3(1H, s) o 實例11 溴化1-(4-乙醯氧基-3-甲基-苄基）-3-丨(2R*.4S*)-4-丨4-(4-乙醯基-六 氫吡畊-1-基)-苯氧基甲基1-2-(2,4-二氣-苯基）-丨1.3〗二氧伍園-2-基 甲基1-3H-咪唑-1遽； 物理形式：透明薄膜；FAB-MS : m/z693 (M-Br)+ ; iH-NMR (CDC13)汐 2.13(6H，s)，2.31(3H，s)，3.06(4H，dt，J=5.0Hz)，3.62(2H，t,J=5.0Hz), 3.66(]H,dd，J=4.6Hz)，3.76(2H，t,J=9.0Hz)，3.88(2H,m)，3.94(lH，dd,J=4_6Hz)，4· 36(lH，m)，4.81(2H，s)，5.26(lH，d，J=R0Hz)，5.55(lH，d，J=14.0Hz)，6.79(2H，d，J =9.0Hz)f 6.91(2H,d,J=9.0Hz), 6.96(lHsd,J=8.0Hz), 7.22(2H,brs), 7.23(lH,dd,J =2.0,8.0Hz)，7.29(lH,dd,J=2.0,8.0Hz), 7.39(lH，brd), 7.45(lH，cU=2.0Hz)，7.64 (lH，dJ=8.0Hz), 10.21(lH，s)。 實例12 溴化1-(4-乙醯氣基-3-甲氧基-苄基）-3-丨(2R*,4S*V4-丨4-(4-乙醯基-六氫吡啡-1-基V笨氧基甲基1-2-(2,4-二氮•苯基MU1二氧伍圜-2- 基甲基卜3H-咪唑小後； 物理形式：非晶質粉末；MALDI-TOF-MS : m/z 709 (M-Br)+ ; 1H-NMR (CDC13) <ί 2.14(3H,s), 2.30(3H,s), 3.06(4H,m), 3.62(2H,m), 3.65(lH,dd,J=4.6,10.2Hz), 3.77(2H,m), 3.86(3H,s), 3.88-3.94(2H,m), f 本紙張尺度適用中國國家標準（CNS ) M規格（2丨0乂2_97公釐） (請先閱讀背面之注意事項再填寫本頁) 裝_ 、1Γ 經滴部中央標準局員工消費合作杜印策 41594? A7 ' B7五、發明説明（25 ) 4.03(lH，dd，J=4.0，l 1.6Hz)，4.36(lH，m)，4.80(2H，s)，5.12(lH,d，J=14.2Hz)，5.54( lH,d,J=14.2Hz), 6.80(2H,d,J=8.9Hz), 6.81(lH,s), 6.92(2H,d,J=8.9Hz), 6.96(1H, s), 7.07(lH，s)，7.17(lH，s), 7.31(lH，ddJ=2.0,8.6Hz)，7.44(1H，4J=2.0Hz)，7.47( lHje.OHz), 7.66(lH,d，J=8.6Hz)，10.41(lH，s)。 實例13 甲烷碏酸dl-1-丨4-(4-{4-丨4-(1-第二-丁基：氧基-1，5-二氫丨1,2,4〗***-4-基V苯基V六氫吡哜-1-基丨-笨氧基甲基)-2-(2,4-二氣-苯基）-丨1，3】 二氧伍園-2-基甲基>4-(4-己醯基氧基-3,5-二甲基-苄基）-1Η_ Γ1，2,4〗***-4-巍； 物理形式：非晶質粉末；卩灿-1^:111々937(1^純0)+;111-NMR(CDC13) 0.80-1.00(6H,m), 1.42(3H,d,J=6.6Hz), 1.20-1.50(6H,m), 1.70~2.00(2H,m), 2.10(9H,s), 2.58(2H,t,J=7.6Hz), 3.26(4H,m), 3.36(4H,m), 3.6 2~3.70(2H;m), 3.75(lH,m), 4.10~4.50(3H,m), 4.84(lH,d,J=14.2Hz), 5.00(lH,d, J=13,8Hz)，5.12(lH，d，J=13.8Hz)，5.44(lH,d，J=14.2Hz), 6.90(2H，<i，J=8,9Hz), 6. 94(2H,s), 6.99(2H,d,J=8.9Hz), 7.03(2H,d,J=8.9Hz), 7.3l(lH,dd,J=8.6,2.0Hz), 7. 43(2H,d,J=8.9Hz), 7.48(lH,d,J=2.0Hz), 7.62(lH;s), 7.71(lH,d,J=8.6Hz), 7.90( lH,s), 11.30(lH，s)。 實例U 溴化（2R，3R)-4-(4-乙醯基氧基-3,5-二甲基芊基）-1-丨3-丨4-(4-氰基苯 基）-嘍唑-2-基〗-2-(2,4-二氟苯基）-2-羥基-丁基〗-1Η-Π,2,41***-4-後 物理形式：非晶質粉末；FAB-MS : m/z 614 (M-Br)+ ; 1H-NMR (CD3OD) d 1.24(3H,cU=6.9Hz), 2.25(6H,s), 2.36(3H,s), 4.30(lH,q,J=6.9Hz), 4.64(lH,d,J=14.2Hz)s 5.10(lH,d,J=14.2Hz), 5.31(2H,s), 6.75-7.27(3Η?ιη), --—__-28-___ 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公嫠） (請先聞讀背面之注意事項再填寫本頁) ^15947 Λ7 ' ______B7_ 五、發明説明（26 ) 7.10(2H,s), 7.82(2H,d,J=8.3Hz), 8.09(lH,s), 8118(2H,d,J=8.2Hz)> 8.73(1H,s), 9. 95(lH,s)。In -I. II t-I- «IIII 1 ^^ --- I (Please read the precautions on the back before filling {-this page) Powder or granules, seed dressings, aqueous solutions, dispersions or emulsions, soaking solutions , Spray or aerosol. Such compositions may contain customary carriers, diluents or adjuvants which are known and are agriculturally and horticulturally acceptable. Other compounds having a herbicidal or insecticidal effect, or other antipyretics, can be incorporated into these compositions. These compounds and compositions can be applied in a variety of ways, for example; they can be applied directly to the leaves, stems, branches, seeds or roots of plants, or to soil or other growth media, and they can be used not only to cure diseases, but Preventive methods protect plants or seeds from attack. The following examples illustrate preferred methods for preparing the compounds of the invention and are not intended to limit the scope of the invention thereto. Example 1 Desertification 4- (4-Ethylphenoxy-3,5-dimethylbenzyl)-〗 _ 丨 4_ (4_ 丨 4- 丨 4- (1- (2-butyl) · 5 · Fluorenyldihydrotrityl-4-yl) phenyl 1 hexahydrofluorene-1-yl 丨 phenoxyfluorenyl) _ 2- (2,4-mono_phenylphenyl)-丨 1,3] —Zhanwuyuan-2-ylmethyl] -1Η- [1,2,4 ~ | Three vomiting ~ 4- ^ Prepared by the Ministry of Economic Affairs Central Standardization Bureau Staff Consumer Cooperatives Printed on 1 g of bromide 3,5- To a solution of dimethyl · 4-hydroxybenzyl and CHC13 -CH3 CN (3 ml), 400 mg of econazole was added, and stirring was continued at room temperature for 15 hours. The solvent was evaporated in the air, and the residue was stirred in acetic anhydride-pyridine (4/4 ml) at ambient temperature for 2 hours. The mixture was concentrated and subjected to column chromatography on silica gel (200 A, solvent: CH2Cl2 / MeOH = 10 / l) to obtain 4- (4-acetamidooxy-3,5-dimethylfluorenyl) bromide- 1- [4- (4- {4- [4- (1- (2-butyl) -5-oxy-1,5-dihydro [1,2,4] triazol-4-yl) benzene [Hexyl] hexahydropyridin-1-yl} phenoxymethyl > 2- (2,4-difluorophenyl)-[1,3] dioxol-2-ylmethyl] -111- [1,2,4] triazole-4-iron (507 mg, 93 ° / 〇, amorphous powder); _____ = J2Z ^-This paper size is applicable to China National Thorium (CNS) A4 specification (210 X297) f) Printed by the Central Consumers' Bureau of the Ministry of Economic Affairs, Industrial and Consumer Cooperatives 415947 A7 B7 V. Description of Invention (20) FAB-MS: m / z881 (M-Br) +; 1H-NMR (CDC13) 0.90 (3H , t, J = 7.3Hz), 1.39 (3H, (U = 6.9Hz), 1.69 ~ 1.77 (lH, m), 1.81 ~ 1.87 (lH, m), 2.02 (3H, s), 2.10 (3Η , S), 2.32 (3H, s), 3.22 ~ 3.29 (2H, m), 3.31 ~ 3.38 (lH, m), 3.66 ~ 3.74 (lH, m), 3.85 ~ 3.9 l (lH, m), 4.11- 4.15 (lH, m), 4.28-4.33 (2H, m), 4.35 ^ .45 (lH, m)} 5.02 (lH, d, J = l 4.2Hz), 5.03 (lH, d, J = 14.5Hz) , 5.13 (lH, d, J = 14.5Hz), 5.54 (lH, d, J = 14.2Hz), 6.88 to 7.04 (8H, m), 7.29 (1 H, dd, J = 2.0,7_3Hz), 7.45 (lH, d, J = 8.9), 7.47 (lH, d, J = 2.0), 7_6 2 (lH, s), 7,68 (lH, dJ = 8.2), 8.02 (lH, s), 11.5 to 11.6 (lH, brs). The compounds in the following Examples 2 to 8 were obtained in a similar manner to Example 1. Example 2 4- (4- (pyridine-3-carbonyloxy) bromide -3,5-dimethylbenzyl) -1 · 丨 4- (4- {4- 丨 4- (1- (2-butyl) -5-oxy-1,5-dihydro 丨 1, 2,4] triazol-4-yl) phenyl 1 hexahydropyridin-1-yl 1phenoxymethyl) -2- (2,4-dioxophenyl)-丨 1,3〗 dioxy Wuyuan-2-ylmethyl 1-111- 丨 1,2,41 Sanjun-4-Wei; Physical form: amorphous powder; MALDI-TOF-MS: m / z 945 (M-Br) +; 1 H-NMR (CD3〇D) δ 0.88 (3ΗΛί = 7.6Ηζ), 1.36 (3H, d, J = 5.3Hz), 1.73 (2Η ^ η), 2.16 (6H, s), 3.30 (8H, m) , 3.63-4.44 (6H, m), 5.18 (2H, s), 5.48 (2H, s), 6.84-8.56 (18H, m), 9.01 (lH, s). Example 3 4- (4-Benzylfluorenyloxy-3,5-dimethylfluorenyl) -1- 丨 4- (4 · 彳 4 · 丨 4- (1- (2-butyl)- 5-fluorenyl-1,5-dihydro 丨 1,2,41triazol-4-yl) phenyl] hexahydropyridin-1-yl} phenoxymethyl) -2- (2,4- Dioxophenyl)-[1,3] Dioxo-Wen-2-ylmethyl] -1 Qin 1 1 4 4 Triazole-4 · Iron: Physical form: amorphous powder; FAB-MS: m / z 943 (M-Br) +; 1H-NMR _- 93 -___ This paper size applies the Chinese National Standard (CNS) Λ4 specification (2IOX297 mm) (read the precautions on the back before filling this page) Order 415947 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Λ 7 'Β7 V. Description of the invention (21) (d6-DMS0) ^ 0.80 (3H, t, J = 7.3Hz), 1.29 (3H, d, J = 6.6Hz), 1.67 (2H, m) s 2.11 (6H, s), 3.40 (8H, brs), 3.77 (2H, m), 3.95 (2H, m), 4.12 (lH, m), 4.40 (lH, m), 5.08 (2 H, s), 5.42 (2H, s), 6.90 (2H, brd), 7.11 ~ 7.80 (14H, m), 8.17 (2H, d, J = 7.2Hz), 8.35 (1 H , s), 9.40 (lH, s), 10.4 (lH, s). Example 4 1- (4-Ethoxyfluorenyl-3,5-dimethyl-benzyl) -3- 丨 (2R *, 4S *)-4- 丨 4- (4-Ethylfluorenyl-hexa Pyridoxine-1-yl) -phenoxymethyl] · 2- (2,4-digas-phenyl)-丨 1,3〗 Dioxo-2-ylmethyl 1-3Η-imidazole -1- Wei; Physical form: light brown oil; FAB-MS: m / z 707 (M-Br) +; 1H-NMR (CDC13) 2.11 (6H, s), 2.14 (3H, s), 2.33 (3H , s), 3.07 (4H, m), 3.62 (2H, m), 168 (lH, d (i, J = 4.6, 10.2Hz), 3.77 (2H, m), 3.89 ~ 3.95 (2H, m), 4.02 (lH, dd, J = 4.0, ll. 6Hz), 4_37 (lH, m), 4.85 (2H, s), 5.08 (lH, d, J = 14.2Hz), 5.48 (lH, d, J = 14.2) Hz), 6.8 l (2H, d, J = 8.9Hz), 6.91 (2H, d, J = 8.9Hz), 6.99 (lH, s), 7_05 (2H, s), 7.18 (lH, s), 7.31 (lH, dd, J = 2, 0, 8.6 Hz), 7.47 (111, (1, > 2.0112), 7.69 (111, (1 piece 8.6112), KK42 (lH, s). Example S Bromide 3-丨 (2R *, 4S *)-4- 丨 4- (4-ethylfluorenyl-hexahydropyridin-1-yl) -phenylfluorenylmethyl] -2- (2,4-digas-phenyl )-丨 1,3 丨 Dioxin-2-ylmethyl 1- (4-isobutyridyloxy-3,5-dimethyl-fluorenyl) -3H-imidazole; Physical form: transparent Thin film; FAB-MS: m / z 735 (M-Br) +; 1H-NMR (CDCI3) d 1.34 (6H, d, J = 6 .9Hz), 2.09 (6H, s), 2.14 (3H, s), 2.85 (1H, sept, J = 6.9Hz), 3.06 (4H, m), 3.61 (lH, dd, J = 4.9,5.2Hz) , 3.67 (lH, dd, J = 4.0, 1.0 Hz), 3.97 (1 H, dd, J = 4.9, 5.2 Hz), 3.90 (2H, m), 3.97 (lH, dd, J = 4 .〇, 106 Hz), 4.35 (1 μ, ιη), 4.83 (2H, s), 5.15 (lH, d, J = 14.5Hz), 5.49 (lH, d, J = 14.5Hz), 6.80 (2H , d, J = 8.9 Hz), 6.91 (2H, d, J = 8.9Hz), 7.08 (2H, s), 7.10 (lH, d, J = 2.0Hz), 7.19 (lH, brs) t 7.30 (1 ____— S4- This paper size is applicable to China National Standards (CNTS) A4 specification (2 丨 〇: < 297 gong) ----------- curtain-/ IV (Please read the Please fill in this page for the matters needing attention) Order printed by the Central Bureau of Standards of the Ministry of Economic Affairs and Consumer Cooperatives to print 415947 A7 ___ B7 V. Invention Description (22) H, dd, J = 2.0, 8.3 Hz), 7.46 (lH, d, J = 2.0Hz), 7.67 (lH, d, J = 8.3Hz), 10.32 (lH, brs). Example 6 1- (4-Ethoxyfluorenyl-3,5-diaminobenzyl) -3-[(2R *, 4S *)-丨 4- 丨 4- (4-ethylfluorenyl-hexahydro Pycnyl_1-ylbenzyloxymethyl1-2- (2,4-digas-phenyl)-丨 1,3〗 Dioxo-2-ylmethyl 1-3H-imidazole-1- Iron; Physical form: light brown oil; FAB-MS: m / z 747 (M-Br) +; 1H-NMR (CDC13) S 2.14 (3H, s), 2.39 (3H, s), 3.07 (4H, m ), 3.62 (3H, m), 3.78 (2H, m), 3.89 (lH, m), 3.97 (lH, m), 4.1〇 (lH, m), 4.39 (lH, m), 4.75 (1 ^ ( 1, J = 16.2Hz), 4.83 (lH, d, J = 16.2Hz), 5.11 (lH, d, J = 14.8Hz), 5.77 (lH, d, J = 14.8Hz), 6.79 (2H, cU = 9.1Hz), 6.92 (2H, cU = 9.1Hz), 7.01 (lH, s), 7.22 (lH, s), 7.33 (lH, dd, J = 8.6, 2.0Hz), 7.42 (2H, s) , 7.48 (lH, d, J = 2.0 Hz), 7.68 (lH, d, J = 8.6 Hz), 10.52 (liis). Example 7 Bromination of 1- (4-ethoxyl-3,5- Dimethyl-fecyl) -3- 丨 2- (2,4-digas-benzyloxy) -2- (2,4-digas-phenyl) -ethyl〗 -3H-imidazole-1- Iron; Physical form: amorphous powder;? -1: 111/2 593 (] ^-81 ') +; 111-NMR (CD3 OD) δ 2.15 (6H, s), 2.35 (3H, s) , 4.41-4.58 (4H, m), 5.22 (lH, dd, J = 3.5,7,8Hz), 5.32 (2H, s), 7.16 (2H, brs), 7.24-7.56 (7H, m) s 7.66 ( 1H, d J = 1.0Hz), 9.00 (lH, brs). Example 8 4- (4-Ethoxyfluorenyl-3.5-dimethyl-methylyl) VI- 丨 (lR, 2S, 6R) -2-methoxy -Heptamethyl-6 · (2-p-tolyl-ethyl) -cyclohexylmethyl 1-1H- 丨 1,2,4〗 Triazole-4-Gas Physical Form: None 6 &; ΜΑΙΕ > 1-ΤΟΡ-Μ8: ιη / ζ518 (Μ_ΒΓ) +; ΐί-NMR (CDC13) 0.84 (3H, s), 1.02 (3H, s), 1.10-1.30 (3H, m), ______- 25 -___ This paper size applies Chinese National Standard (CNS) A4 specification (210 × 25Γmm) HI —4 mn 11 i- 1, n I— 1 nnn · ./1> (Please read the notes on the back before filling this page) 41594 ; Instruction A7 B7, Shellfish Consumer Cooperative of China ’s Central Bureau of Standards, Ministry of Economic Affairs 5. Description of the invention (23) 1,37 ~ 1.42 (lH, m), 1.45 ~ 1.65 (lH, m), 1.71 (lH, m), 1.93 (2H, m), 2.15 (6H, s), 2.31 (3H, s), 2.34 (3H, s), 2.51 (lH, m), 2.71 (lH? M), 2.83 (lH, d, J = 10.9Hz), 3.50 (3H, s), 4.49 (lH, d, J = 18.9Hz), 4.60 (1 H, dd, J = l8.9,5.9Hz), 5.58 (lH, d, J = 14.4Hz ) 5 5.66 (1 H, (U = 14.4 Hz), 7'08 (4H, s), 7.21 (2H, s), 8.31 (lH, s), 11.64 (lH, s). Example 9 1- (4-Ethyloxybenzyl) -3- 丨 (2R *, 4S *)-4- 丨 4- (4-Ethylhexahydropyridine-1-yl) phenoxy Methyl 1-2- (2,4-difluorophenyl)-丨 1,31 dioxol-2-ylmethyl 1-3 qinmijun-1 · ^ prepared in 28 mg bromide 4 -To a solution of ethoxybenzyl and 1.5 ml of CHC13, 30 mg of ketoconazole was added and the mixture was stirred at room temperature for 16 hours. The solvent was evaporated in the air. Column chromatography on silica gel (WakogelC-200, solvent: CH2Cl2 / MeOH = 10/1) to obtain K4-ethoxybenzyl bromide) -3-[(2R *, 4S *)-4- [4- (4-Ethylhexylpyridin-1-yl) phenoxymethyl] -2- (2,4-difluorophenyl)-[1,3] dioxolane-2- Methylmethyl] -3H-imidazol-1-yl (32 mg, 76%, colorless oil); MALDI-TOF-MS: m / z 679 (M-Br) +; 1H-NMR (CDC13) ^ 2.14 ( 3H, s)? 2.28 (3H, s), 3.05 (4Η, ηι), 3.60 ~ 3.89 (8H, m), 4.33 (lH3m), 4.80 (2Hss), 5.37 (1Η, ^ Ι = 14.5Ηζ), 5.61 (lH, d, J = 14.5Hz), 6.78 (2H, cU = 9.1Hz), 6.92 (2H, dJ = 9.1Hz), 7.03 (2H, d, J = 8.6Hz), 7.24 ~ 7.63 (7H , M), 10.1 (lH, s). The compounds' in the following Examples 10 to 13 were obtained in a manner similar to that of Example 9. Example 10 3- 丨 (2R *, 4S * V4- 丨 4- (4-Ethylhexyl-1-pyridyl-1-yl) phenoxymethyl1-2-diarginylphenyl H1.31 Oxygen-2 · ylmethyl 1-Η4- (2,2-dimethylpropanone, fluorenyl 1-3H-imidazole-1 遽; -26- This paper size applies to Chinese national standards (CNS ) A4 (210X297 mm) " ~~ (Please read the "Notes on the back side before filling out this page") Printed by the Central Standards Bureau of the Ministry of Economy, Shellfish Consumer Cooperative, 41594? A7 'B7 V. Invention Description (24) Physical form: amorphous powder; MALDI-TOF-MS: m / z 721 (M_Br) +; iH-NMR ^ CDCl]) β 1.34 (9H, s), 2,14 (3H, s), 3'06 (4H, m), 3.60-4.00 (8H, m), 4.36 (lH, m), 4.81 (2H, s), 5.29 (lH, d, J = 14.4Hz), 5.62 (lH, d, J = 14.4 Hz), 6.80 (2H, d, J = 9.3Hz), 6.92 (2H, d, J = 9.3Hz), 7.02 (2H, d, J = 8.6Hz), 7.15 (lH, brs) t 7.20 (lH, brs), 7.28 (lH, brs), 7.43 (2H, d, J = 8.6Hz), 7.46 (lH, brs), 7.65 (lH, d, J = 8 3Hz), 10.3 (1H, s) o Example 11 Bromide 1- (4-Ethyloxy-3-methyl-benzyl) -3- 丨 (2R * .4S *)-4- 丨 4- (4-Ethyl-hexahydropyroxy-1 -Yl) -phenoxymethyl 1- 2- (2,4-digas-phenyl)-丨 1.3〗 Dioxin-2-ylmethyl 1- 3H-imidazole-1 遽; Physical form: transparent film; FAB-MS: m / z693 (M-Br) +; iH-NMR (CDC13) Xi 2.13 (6H, s), 2.31 (3H, s), 3.06 ( 4H, dt, J = 5.0Hz), 3.62 (2H, t, J = 5.0Hz), 3.66 (] H, dd, J = 4.6Hz), 3.76 (2H, t, J = 9.0Hz), 3.88 (2H , m), 3.94 (lH, dd, J = 4_6Hz), 4.36 (lH, m), 4.81 (2H, s), 5.26 (lH, d, J = R0Hz), 5.55 (lH, d, J = 14.0Hz), 6.79 (2H, d, J = 9.0Hz) f 6.91 (2H, d, J = 9.0Hz), 6.96 (lHsd, J = 8.0Hz), 7.22 (2H, brs), 7.23 (lH, dd , J = 2.0, 8.0 Hz), 7.29 (lH, dd, J = 2.0, 8.0 Hz), 7.39 (lH, brd), 7.45 (lH, cU = 2.0 Hz), 7.64 (lH, dJ = 8.0 Hz), 10.21 (lH, s). Example 12 1- (4-Ethinofluorenyl-3-methoxy-benzyl) -3- 丨 (2R *, 4S * V4- 丨 4- (4-Ethylfluorenyl-hexahydropyridine- 1-yl-V-benzyloxymethyl 1- 2- (2,4-diaze • phenyl MU1 dioxo-2-ylmethyl 3H-imidazole small; physical form: amorphous powder; MALDI -TOF-MS: m / z 709 (M-Br) +; 1H-NMR (CDC13) < ί 2.14 (3H, s), 2.30 (3H, s), 3.06 (4H, m), 3.62 (2H, m), 3.65 (lH, dd, J = 4.6,10.2Hz), 3.77 (2H, m), 3.86 (3H, s), 3.88-3.94 (2H, m), f This paper size applies to the Chinese National Standard (CNS ) M specification (2 丨 0 乂 2_97mm) (Please read the precautions on the back before filling out this page) _ _ 1 1 The consumer cooperation of the Central Bureau of Standards of Didi Department Du Yince 41594? A7 'B7 V. Description of the invention (25) 4.03 (lH, dd, J = 4.0, l 1.6 Hz), 4.36 (lH, m), 4.80 (2H, s), 5.12 (lH, d, J = 14.2 Hz), 5.54 (lH, d, J = 14.2Hz), 6.80 (2H, d, J = 8.9Hz), 6.81 (lH, s), 6.92 (2H, d, J = 8.9Hz), 6.96 (1H, s), 7.07 (lH, s) , 7.17 (lH, s), 7.31 (lH, ddJ = 2.0,8.6Hz), 7.44 (1H, 4J = 2.0Hz), 7.47 (lHje.OHz), 7.66 (lH, d, J = 8.6Hz), 10.41 (lH, s). Example 13 Methanoic acid dl-1- 丨 4- (4- {4- 丨 4- (1-second- Group: oxy-1,5-dihydro 丨 1,2,4〗 triazol-4-yl Vphenyl V hexahydropyridin-1-yl 丨 -benzyloxymethyl) -2- (2, 4-Digas-phenyl)-丨 1,3] Dioxo-2-ylmethyl > 4- (4-hexylfluorenyloxy-3,5-dimethyl-benzyl) -1Η_ Γ1,2,4〗 Triazole-4-Wei; Physical form: amorphous powder; 卩 Can-1 ^: 111々937 (1 ^ pure 0) +; 111-NMR (CDC13) 0.80-1.00 (6H, m), 1.42 (3H, d, J = 6.6Hz), 1.20-1.50 (6H, m), 1.70 ~ 2.00 (2H, m), 2.10 (9H, s), 2.58 (2H, t, J = 7.6Hz ), 3.26 (4H, m), 3.36 (4H, m), 3.6 2 ~ 3.70 (2H; m), 3.75 (lH, m), 4.10 ~ 4.50 (3H, m), 4.84 (lH, d, J = 14.2Hz), 5.00 (lH, d, J = 13,8Hz), 5.12 (lH, d, J = 13.8Hz), 5.44 (lH, d, J = 14.2Hz), 6.90 (2H, < i, J = 8,9Hz), 6.94 (2H, s), 6.99 (2H, d, J = 8.9Hz), 7.03 (2H, d, J = 8.9Hz), 7.3l (lH, dd, J = 8.6, 2.0Hz), 7.43 (2H, d, J = 8.9Hz), 7.48 (lH, d, J = 2.0Hz), 7.62 (lH; s), 7.71 (lH, d, J = 8.6Hz), 7.90 (lH, s), 11.30 (lH, s). Example U (2R, 3R) -4- (4-ethylfluorenyloxy-3,5-dimethylfluorenyl) -1- 丨 3- 丨 4- (4-cyanophenyl) -fluorene Azol-2-yl〗 -2--2- (2,4-difluorophenyl) -2-hydroxy-butyl】 -1Η-Π, 2,41 triazole-4- Physical form: amorphous powder; FAB -MS: m / z 614 (M-Br) +; 1H-NMR (CD3OD) d 1.24 (3H, cU = 6.9Hz), 2.25 (6H, s), 2.36 (3H, s), 4.30 (lH, q , J = 6.9Hz), 4.64 (lH, d, J = 14.2Hz) s 5.10 (lH, d, J = 14.2Hz), 5.31 (2H, s), 6.75-7.27 (3Η? Ιη), --- __- 28 -___ This paper size applies Chinese National Standard (CNS) A4 (210X297). (Please read the precautions on the back before filling out this page.) ^ 15947 Λ7 '______B7_ V. Description of the invention (26) 7.10 ( 2H, s), 7.82 (2H, d, J = 8.3Hz), 8.09 (lH, s), 8118 (2H, d, J = 8.2Hz) > 8.73 (1H, s), 9. 95 (lH, s).

實例IS 溴化（2R，3R)-4-(4-胺基乙醯氧基-2-羧基4基）-1-丨3-丨4-(4-氰某 基V塞唑-2-基1-2-(2,4-二氟苯基）-2-經基丁基ΗΗ-Π，2,4〗***-4-德 三氟醋酸鹽 a) 3-(第三-丁氧羰基胺基乙醯氧基）-6-(溴基甲基）笨甲酸第 三-丁酯之製備 將200毫克3-羥基-6-(羥甲基）苯甲酸第三-丁酯、187毫克 Boc-甘胺酸、65毫克4-二曱胺基》比咬及245毫克1-(3-二甲胺 基丙基）-3-乙基碳化二亞胺鹽酸鹽在8毫升二氣甲烷中之混 合物，在室溫下攪拌〗5小時，並以40毫升二氣甲烷稀釋。 將此混合物以IN HC1洗滌，及以無水Na2S04乾燥。 移除溶劑，獲得180毫克3-(第三-丁氧羰基胺基乙醯氧基 )-6-羥甲基苯甲酸第三-丁酯。 經濟部中央標準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} 於650毫克3-(第三-丁氧羰基胺基乙醯氧基）-6-羥曱基苯甲 酸第三-丁酯與580毫克三苯膦之溶液中，添加848毫克四溴 化碳，並將混合物在室溫下攪拌2小時。將混合物以二氯 甲烷稀釋，並以水洗滌。有機層以無水N%S04乾燥，及在 眞空中濃縮。於矽膠上管柱層析獲得322毫克3-(第三-丁氧 羰基胺基乙醯氧基）-6-(溴基甲基）苯甲酸第三-丁酯，爲無 色油；W-NMiUCDCls) β 1.34(9H，s)7 1.51(9H,s)，4.08(2H，寬廣 d，J= 5.6Hz), 4.80(2H，s)，4.95(lH，寬廣 s)，7.12(lH,dd，J=8.6,2.6Hz)，7.34(lH，d，J= 8.6Hz), 7.51(lH,d,J=2.6Hz)= _______ .____- 29 -_______ l紙張尺度適用中國團家標隼（CNS ) A4规格（210)097公麓） 經濟部中央標準局負工消費合作社印製 A7 ___ B7 五、發明説明（27 ) b)溴化（2R,3R)-4-(4-胺基乙醯氧基-2-羧基苄基）-1-[3-[4-(4-氰基苯 基）》塞唑-2-基]-2-(2,4-二氟苯基）-2-羥基丁基]2,4]***-4-巍 三氟醋酸鹽，根據類似實例1之方式，自（1民2尺)-4-[2-[2-(2,4-二氟-苯基）-2-羥基小甲基-3-[1，2,4]***小基-丙基]-嘍唑>4·基]- 苯甲腈與3-(第三-丁氧羰基胺基乙醯氧基）-6-(溴基甲基）苯甲 酸第三·丁酯獲得，爲白色固體； 物理形式：白色粉末；？处-^18:111^645 (]\4-131〇+;111-N3VrR(CD3OD) δ 1.22(3H,d,J=7.3Hz),4.21(2H,s),4.28(lH,q,J=7.3Hz), 4.61(lH,dJ=14.2Hz)，5.09(lH，d，J=14.2Hz), 5.68(lH，dJ=14.0Hz)，5.75(lH，d,J =14.0Hz), 6.78-7.28(3H,m), 7.55(lH,dd,J=2.3,8.6Hz), 7.64(lH,d,J=8.6Hz), 7.81(2H,d,J=8.5Hz), 8.03(lH,d;J=2.3HzX 8.10(lH,s), 8.17(2H,d,J=8.5Hz), 8.67 (lH,s)} 9,80(lH,s)- 實例16 溴化1-丨(2R,3RV3-丨4-(4-氰基苯基V塞唑-2-基K~(2,4_二氟苯基）-2-巍基丁基M-丨(S)-3,5-二甲基-4-(四氫吡咯-2-羰基氧基）-苄基1-1H-[1，2,41***-4-巍三氟醋酸鹽 係藉下述方法A或B獲得。 i)方法A : 於3克溴化3,5-二甲基-4-羥基芊與CH3 CN (30毫升）之溶液 中，添加1.2克（1艮211)-4-[2-[2-(2,4-二氟苯基）-2-羥基小甲基-3· [1，2,4]***-1-基-丙基K唑-4-基]苯甲腈，並在室溫下持續攪 拌2小時。過濾沉澱物，並以醚洗滌而得1.37克（81 %產率） 溴化H(2R，3R)-3-[4-(4-氰基苯基 >塞唑-2-基]-2-(2+二氟苯基)-2_經 基丁基 Η-(3,5·二甲基-4-羥基）ΐ 基-1H-[1，2,4]***-4-銳(RO09-3846) —-------- 30 - —_____—-— 本紙張尺度適用中國國家標隼（CNS ) A4i^格（210X297公鰲） I ί —1 n * u - III · n —I 1= n n T 0¾.-0 (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消费合作社印製 41594? A7 B7五、發明説明（28 ) ，爲白色固體。 於30克溴化l-[(2R,3R)-3-[4-(4-氰基苯基）嘧唑-2-基]-2-(2,4-二氟-苯基）-2-羥基丁基]-4-(3,5-二甲基-4·裡苄基）-1Η[1,2,4]***-4遞、 10.9克Boc-(L)-脯胺酸及2.8克Ν,Ν-二甲胺基吡啶在1·2升二氣 甲烷中之混合物内，添加17.6克1-(3-二甲基胺基丙基）-3-乙 基碳化二亞胺鹽酸鹽，並將此混合物在室溫下攪拌1.5小時 ，及在眞空中濃縮。將殘留物於矽膠（Wakogel C-200，溶劑 :CH2Cl2/MeOH= M/1)上層析而得30.9克（79%產率）溴化1- [(2R,3R)-3-[4-(4-氰基苯基）嘍唑-2-基]·2-(2,4-二氟苯基）-2-羥基丁 基]-4-[(S)-3,5_二甲基-4-(N-第三-丁氧羰基四氮吡咯-2-羰基氧基） 苄基]-1Η-[1，2,4]***_4_鐵，爲白色固體。 在室溫下，將30.9克溴化l-[(2R，3R)-3-[4-(4-氰基苯基）嘍唑-2-基]-2_(2Λ二氟苯基）-2-羥基丁基]-4~[(S)-3,5-二甲基+(Ν-第三-丁 氧羰基四氫吡咯-2-羰基氧基）爷基]·1Η-[1,2,4]***-4说，在600 毫升10% TFA-二氣甲烷中攪拌5小時，並在眞空中移除溶 劑。將殘留物以醚稀釋，並以醚洗滌沉澱物，而得溴化1-[(211，311)-3-[4-(4-氰基苯基>塞唑-2-基]-2-(2,4-二氟苯基）-2-羥基丁 基H-[(S)-3,5-二甲基-4-(四氫吡咯-2-羰基氧基）爷基]-1Η-[1，2,4]三 唑-4-繞三氟醋酸鹽，爲白色固體。 ii)方法B : 將 1.06 克（lR，2R)-4-[2-[2-(2,4-二氟苯基）-2-羥基-1-甲基 ***-1-基-丙基]嘍唑冰基]苯甲腈，及以3個步驟製自3 5_二 甲基斗羥基苯甲醛之U克溴化3,5-二甲基-4-[(S)-N-第三-丁氧 羰基四氫吡咯-2-羰基氧基]字，在20毫井乙腈中之混合物， (請先閲讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家樣準（〇呢）六4規格（2丨0><297公釐） 415947 A7 B7 五、發明説明（29 ) 在回流溫度下攪拌15小時，然後濃縮。將殘留物於矽膠 (WakogelC-200，溶劑：CH2Cl2/MeOH =12/1)上層析，而得 1.92 克（94%產率）溴化1-[(2民311)_3-[4-(4-氰基苯基）嘧唑-2-基]-2-(2,4-二氟苯基）-2-羥基丁基]-4-[(S)-3,5-二甲基-4-(N-第三-丁氧羰基四 氫吡咯-2-羰基氧基）节基】·1Η-[1，2,4]***~4邊，爲白色固體。 按方法Α中所述，藉由移除保護基而獲得溴化i_[(2R，3R)-3-[4-(4-氰基苯基）喳唑-2-基]-2·(2,4-二氟苯基)-2-羥基丁基]-4-[(S)· 3,5-二甲基-4-(四氫吡咯-2-羰基氧基）爷基]-1H[1，2,4]***-4-銳三 氟醋酸鹽； 物理形式：白色粉末；从\1^1-1'0?-1^:111^669(1^-8〇+;1只-NMR (CD3 OD) i 1.24(3H,(U=7.3Hz)? 2.18-2.25(2H}m), 2.21(6H,s), 2.36- 2.44(lH,m)3 2.66-2.71(lH,m), 3.43-3.5,0(2H,m), 4.30(lH,q,J=7.3Hz), 4.65(lH,d,J=14.2Hz), 4.88(lH,m), 5.12(lH,d,J=14.2Hz), 5.33(2H,s), 6.73-6.79 6.99-7.06(lH,m)s 7.14(2H,s), 7.21-7.30(lH,m), 7.82(2H,d,J=8.6Hz), 8.10(lH,s)，8.18(2H，d,J=8.6Hz)，8.74(lH，s)，10.00(lH，s)。 於下述實例17-30中之化合物，係根據類似實例16之方式 獲得。 實例17 經濟部中央標準局貝工消费合作社印袋 (請先閲讀背面之注意事項再填寫本f ) 溴化（2R，3R)-4-(4-胺基乙醯氧基-3.5-二甲基芊基）-H3-丨4-(4-氰基 苯基）-嘍唑-2-基1-2-(2,4-二氟苯基）-2-羥基丁基Ί-1Η-Π,2,41***-4-崴三氟醋酸鹽； 物理形式：白色粉末；FAB-MS m/z 629 (M-Br)+ ; 1H-NMR CD3OD) δ 1.25(3H,d,J=7.3Hz),2.21(6H,s),4.29(lH,q,J=7.3Hz), .31(2H,s), 4.66(1 H,d,J=14.2Hz), 5.12(1ΗΛ>14.2Ηζ), 5.34(2H,s), 6.72-7.30 _______ 本紙張尺度適用中國國家榇準（CNS M4規格{210X 297公粲） 415947 經濟部中央橾準局負工消費合作社印裝 A? __B7__五、發明説明（30 ) 3H,m), 7.15(2H,s), 7.81(2H,d,J=6.6Hz), 8.10(lH,s), 8.17(2H,d,J=6.6Hz), 8.74( lH，s)，lO.O(lH’s)。 實例18 溴化（2反3尺)-4-丨4-(3-胺基丙醯氧基）-3,5-二甲基芊基1-1-[4-丨4-(4-氰 基苯基V嘧唑_2-基〗-2-(2,4-二氟苯基）-2-羥基-3-甲基丁基1-1H-『1，2,41***-4·娘三氟醋酸鹽； 物理形式·白色粉末；1;仙-廳：〇1/2 643(]^-丁17八-8〇+;1队 NMRCD3OD) J 1.24(3H,t,J=7.3Hz), 2.19(6H,s),3.09~3.37(4H,m), 4.30(lH，q，J=7.3Hz)，4,66(lH，d,J=14_2Hz)，5.1Κ1Η，(υ=14·2Ηζ)，5.33(2¾ 寬 廣 s)，6.73〜6.81(lH，m)，6.98-7.07(lH,m)，7.12(2H，s)，7.20-7.33(lH，m), 7.81(2H,d,J=6.9Hz), 8,10(lH,s)f 8.18(2H,d,J=6.9Hz), 8.74(lH,s), 10.00(lH,s) o 實例19 溴化（2R,3R)-4-丨4-(4-胺基丁醯氧基）-3,5-二甲基苄基1-H4-丨4-(4-氰 基苯基）-嚓唑-2-基〗-2-(2,4-二氟苯基）-2-羥基-3-甲基丁基1-1H-Π，2,41***-4-徽三氟醋酸鹽； 物理形式：白色粉末；FAB-MS:myz657(M-TFA·Br)+;lH-NMR(CD3OD) ci 1.24(3H,d,J=7.26Hz), 2.03-2.12(2H,m),2.17(6H,s), 2.87(2H,U=7.5Hz), 3.07(2H,t,J=7,5Hz), 4.30(lH,t,J=7.5Hz), 4.65(lH,d,J=14.4 Hz), 5.10(lH，cU=14.4Hz)，5_31(2H，s), 6,73-6.80(1Η，ιη)，6.98-7.07(lH，m), 7.11(2H,s), 7.18-7.28(lH,m), 7.82(2H,d,J=B.6Hz), 8.10(lH,s)s 8.17(2H,d，J=8.6Hz)，8.73(lH，s)。 實例20 溴化（2R,3R)-4-丨4-丨(2-胺基乙醯胺基）乙醯氧基1-3,5-二甲基芊基1- _-^L·_______ 本紙張尺度速用中國國家標準（CNS ) A4規格（210X 297公釐） (請先閱讀背面之注意事項再填寫本頁) 裝---- 經濟部中央榡準局員工消費合作社印製 41594? A7 ‘ B7五、發明説明（31 ) 1-[3-丨4~(4-氰基苯基）塞岭-2-基]-2-(2,4-二氟苯基）-2-經基丁基】-1H-丨U，4〗***·4·ϋ三氟醋酸鹽； 物理形式：白色粉末；FAB-MS : m/z 686 (M-Br)+ ; 1H-NMR (DMSO-de) S 1.18(3H,d,J=6.9Hz), 2.08(6H,s), 3.67(2H,brs), 4.14(lH,q,J=6.9Hz), 4.34(2H,d,J=5.6), 4.69(lH,d,J=l4.2Hz), 5.01(lH,d,J=14.2 Hz)? 5.35(2H,s), 6.58(lH,s), 6.90-6.96(lH,m), 7.07(2H,s), 7.21-7.37(2H,m), 7.94(2H，d，J=7.9Hz), 8.07(2H,寬廣 s), 8.21(2H，d，J=7.9Hz)，8.43(lH，s)， 8.99(m,t，J=5.6)，9.02(lH,s)，H).06(lH，s)。 實例21 溴化l-「(2R，3R)-3-丨4-(4-氰基苯基）-嘧唑-2-基卜2-(2,4-二氟苯基>2-羥基-丁基1-4-「4-阳)-2,5-二胺基戊醯基氧基1-3,5-二曱基芊基1-出-『1，2,41***-4-巍三氟醋酸鹽； 物理形式：白色粉末；FAB-MS : m/z 686 (M-Br)+ ; 1H-NMR (CD3OD) 1.24(3H，d，J=6.9Hz)，1.95-2.43(4H，m)，2_22(6H,s)，3 09 (2H,t,J=7.0Hz), 4.30(lH,q,J=6.9Hz), 4.60(1HM 4.67(1H,d,J=l4.2Hz), 5.12(1 H,d,J=14.2Hz)? 5.34(2H,s), 6.76-7.27(3H,m), 7.15(2H,s), 7.82(2H,d,J=8.2Hz), 810(lH，s), 8.18(2H,d,J=8.2Hz), 8.74(lH,s)，10.0(lH,s)。 實例22 溴化4-丨4-丨(8)-2-胺基丙醯氧基）-3,5-二甲基芊基1-1-丨(211,31〇-3-丨4-(4-氰基苯基）-嘧唑-2-基l-2-(2,4-二氟苯基）-2-幾基丁基〗-1Η-Π,2,41三 唑-4-鐵三氟醋酸鹽； 物理形式：白色粉末， FAB-MS : m/z 643 (Μ·Βγ)+ ; 1H-NMR (CD3OD) J 1.23(3H，d，J=6.9Hz)，l_79(3H，d,J=6.9Hz)，2.20(6H，s)， 4.29(lH,q,J=6.9Hz), 4.57(lH,q,J=6.9Hz), 4.67(lH,d,J=14.2Hz), 5.12(lH,d,J=l --------34 t__ 本紙張尺度適用中國國家標準（CNS } Λ4規格（210X 297公敍） (請先閲讀背面之注意事項再填寫本頁) 經濟部中央標準局負工消費合作社印聚 415947 A7 ^ B7 五、發明説明（32 ) 4.2Hz), 5.34(2H,s), 6.70-7.26(3H,m), 7.14(2H,s), 7.80(2H,d,J=8.2Hz), 8.10(lH,s)，8.18(2H,d，J=8.2Hz), 8.74(lH,s)，10.0(lH,s)。實例23 溴化1-丨(2尺,311)-3-丨4-(4-氰基苯基>塞唑-2-基1-2-(2,4-二氟苯基）-2-羥 基丁基Μ-Γ3,5-二甲基-4-丨(甲胺基）乙醯氧基1苄基1-1H-丨ί，2,4]三 唑-4-徹三氟醋酸鹽； 物理形式：非晶質粉末；FAB-MS : m/z 643 (M-Br)+ : 1H-NMR (CD3 0D) δ 1.24(3H,d,J=7.3Hz), 2.21(6H,s), 2.84(3H,s), 4.30(lH,q,J=7.3Hz), 4.45(2H,s), 4.65(lH,d,J=14.2Hz), 5.11(lH,d,J=14.2Hz), 5.33(2H,s), 6.76(lH,m) ,7.02(lH,m), 7.14(2H,s), 7.24(lH,m), 7.82(2H,d,J=8.6Hz), 8.10(lH,s), 8.18(2 H,d,J=8.6Hz), 8.74(lH，s), 9.99(lH，s)。實例24 溴化（2尺，311>1-[3-丨4-(4-氰基苯基>塞唑-2-基1-2-(2,4-二氟苯基）-2-羥 基丁基1-4-丨3,5-二甲基-4-丨(丙胺基）乙醯氧基1芊基1-1H-丨1,2,41三 唑-4-巍三氟醋酸鹽； 物理形式：白色粉末；FAB-MS : m/z 6Ή (M-Br)+ ; 1H-NMR (CD3OD) 1.05(3ΗΛ^7.4Ηζ), 1.25(3H,d,J=7.3Hz), 1.77(2H,m), 2.21(6H,s), 3.10(2H,m), 4.31(lH,q,J=7.4Hz), 4.47(2H,s), 4.66(lH,d,J=13.9Hz)} 5.12(lH,d, J=13.9Hz), 5.33(2H,s), 6.72-7.29(3H,m), 7.14(2H,s), 7.82(2H,dtJ=8.3Hz), 8.09(lH，s)，8.18(2H，d，J=8.3Hz), 8.74(liis)，10.0(lH,s)。實例25 溴化1-丨(2R、3RV3-丨4-(4-氰基苯基V塞唑-2-基1-2-(2,4-二氟苯基）-2-羥 基丁基1-4-丨4-【⑸-2-(甲胺基）丙醯氡基1-3,5-二甲基芊基ΗΗ-Π,2,41 ***-4·^三氟醋酸鹽； ----35-_ 本紙張尺度適用中國國家標準（CNS ) Α4+規格（2】0Χ297公釐） (請先閲讀背面之注意事項再填寫本育} 經濟部中央榡準局員工消費合作枉印製 415947 Λ7 ' B7五、發明説明（33 ) 物理形式：白色粉末；FAB-MS : m/z 657 (M-Br)+ ; 1H-NMR (CD3OD) δ 1.25(3H,d,J=7-3Hz), 1.83(3H,d,J=7.3Hz), 2.21(6H,s), 2.83(3H,s), 4.26(1 H,q,J=7.3Hz)} 4.57(lH,q,J=7.3Hz), 4.66(lH,d,J=14.5Hz), 5.12(lH,d,J=l 4.5Hz), 5.34(2H,s), 6.72-7.26(3Hsm)? 7.15(2H,s), 7.82(2H,d,J=8.6Hz), 8.11(lH，s)，8,18(2H，d,J=8.6Hz), 8.75(lH，s)。 實例26 溴化（2R,3R)-1-丨4-丨4-(4-氰基笨基 >塞唑-2-基l-2-(2,4-二氟苯基）-2-羥 基-3-甲基丁基M-丨3,5-二甲基-4-丨3-(甲胺基）丙醯氧基件基HH-Γ1，2,41***-4-巍三氟醋酸鹽； 物理形式：白色粉末；？灿-^18:111/2 657 (1^-丁?八-81")+;115-NMR (CD3 0D) δ 1.24(3H,d,J=6.9Hz), 2.19(6H,s), 2.78(3H,s), 3.21(2H,t,J=6.6Hz), 3.42(2H,t,J=6.6Hz), 4.30(lH,q,J=6.9Hz), 4.66(lH,d,J=14.2 Hz), 5.11(lH,d,J=14.2Hz), 5.33(2H,s), 6.73~6.81(lH,m)? 6.98-7.07(1H,m), 7.12(2H,s), 7.20-7.30(1 H,m), 7.82(2H,d,J=8.7Hz), 8.10(lH,s), 8.18(2H,£U=8.7Hz), 8.73(1H,s), 9.98(1H,s) 〇 實例27 溴化4-丨4-丨(S)-2-胺基-3-甲基丁醯氧基1-3,6-二甲基芊基1-1-f(2R，3R)-3-丨4-(4-氰基笨基）嘍唑-2-基1-2-(2,4-二氟-苯基）-2-羥基丁 基1-识-丨1,2,41***冰鐵三氟醋酸鹽； 物理形式：白色粉末；FAB-MS : m/z671 ; 1H-NMR (CD3OD) β l,21(3H，d，J=6.9Hz)，1.25(3H,tU=6.9Hz), 1.27(3H，ci，J=6.9Hz), 2.22(6H,s), 2.66(lH,m), 4.27(lH,q,J=6.9Hz), 4.49(lH,d,J=3.6Hz), 4.66(lH,d,J =14.2Hz)，5.12(lH,d,J=14.2Hz), 5_35(2H，s)，6.73-7.30(3H，m)，7.16(2H,s), 7.82(2H，d，J=8.6Hz), 8.10(lH，s)，8.18(2H，d，J=8_6Hz), 8.75(lH，s), 10.0(lH，s) —>*__—_____ ~ 36 ~_______ 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公犮） n ϊ - ·. * - -- -- - f I I I ici i —1. t i I 、-='e (請先閱讀背面之注意事項再填寫本頁)Example IS Brominated (2R, 3R) -4- (4-aminoethanyloxy-2-carboxy4yl) -1- 丨 3- 丨 4- (4-cyano-Vethazol-2-yl 1-2- (2,4-difluorophenyl) -2-Ethylbutylfluorene-Π, 2,4〗 triazole-4-detrifluoroacetate a) 3- (third-butoxycarbonyl Preparation of Amino-Ethyloxy) -6- (bromomethyl) tertiary-butyl benzoate 200 mg of 3-hydroxy-6- (hydroxymethyl) benzoic acid tertiary-butyl ester, 187 mg Boc -Glycine, 65 mg of 4-diamidoamine, and 245 mg of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride in 8 ml of digas methane The mixture was stirred at room temperature for 5 hours and diluted with 40 ml of digas methane. The mixture was washed with IN HC1 and dried over anhydrous Na2S04. The solvent was removed to obtain 180 mg of 3- (third-butoxycarbonylaminoacetamido) -6-hydroxymethylbenzoic acid tert-butyl ester. Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) at 650 mg To a solution of tert-butyl ester and 580 mg of triphenylphosphine, 848 mg of carbon tetrabromide was added, and the mixture was stirred at room temperature for 2 hours. The mixture was diluted with dichloromethane and washed with water. The organic layer was treated with Anhydrous N% S04 was dried and concentrated in the air. The column chromatography on silica gel gave 322 mg of 3- (third-butoxycarbonylaminoethoxy) -6- (bromomethyl) benzoic acid. Tri-butyl ester, colorless oil; W-NMiUCDCls) β 1.34 (9H, s) 7 1.51 (9H, s), 4.08 (2H, Broad d, J = 5.6Hz), 4.80 (2H, s), 4.95 ( lH, broad s), 7.12 (lH, dd, J = 8.6,2.6Hz), 7.34 (lH, d, J = 8.6Hz), 7.51 (lH, d, J = 2.6Hz) = _______ .____- 29- _______ l The paper size is applicable to the Chinese group house standard (CNS) A4 (210) 097 feet. Printed by the Consumers ’Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. A7 ___ B7 V. Description of the invention (27) b) Bromination (2R, 3R) -4- (4-Aminoethoxy-2-carboxybenzyl) -1- [3- [4- (4-cyanophenyl) "Sepazol-2-yl] -2- (2,4-difluorophenyl) -2-hydroxybutyl] 2,4] triazole-4-trifluoroacetate According to a manner similar to Example 1, from (1 min 2 ft) -4- [2- [2- (2,4-difluoro-phenyl) -2-hydroxy small methyl-3- [1,2, 4] triazolyl-propyl] -oxazole> 4-yl] -benzonitrile with 3- (third-butoxycarbonylaminoethylacetoxy) -6- (bromomethyl) benzene Tert-butyl formate was obtained as a white solid; physical form: white powder; Division-^ 18: 111 ^ 645 () \ 4-131〇 +; 111-N3VrR (CD3OD) δ 1.22 (3H, d, J = 7.3Hz), 4.21 (2H, s), 4.28 (lH, q, J = 7.3Hz), 4.61 (lH, dJ = 14.2Hz), 5.09 (lH, d, J = 14.2Hz), 5.68 (lH, dJ = 14.0Hz), 5.75 (lH, d, J = 14.0Hz), 6.78 -7.28 (3H, m), 7.55 (lH, dd, J = 2.3,8.6Hz), 7.64 (lH, d, J = 8.6Hz), 7.81 (2H, d, J = 8.5Hz), 8.03 (lH, d; J = 2.3HzX 8.10 (lH, s), 8.17 (2H, d, J = 8.5Hz), 8.67 (lH, s)) 9,80 (lH, s)-Example 16 Bromide 1- 丨 (2R , 3RV3- 丨 4- (4-cyanophenyl V selazol-2-yl K ~ (2,4-difluorophenyl) -2-weitylbutyl M- 丨 (S) -3,5- Dimethyl-4- (tetrahydropyrrole-2-carbonyloxy) -benzyl 1-1H- [1,2,41triazole-4-trifluorotrifluoroacetate is obtained by the following method A or B. i) Method A: To a solution of 3 g of 3,5-dimethyl-4-hydroxyphosphonium bromide and CH3 CN (30 ml), add 1.2 g (1,211) -4- [2- [2- (2,4-difluorophenyl) -2-hydroxy small methyl-3 · [1,2,4] triazol-1-yl-propylKazol-4-yl] benzonitrile, and Stirring was continued at room temperature for 2 hours. The precipitate was filtered and washed with ether to obtain 1.37 g (81% yield) of H (2R, 3R) -3- [4- (4-cyanophenyl) > -2-yl] -2- (2 + difluorophenyl) -2-merylbutylfluorene- (3,5 · Dimethyl-4-hydroxy) fluorenyl-1H- [1,2,4] triazole-4-rule (RO09-3846) —-------- 30-—_____—-— This paper Standards apply to Chinese National Standards (CNS) A4i ^ (210X297), I ί —1 n * u-III · n —I 1 = nn T 0¾.-0 (Please read the notes on the back before filling this page ) 41594 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (28) is a white solid. At 30 g bromide l-[(2R, 3R) -3- [4- (4-cyanide Phenyl) pyrazol-2-yl] -2- (2,4-difluoro-phenyl) -2-hydroxybutyl] -4- (3,5-dimethyl-4 · ribenzyl) -1Η [1,2,4] triazole-4 di, 10.9 g of Boc- (L) -proline and 2.8 g of N, N-dimethylaminopyridine in 1.2 liters of digasmethane , 17.6 g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride was added, and the mixture was stirred at room temperature for 1.5 hours, and concentrated in the air. The residue was chromatographed on silica gel (Wakogel C-200, solvent: CH2Cl2 / MeOH = M / 1) to obtain 30.9 g (79% yield) of bromide 1-[(2R, 3R) -3- [4- (4-cyanophenyl) oxazol-2-yl] · 2- (2,4-difluorophenyl) -2-hydroxybutyl] -4-[(S) -3,5-dimethyl -4- (N-Third-butoxycarbonyltetraazapyrrole-2-carbonyloxy) benzyl] -1 '-[1,2,4] triazole-4- iron, as a white solid. At room temperature, 30.9 g of l-[(2R, 3R) -3- [4- (4-cyanophenyl) oxazol-2-yl] -2_ (2Λdifluorophenyl) -2 -Hydroxybutyl] -4 ~ [(S) -3,5-dimethyl + (N-third-butoxycarbonyltetrahydropyrrole-2-carbonyloxy) methyl] · 1Η- [1,2 , 4] Triazole-4, stirred in 600 ml of 10% TFA-digas methane for 5 hours, and the solvent was removed in the air. The residue was diluted with ether, and the precipitate was washed with ether to give 1-[(211,311) -3- [4- (4-cyanophenyl > sezol-2-yl] -2 -(2,4-difluorophenyl) -2-hydroxybutyl H-[(S) -3,5-dimethyl-4- (tetrahydropyrrole-2-carbonyloxy) methyl] -1Η -[1,2,4] triazole-4-trifluoroacetate as a white solid. Ii) Method B: 1.06 g of (lR, 2R) -4- [2- [2- (2,4- Difluorophenyl) -2-hydroxy-1-methyltriazol-1-yl-propyl] oxazolebenzyl] benzonitrile, and 3 5-dimethylpyridoxal benzaldehyde in 3 steps A mixture of U g of 3,5-dimethyl-4-[(S) -N-third-butoxycarbonyltetrahydropyrrole-2-carbonyloxy] in 20 milliwells of acetonitrile, ( Please read the notes on the back before filling in this page) This paper size is applicable to Chinese national standards (〇 呢) 6 4 specifications (2 丨 0 > < 297 mm) 415947 A7 B7 V. Description of the invention (29) Reflow Stir at temperature for 15 hours and then concentrate. The residue was chromatographed on silica gel (WakogelC-200, solvent: CH2Cl2 / MeOH = 12/1) to obtain 1.92 g (94% yield) of bromide 1-[(2min 311) _3- [4- ( 4-cyanophenyl) pyrazol-2-yl] -2- (2,4-difluorophenyl) -2-hydroxybutyl] -4-[(S) -3,5-dimethyl- 4- (N-Third-butoxycarbonyltetrahydropyrrole-2-carbonyloxy) benzyl] · 1Η- [1,2,4] triazole ~ 4 sides, as a white solid. As described in Method A, i _ [(2R, 3R) -3- [4- (4-cyanophenyl) oxazol-2-yl] -2 · (2 , 4-difluorophenyl) -2-hydroxybutyl] -4-[(S) · 3,5-dimethyl-4- (tetrahydropyrrole-2-carbonyloxy) methyl] -1H [ 1,2,4] triazole-4-atrifluoroacetate; physical form: white powder; from \ 1 ^ 1-1'0? -1 ^: 111 ^ 669 (1 ^ -8〇 +; 1 only -NMR (CD3 OD) i 1.24 (3H, (U = 7.3Hz)? 2.18-2.25 (2H) m), 2.21 (6H, s), 2.36- 2.44 (lH, m) 3 2.66-2.71 (lH, m ), 3.43-3.5,0 (2H, m), 4.30 (lH, q, J = 7.3Hz), 4.65 (lH, d, J = 14.2Hz), 4.88 (lH, m), 5.12 (lH, d, J = 14.2Hz), 5.33 (2H, s), 6.73-6.79 6.99-7.06 (lH, m) s 7.14 (2H, s), 7.21-7.30 (lH, m), 7.82 (2H, d, J = 8.6 Hz), 8.10 (lH, s), 8.18 (2H, d, J = 8.6 Hz), 8.74 (lH, s), 10.00 (lH, s). The compounds in Examples 17-30 below are based on similar Obtained in the manner of Example 16. Example 17 Printed bags of the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling in this f) Bromide (2R, 3R) -4- (4-aminoethylacetoxy) -3.5-dimethylfluorenyl) -H3- 丨 4- (4-cyanophenyl) -oxazol-2-yl 1-2- (2,4-difluorophenyl) -2-hydroxy Hydrazone-1Ί-Π, 2,41triazole-4- 崴 trifluoroacetate; physical form: white powder; FAB-MS m / z 629 (M-Br) +; 1H-NMR CD3OD) δ 1.25 (3H , d, J = 7.3Hz), 2.21 (6H, s), 4.29 (lH, q, J = 7.3Hz), .31 (2H, s), 4.66 (1 H, d, J = 14.2Hz), 5.12 (1ΗΛ &1; 14.2Ηζ), 5.34 (2H, s), 6.72-7.30 _______ This paper size is applicable to China National Standards (CNS M4 specification {210X 297 public address) 415947 Printed by the Consumer Affairs Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs __B7__ V. Description of the invention (30) 3H, m), 7.15 (2H, s), 7.81 (2H, d, J = 6.6Hz), 8.10 (lH, s), 8.17 (2H, d, J = 6.6 Hz), 8.74 (lH, s), lO.O (lH's). Example 18 Bromide (2-trans-3ft) -4- 丨 4- (3-aminopropylfluorenyloxy) -3,5-dimethylfluorenyl 1-1- [4- 丨 4- (4-cyano Phenylphenyl Vpyrazole_2-yl〗 -2- (2,4-difluorophenyl) -2-hydroxy-3-methylbutyl1-1H- "1,2,41triazole-4 · Tris (trifluoroacetate); Physical form · White powder; 1; Sin-hall: 〇1 / 2 643 () ^-丁 17 八 -8〇 +; Team 1 NMRCD3OD) J 1.24 (3H, t, J = 7.3Hz ), 2.19 (6H, s), 3.09 ~ 3.37 (4H, m), 4.30 (lH, q, J = 7.3Hz), 4,66 (lH, d, J = 14_2Hz), 5.1Κ1Η, (υ = 14 · 2Ηζ), 5.33 (2¾ wide s), 6.73 ~ 6.81 (lH, m), 6.98-7.07 (lH, m), 7.12 (2H, s), 7.20-7.33 (lH, m), 7.81 (2H, d , J = 6.9Hz), 8,10 (lH, s) f 8.18 (2H, d, J = 6.9Hz), 8.74 (lH, s), 10.00 (lH, s) o Example 19 Bromination (2R, 3R ) -4- 丨 4- (4-Aminobutyryloxy) -3,5-dimethylbenzyl 1-H4- 丨 4- (4-cyanophenyl) -oxazol-2-yl -2- (2,4-difluorophenyl) -2-hydroxy-3-methylbutyl 1-1H-Π, 2,41 triazole-4-hui trifluoroacetate; Physical form: white powder; FAB-MS: myz657 (M-TFA · Br) +; lH-NMR (CD3OD) ci 1.24 (3H, d, J = 7.26Hz), 2.03-2.12 (2H, m), 2.17 (6H, s), 2.87 (2H, U = 7.5Hz), 3.07 (2H, t, J = 7,5Hz), 4.30 (lH, t, J = 7.5Hz), 4.6 5 (lH, d, J = 14.4 Hz), 5.10 (lH, cU = 14.4Hz), 5_31 (2H, s), 6,73-6.80 (1Η, ιη), 6.98-7.07 (lH, m), 7.11 (2H, s), 7.18-7.28 (lH, m), 7.82 (2H, d, J = B.6Hz), 8.10 (lH, s) s 8.17 (2H, d, J = 8.6Hz), 8.73 (lH , S). Example 20 (2R, 3R) -4- (4-amino (2-aminoethylamido) ethoxy) ethoxy-3-, 5-dimethylfluorenyl 1 -_- ^ L · _______ This paper is a quick-use Chinese National Standard (CNS) A4 specification (210X 297 mm) (please read the precautions on the back before filling this page). Packing ---- Printed by the Consumers Cooperative of the Central Procurement Bureau of the Ministry of Economic Affairs 41594? A7 'B7 V. Description of the invention (31) 1- [3- 丨 4 ~ (4-cyanophenyl) seling-2-yl] -2- (2,4-difluorophenyl)- 2-Ethylbutyl] -1H- 丨 U, 4〗 triazole · 4 · fluorene trifluoroacetate; physical form: white powder; FAB-MS: m / z 686 (M-Br) +; 1H-NMR (DMSO-de) S 1.18 (3H, d, J = 6.9Hz), 2.08 (6H, s), 3.67 (2H, brs), 4.14 (lH, q, J = 6.9Hz), 4.34 (2H, d, J = 5.6), 4.69 (lH, d, J = l4.2Hz), 5.01 (lH, d, J = 14.2 Hz)? 5.35 (2H, s), 6.58 (lH, s), 6.90-6.96 (lH, m), 7.07 (2H, s), 7.21-7.37 (2H, m), 7.94 (2H, d, J = 7.9Hz), 8.07 (2H, broad s), 8.21 (2H, d, J = 7 .9 Hz), 8.43 (lH, s), 8.99 (m, t, J = 5.6), 9.02 (lH, s), H) .06 (lH, s). Example 21 1-"(2R, 3R) -3- 丨 4- (4-cyanophenyl) -pyrimazol-2-ylb 2- (2,4-difluorophenyl) 2-hydroxyl -Butyl 1-4- "4-yang) -2,5-diaminopentylfluorenyloxy 1-3,5-difluorenylfluorenyl 1-out-" 1,2,41triazole-4 -Wei trifluoroacetate; Physical form: white powder; FAB-MS: m / z 686 (M-Br) +; 1H-NMR (CD3OD) 1.24 (3H, d, J = 6.9Hz), 1.95-2.43 ( 4H, m), 2_22 (6H, s), 3 09 (2H, t, J = 7.0Hz), 4.30 (lH, q, J = 6.9Hz), 4.60 (1HM 4.67 (1H, d, J = l4. 2Hz), 5.12 (1 H, d, J = 14.2Hz)? 5.34 (2H, s), 6.76-7.27 (3H, m), 7.15 (2H, s), 7.82 (2H, d, J = 8.2Hz) , 810 (lH, s), 8.18 (2H, d, J = 8.2Hz), 8.74 (lH, s), 10.0 (lH, s). Example 22 Bromide 4- 丨 4- 丨 (8) -2- Aminopropylamidooxy) -3,5-dimethylfluorenyl 1-1-1 (211,31〇-3- 丨 4- (4-cyanophenyl) -pyrazol-2-yl 1- 2- (2,4-difluorophenyl) -2-chitylbutyl} -1Η-Π, 2,41triazole-4-iron trifluoroacetate; Physical form: white powder, FAB-MS: m / z 643 (Μ · Βγ) +; 1H-NMR (CD3OD) J 1.23 (3H, d, J = 6.9Hz), l_79 (3H, d, J = 6.9Hz), 2.20 (6H, s), 4.29 ( lH, q, J = 6.9Hz), 4.57 (lH, q, J = 6.9Hz), 4.67 (lH, d, J = 14.2Hz), 5.12 (lH, d, J = l ---- ---- 34 t__ This paper size applies to Chinese National Standards (CNS) Λ4 size (210X 297 public narrative) (Please read the precautions on the back before filling this page) Central Office of Standards, Ministry of Economic Affairs, Consumer Cooperatives, India, Juju 415947 A7 ^ B7 V. Description of the invention (32) 4.2Hz), 5.34 (2H, s), 6.70-7.26 (3H, m), 7.14 (2H, s), 7.80 (2H, d, J = 8.2Hz), 8.10 ( lH, s), 8.18 (2H, d, J = 8.2Hz), 8.74 (lH, s), 10.0 (lH, s). Example 23 Bromide 1- 丨 (2 feet, 311) -3- 丨 4- (4-cyanophenyl > sedazol-2-yl1-2- (2,4-difluorophenyl) -2-hydroxybutyl M-Γ3,5-dimethyl-4- 丨 (formaldehyde Amine group) Ethyloxy 1 benzyl 1-1H- 丨, 2,4] triazole-4-tritrifluoroacetate; Physical form: amorphous powder; FAB-MS: m / z 643 (M- Br) +: 1H-NMR (CD3 0D) δ 1.24 (3H, d, J = 7.3Hz), 2.21 (6H, s), 2.84 (3H, s), 4.30 (lH, q, J = 7.3Hz), 4.45 (2H, s), 4.65 (lH, d, J = 14.2Hz), 5.11 (lH, d, J = 14.2Hz), 5.33 (2H, s), 6.76 (lH, m), 7.02 (lH, m ), 7.14 (2H, s), 7.24 (lH, m), 7.82 (2H, d, J = 8.6Hz), 8.10 (lH, s), 8.18 (2 H, d, J = 8.6Hz), 8.74 ( lH, s), 9.99 (lH, s). Example 24 Bromination (2 feet, 311 > 1- [3- 丨 4- (4-cyanophenyl > sedazol-2-yl 1-2- (2,4-difluorophenyl) -2- Hydroxybutyl 1-4- 丨 3,5-dimethyl-4- 丨 (propylamino) ethoxyl 1-hydroxyl 1-1H- 丨 1,2,41triazole-4-trifluoroacetate ; Physical form: white powder; FAB-MS: m / z 6Ή (M-Br) +; 1H-NMR (CD3OD) 1.05 (3ΗΛ ^ 7.4Ηζ), 1.25 (3H, d, J = 7.3Hz), 1.77 ( 2H, m), 2.21 (6H, s), 3.10 (2H, m), 4.31 (lH, q, J = 7.4Hz), 4.47 (2H, s), 4.66 (lH, d, J = 13.9Hz)) 5.12 (lH, d, J = 13.9Hz), 5.33 (2H, s), 6.72-7.29 (3H, m), 7.14 (2H, s), 7.82 (2H, dtJ = 8.3Hz), 8.09 (lH, s ), 8.18 (2H, d, J = 8.3Hz), 8.74 (liis), 10.0 (lH, s). Example 25 1- 丨 (2R, 3RV3- 丨 4- (4-cyanophenyl V plug) bromide Azole-2-yl1-2- (2,4-difluorophenyl) -2-hydroxybutyl1-4- 丨 4- [fluorene-2- (methylamino) propanyl 1-3, 5-dimethylfluorenylfluorene-Π, 2,41 triazole-4 · ^ trifluoroacetate; ---- 35-_ This paper size applies to China National Standard (CNS) Α4 + Specification (2) 0 × 297 mm ) (Please read the notes on the back before filling in this education} Printed by the Central Government of the Ministry of Economic Affairs, Consumer Cooperation, 415947 Λ7 'B7 V. Invention Ming (33) Physical form: white powder; FAB-MS: m / z 657 (M-Br) +; 1H-NMR (CD3OD) δ 1.25 (3H, d, J = 7-3Hz), 1.83 (3H, d , J = 7.3Hz), 2.21 (6H, s), 2.83 (3H, s), 4.26 (1 H, q, J = 7.3Hz)) 4.57 (lH, q, J = 7.3Hz), 4.66 (lH, d, J = 14.5Hz), 5.12 (lH, d, J = l 4.5Hz), 5.34 (2H, s), 6.72-7.26 (3Hsm)? 7.15 (2H, s), 7.82 (2H, d, J = 8.6Hz), 8.11 (lH, s), 8,18 (2H, d, J = 8.6Hz), 8.75 (lH, s). Example 26 Bromination (2R, 3R) -1- 丨 4- 丨 4- (4-cyanobenzyl > sedazol-2-yll-2- (2,4-difluorophenyl) -2-hydroxy-3-methylbutyl M- 丨 3,5-dimethyl -4- 丨 3- (methylamino) propanyloxy group HH-Γ1,2,41triazole-4-titanium trifluoroacetate; Physical form: white powder;? Can- ^ 18: 111/2 657 (1 ^-丁? 八 -81 ")+; 115-NMR (CD3 0D) δ 1.24 (3H, d, J = 6.9Hz), 2.19 (6H, s), 2.78 (3H, s), 3.21 (2H, t, J = 6.6Hz), 3.42 (2H, t, J = 6.6Hz), 4.30 (lH, q, J = 6.9Hz), 4.66 (lH, d, J = 14.2 Hz), 5.11 (lH, d, J = 14.2Hz), 5.33 (2H, s), 6.73 ~ 6.81 (lH, m)? 6.98-7.07 (1H, m), 7.12 (2H, s), 7.20- 7.30 (1 H, m), 7.82 (2H, d, J = 8.7Hz), 8.10 (lH, s), 8.18 (2H, £ U = 8.7Hz), 8.73 (1H, s), 9.98 (1H, s ) 〇 Example 27 4- 丨 4- 丨 (S) -2-amino-3-methylbutanyloxy 1-3,6-dimethylfluorenyl 1-1-f (2R, 3R) -3- 丨 4- (4-Cyanobenzyl) oxazol-2-yl 1-2- (2,4-difluoro-phenyl) -2-hydroxybutyl 1-1,2, 41 Triazole ferric trifluoroacetate; Physical form: white powder; FAB-MS: m / z671; 1H-NMR (CD3OD) β 1,21 (3H, d, J = 6.9Hz), 1.25 (3H, tU = 6.9Hz), 1.27 (3H, ci, J = 6.9Hz), 2.22 (6H, s), 2.66 (lH, m), 4.27 (lH, q, J = 6.9Hz), 4.49 (lH, d, J = 3.6Hz), 4.66 (lH, d, J = 14.2Hz), 5.12 (lH, d, J = 14.2Hz), 5_35 (2H, s), 6.73-7.30 (3H, m), 7.16 (2H, s ), 7.82 (2H, d, J = 8.6Hz), 8.10 (lH, s), 8.18 (2H, d, J = 8_6Hz), 8.75 (lH, s), 10.0 (lH, s) — > * __ —_____ ~ 36 ~ _______ Paper The scale is applicable to the Chinese National Standard (CNS) A4 specification (210X297 cm) n ϊ-·. *----F III ici i —1. Ti I 、-= 'e (Please read the precautions on the back first (Fill in this page again)

41594? 第86丨丨7223^:專利申請案 A7 屮文說明書修正頁(88年12月)_B7 五、發明説明（34) 實例28 >矣化（21;1,3{^)-丨-[~3-[~4-(4-底基私基）-»塞吐-2-基1-2-(2,4-二氣苯基）-2-羥基-丁基1-4-丨4-丨(異丙基胺基）乙醯氧基〗-3、5-二甲基芊基1-1H-Π,2,41***-4- 三氟醋酸鹽；41594? Section 86 丨 丨 7223 ^: Revised page of patent application A7 manuscript specification (December 88) _B7 V. Description of invention (34) Example 28 > Huahua (21; 1,3 {^)-丨- [~ 3- [~ 4- (4-Substrate private group)-»Setup-2-yl1-2- (2,4-difluorophenyl) -2-hydroxy-butyl1-4- 丨4- 丨 (isopropylamino) ethoxyloxy-3,5-dimethylfluorenyl 1-1H-Π, 2,41triazole-4-trifluoroacetate;

物理形式：非晶質粉末；FAB-MS : m/z671 (M-Br)+ ; lH-NMR (CD3OD) o 1.24(3H，d，J=6.9Hz)，1.41(6H，cU=6.6Hz)，2.22(6H，s)，3.32-3.53 4.30(lH,qjJ=7.3Hz), 4.50(2H,s); 4.66(lH,d,J=14.2Hz), 5.12(lH,d5J=14. 2Hz), 5.34(2H,s)3 6.73-6.78(lH,m), 6.98-7.06(lH,m), 7.15(2H,s), 7.20〜7.29(lH，m), 7.82(2H,d，J=8.6Hz), 8.1 l(lH,s), 8.18(2H，d，J=8.6Hz), 8.74(1 H，s)。 實例29 溴化卜R(2R,3R)-3-丨4-(4-氰基苯基V塞唑-2-基〗-2-(2,4-二氟苯基）-2-羥基丁基M-丨(2SV4-丨乙胺基）丙醯氧基1-3>二甲基苄基〗-1沁 「1,2,41三吐-4- 三氟醋酸鹽；. 物理形式：非晶質粉末；MALDI-TOF-MS : m/z671 (M-Br)+ ; 1 H-NMR (CD3 OD) 5 1.24(3H,d,J=7.3Hz), 1.38(3H,t,J=7.3Hz), I.83(3H,d,J^7.3Hz), 2.21(6H,s), 3.14-3.25(2H,m), 4.30(lH,q,J=7.3Hz), 4.63(lH,q,J=7.3Hz), 4.66(lH1d,J=14.2Hz), 5.12(lH,d,J=14.2Hz), 5.35(2H,s), 6. 74~6.80(lH,m), 6.98-7.07(lH,m), 7.16(2H,s), 7.21- 7.30(1^1X1), 7.82(2H,d,J=8.6Hz), 8.11(lH,s), 8.18(2H,d,J=8.6Hz), 8.75(lH,s), 10.00( 1 H，s)。 f例30 溴化（2IURH-P-丨4-(4-氰基苯基）--塞唑-2-基1-2-(2,4-二氟苯基）-2- -37- 本紙張尺度適用中國國家標準（CNS ) A4規格（2丨0X297公釐） (請先閲讀背面之注意事項再填寫本頁)Physical form: amorphous powder; FAB-MS: m / z671 (M-Br) +; lH-NMR (CD3OD) o 1.24 (3H, d, J = 6.9Hz), 1.41 (6H, cU = 6.6Hz) , 2.22 (6H, s), 3.32-3.53 4.30 (lH, qjJ = 7.3Hz), 4.50 (2H, s); 4.66 (lH, d, J = 14.2Hz), 5.12 (lH, d5J = 14. 2Hz) , 5.34 (2H, s) 3 6.73-6.78 (lH, m), 6.98-7.06 (lH, m), 7.15 (2H, s), 7.20 ~ 7.29 (lH, m), 7.82 (2H, d, J = 8.6Hz), 8.1 l (lH, s), 8.18 (2H, d, J = 8.6Hz), 8.74 (1 H, s). Example 29 Br (2R, 3R) -3- 丨 4- (4-cyanophenyl Vselazol-2-yl) -2- (2,4-difluorophenyl) -2-hydroxybutyl M- 丨 (2SV4- 丨 Ethylamino) propanyloxy 1-3 > dimethylbenzyl〗 -1, "1,2,41 Tritul-4-trifluoroacetate; Physical form: Non Crystalline powder; MALDI-TOF-MS: m / z671 (M-Br) +; 1 H-NMR (CD3 OD) 5 1.24 (3H, d, J = 7.3Hz), 1.38 (3H, t, J = 7.3 Hz), I.83 (3H, d, J ^ 7.3Hz), 2.21 (6H, s), 3.14-3.25 (2H, m), 4.30 (lH, q, J = 7.3Hz), 4.63 (lH, q , J = 7.3Hz), 4.66 (lH1d, J = 14.2Hz), 5.12 (lH, d, J = 14.2Hz), 5.35 (2H, s), 6. 74 ~ 6.80 (lH, m), 6.98-7.07 (lH, m), 7.16 (2H, s), 7.21- 7.30 (1 ^ 1X1), 7.82 (2H, d, J = 8.6Hz), 8.11 (lH, s), 8.18 (2H, d, J = 8.6 Hz), 8.75 (lH, s), 10.00 (1H, s). FExample 30 Brominated (2IURH-P- 丨 4- (4-cyanophenyl)-sepazol-2-yl 1-2 -(2,4-Difluorophenyl) -2- -37- This paper size applies to Chinese National Standard (CNS) A4 (2 丨 0X297 mm) (Please read the precautions on the back before filling this page)

11T 經濟部中央樣隼局員工消費合作社印製 415947 A7 ____B7 五、發明説明（35 ) (請先閱讀背面之注意事項再填寫本頁 羥基丁基1-4-丨4-『(乙胺基）乙醯氧基1-3,5-二甲基苄基1-1H-丨1，2,41 ***-4-撤三氟醋酸鹽； 物理形式：白色粉末；FAB-MS : m/z 657 (M-Br)+ ; 1H-NMR (CD3OD) δ 1.25(3H,d,J=7.3Hz)i 1.38(3H,U=7.3Hz), 2.22(6H,s), 3.22(2H,q,J=7.3Hz), 4.27(1 H,q,J=7.3Hz), 4.48(2H,s), 4.67(lH,d,J=14.2Hz), 5.1 2(lH,d,J=14.2Hz), 5.35(2H,s), 6.73-7.29(3H^n), 7.15(2H,s), 7.82(2H,d,J=8.6Hz), 8.10(lH,s), 8.18(2H,d,J=8.6Hz), 8.75(lH,s), 10.0(lH,s) 0 實例31 溴化 H(2R,3R)-3-[4-(4-氰基-苯基）--塞唑-2-基]·2-(2,4-二氟-苯基）-2-羥基-丁基]-4-(3,5-二甲基-4-甲胺基乙醯氧基-芊基）-1Η-[1，2,4]三 唑-4-鐵鹽酸鹽 經濟部中央標準局員工消費合作社印製 藉由類似方法B中所述之程序，獲得溴化4-[4-[(第三-丁氧 羰基-甲基-胺基）乙醯氧基]-3,5-二甲基·芊基】-l-[(2R,3R)-3-[4-(4· 氰基-苯基）-嘍唑-2-基]-2·(2,4-二氟-苯基）-2-羥基-丁基]-1H-[1,2,4] ***-4-巍（1 : 1)。於4-{4-[(第三丁氧羰基甲基-胺基）-乙醯氧 基]-3,5-二曱基-芊基]-l-[(2R，3R)-3-[4-(4-氰基-苯基）-，塞唑-2-基]-2-(2,4-二氟-苯基）-2-羥基-丁基]-1Η-[1，2,4]***-4-鐵（1 : 1)(198.7 克 ，241毫莫耳）在EtOAc (1000毫升）中之溶液内，在室溫下添 加HC1於EtOAc (4N，600毫升）中之溶液，歷經30分鐘，並激 烈攪拌。將所形成之懸浮液於室溫下攪拌3小時。於玻璃 濾器（3G)上收集沈澱物，並以醚（500毫升X 10)洗滌，且在眞 空及40°C下乾燥2天，然後在80°C下乾燥12小時，而得溴化 1-[(2災!311)-3-[4-(4-氣基本基）-1*塞哇-2-基]-2-(2,4-二氣-苯基）-2-獲基- -_ 本紙張尺度適用中國國家橾準（CNS ) A4規格（210X2Q7公釐） 經濟部中央標準局員工消費合作社印製 41594? A7 * ____B7 五、發明説明（36 ) 丁基]-4-(3,5-二甲基-4-甲胺基乙醯氧基-苄基）-1Η-[1,2,4]***-4-鐵鹽酸鹽（183.3克，100% )，爲無色粉末。 物理形式：非晶質粉末；FAB-MS : m/z 643 (M-Br)+ ; 1H-NMR (DMSO-de) ό 1.18(3H,d,J=7.3Hz),2.12(6H,s),2.64(3H,s), 4.13(lH,q,J=7.3), 4.42(2H,s), 4.72(1 H,d,J=14.2), 5.01(lH,d,J=14.2), 5.39(2H,s), 6.70(lH,s), 6.90 -6.94(lH,m), 7.13(2H,m), 7.26-7.34(2Η,ιη), 7.94(2H}d,J=8.3), 8.20(2H,d,J=8.3), 8.44(lH,s), 9.07(m，s), 9.51(2H,寬廣 s), 10.17(lH,s)。 實例32 下列化合物可根據類似實例〗或9之方式製成： 溴化4-(4-乙醯氧基-3,5-二甲基苄基）-l-[(2R，3R)-2-(2,4-二氟苯 基）-2-羥基-3-{5-氧基-444-(2,2,3,3-四氟基丙氧基）苯基]-4,5-二氫-[1,2,4]***-1-基]丁基]·1Η·[1，2,4]***-4-巍， 溴化4-(4-乙醯氧基-3,5-二甲基苄基）-l-[(2R)-2-(2,4-二氟苯基）-2-羥基-3-甲基·3-(6·[1,2,4]***-1-基-嗒畊基-3-基對胺苯磺醯基） 丁基 ΗΗ-[1，2,4]***-4-巍， 溴化4-(4-乙醯氧基-3,5-二甲基苄基）-1-[(211)-2-(2,4-二氟苯基）· 2-羥基-3-(3-{(Ζ)-2·[4-(2,2,3,3-四氟基丙氧基）笨基]乙烯基1-[1,2,4] ***-1-基）丙基]_1Η-[1，2,4]***-4-攙， 溴化4-(4-乙醯氧基-3,5-二甲基-节基）-1-[(211，311)-2-(2,4-二氟苯 基）·2-羥基-3-甲烷磺醯基丁基]-1Η-[1，2,4]***-4-微， 溴化4-(4-乙醯氧基-3,5-二甲基苄基）-l-[(2R-順式）-2-(2,4-二氟 苯基）-4-[4-[4-[4-[l-[(lS，2S)-l-乙基-2-羥丙基）·5·氧基-1,5-二氫[1，2,4] ***-4-基]苯基]六氫吡畊-1-基]苯氧基甲基]四氫呋喃-2-基甲 基]-叫1，2,4]***， 本紙張尺度適用中國國家標準（CNS) Α4規格（210/13¾¾ ) (請先閱讀背面之注意事項再填寫本頁) ί % ,?τ 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（37 ) 溴化4-(4-乙醯氧基-3-甲基苄基）-l-[(2R-順式）-2-(2,4-二氟苯基 )_4-[4-[4-[4-[l-[(lS，2S)-l-乙基-2-經丙基)-5-氧基-1,5-二氫-[1，2,4]*** •4-基]苯基]六氫吡'•井-1-基]苯氧基甲基]四氫呋喃-2-基甲基]-1H-[1,2,4]*** 4-銳， 溴化4-(4-乙醯氧基苄基）-1-[(211-順式）-2-(2,4-二氟苯基）-4-[4-[4-[4-[l-[(lS，2S)-l-乙基-2-羥丙基）-5-氧基-1,5-二氫[1，2,4]***-4-基]苯 基]六氫吡畊基]苯氧基甲基]四氫呋喃-2-基甲基]-1H-[1,2,4] 三峻-4-鐵， 溴化4-(4-乙醯氧基-3,5-二氣苄基）-l-[(2R-順式）-2-(2,4-二氟苯 基）-4-[4-[4-[4-[l-[(lS，2S)-(l-乙基-2-羥丙基）]-5-氧基-1，5-二氫-[1，2,4] ***-4-基]苯基]六氫吡》井-1-基]苯氧基甲基]四氮呋喃-2-基甲 基]-1H-[1,2,4]***-4-銳， 溴化4-(4-乙醯氧基-3-氣基苄基）-l-[(2R-順式）-2-(2,4-二氟苯基 )-4-[4-[4-[4-[H(lS，2S)-l-乙基-2-羥丙基)-5-氧基-1，5-二氫-[1，2,4]*** -4-基]苯基]六氫吡畊-1-基]苯氧基甲基]四氫呋喃-2-基甲基]-1H-[1，2,4]*** 4-巍， 溴化4-(4-乙醯氧基-3-甲苄基）-l-[(2R，3R)-2-(2,4-二氟苯基）-2-羥 基-3-[4-(4-氰基苯基），塞唑-2-基]丁基]·1Η·[1二4]***-4-攙， 溴化4-(4-乙醯氧基芊基）-1-[(2尺,311)-2-(2,4-二氟苯基）-2-羥基-3-[4-(4-氰基苯基）嘧唑-2-基]丁基]-1Η-[1，2,4]***冬娩， 溴化4-(4-乙醯氧基-3,5-二氣芊基）-1-[(2民311)-2-(2,4-二氟苯基）-2-羥基-3-[4-(4-氰基苯基 >塞唑-2-基]丁基]-1Η-[1,2,4]***-4说， 溴化4-(4-乙醯氧基-3-氣基芊基)-1-[(211，311)-2~(2,4-二氟苯基）-2-羥基-3-[4-(4-氰基苯基 >塞唑-2-基]丁基]-1Η-[1,2,4]***-4-鐵， __ -40- _ 本紙張尺度適用中國國家標準（CNS ) Α4規格（21 Οχ 297公犛） n n fl·--«Τ— J n I— 1^1 I T /t- (請先閲讀背面之注意事項再填耗本頁) 415947 A7 4 __________ 五、發明説明（38 ) 溴化4-(4-乙醯氧基-3,5-二甲基苄基）-1-[2-羥基-3-甲基-3-甲基 鮮胺苯磺醯基-2·(4·三氟甲基苯基）丁基]-1H-[1,2,4]***>4-巍， 及 溴化4-(4-乙醯氧基-3,5-二甲基-亨基）-1-[[(5民611)-：2-甲氧亞胺 基-3,3-二甲基-6-[(4-三氟甲氧基苯氧基）甲基]環己基]甲基]-111-[1,2,4]***-4-纔。 實例A : 供肌内投藥用之無水安瓿瓶之製造： 以常用方法製備0.5克溴化4-(4-乙醯氧基-3,5-二曱基，芊基）-H[(lR,6R)-2-甲氧亞胺基-3,3-二甲基-6-[(4-三氟甲氧基苯氧基) 甲基]環己基]甲基]-1H-[1，2,4]***-4-歲之凍乾物，並填入安瓿 瓶中。於投藥之前，將凍乾物以2.5毫升2%利多卡因鹽酸 鹽溶液處理。 實例B : 以本質上習用之方式，製造各含有下列成份之硬明膠膠 囊： (請先閱讀背面之注$項再填寫本頁) 裝· 訂 經濟部中央標準局員工消費合作社印袋 溴化4-(4-乙醯氧基·3,5-二甲基-苄基）-1-[[(5艮61〇-2-甲氧亞胺基-3,3-二甲基-6-[(4-三氟 甲氧基苯氧基）甲基]環己基]甲基]-1H-[1，2,4] 三峻-4-鐵 乳糖 結晶性纖維素 砂酸，淡而無水 滑石 硬脂酸鎂 克克克克克克 毫毫毫毫毫毫 ο 6 o103 1 0 5 3 總計200毫克 本紙張尺度適用中國國家榡準（CNS ) .M規格（2!0X297公兑） ___-41 - 41594? A 7 B7 克克克克克克克 毫毫毫毫毫毫毫 0 0 0 0 6 3 1 0 6 2 1 五、發明説明（39 ) 實例C : 以本質上習用之方式，製造各含有下列成份之片劑 溴化4-(4-乙醯氧基-3,5-二甲基芊基）-1-[[(5R,6R)-2-甲氧亞胺基-3,3-二甲基-6-[(4-三氟 甲氧基苯氧基）甲基]環己基]甲基]-1H-[1，2,4] ***-4-龜 乳糖 玉米澱粉 澱粉羥基乙酸鈉 聚乙烯基四氫吡咯酮 滑石 硬脂酸鎂 總計200毫克 (讀先聞讀背面之注意事項再填寫本頁) 經濟部中央標準局負工消費合作社印掣 _-42- 本紙張尺度適用中國國家標準（（：?^)六4規格（210/ 297公釐）11T Printed by the Consumer Cooperatives of the Central Bureau of Economic Affairs of the Ministry of Economic Affairs 415947 A7 ____B7 V. Description of the invention (35) (Please read the precautions on the back before filling in this page hydroxybutyl 1-4- 丨 4-"(ethylamino) Acetyloxy 1-3,5-dimethylbenzyl 1-1H- 丨 1,2,41 triazole-4-trifluoroacetate; Physical form: white powder; FAB-MS: m / z 657 (M-Br) +; 1H-NMR (CD3OD) δ 1.25 (3H, d, J = 7.3Hz) i 1.38 (3H, U = 7.3Hz), 2.22 (6H, s), 3.22 (2H, q, J = 7.3Hz), 4.27 (1 H, q, J = 7.3Hz), 4.48 (2H, s), 4.67 (lH, d, J = 14.2Hz), 5.1 2 (lH, d, J = 14.2Hz), 5.35 (2H, s), 6.73-7.29 (3H ^ n), 7.15 (2H, s), 7.82 (2H, d, J = 8.6Hz), 8.10 (lH, s), 8.18 (2H, d, J = 8.6Hz), 8.75 (lH, s), 10.0 (lH, s) 0 Example 31 Brominated H (2R, 3R) -3- [4- (4-cyano-phenyl)-sepazole-2- Group] · 2- (2,4-difluoro-phenyl) -2-hydroxy-butyl] -4- (3,5-dimethyl-4-methylaminoethylethoxy-fluorenyl)- 1Η- [1,2,4] triazole-4-iron hydrochloride printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. Tri-butoxycarbonyl-methyl-amino) ethenyloxy] -3,5-dimethyl · fluorenyl] -l-[(2R, 3R) -3- [4- (4 · cyano-phenyl) -oxazol-2-yl] -2 · (2,4-difluoro-phenyl) -2-hydroxy-butyl] -1H- [1,2, 4] Triazole-4-pyrene (1: 1). In 4- {4-[(Third butoxycarbonylmethyl-amino) -acetamido] -3,5-diamidino-fluorenyl ] -l-[(2R, 3R) -3- [4- (4-cyano-phenyl)-, sedazol-2-yl] -2- (2,4-difluoro-phenyl) -2 -Hydroxy-butyl] -1Η- [1,2,4] triazole-4-iron (1: 1) (198.7 g, 241 mmol) in EtOAc (1000 ml) at room temperature Next, a solution of HC1 in EtOAc (4N, 600 ml) was added over 30 minutes and stirred vigorously. The resulting suspension was stirred at room temperature for 3 hours. The precipitate was collected on a glass filter (3G), and Ether (500 ml X 10) was washed and dried in air at 40 ° C for 2 days, and then dried at 80 ° C for 12 hours to obtain bromide 1-[(2hazard! 311) -3- [4- (4-Gas basic group) -1 * Sawa-2-yl] -2- (2,4-Digas-phenyl) -2-acyl- -_ This paper size applies to China National Standards (CNS) A4 specification (210X2Q7 mm) 41594 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 * ____B7 V. Description of the invention (36) Butyl] -4- (3,5-dimethyl 4-Methylaminoethylacetoxy-benzyl) -1H- [1,2,4] triazole-4-iron hydrochloride (183.3 g, 100%) is a colorless powder. Physical form: amorphous powder; FAB-MS: m / z 643 (M-Br) +; 1H-NMR (DMSO-de) ό 1.18 (3H, d, J = 7.3Hz), 2.12 (6H, s) , 2.64 (3H, s), 4.13 (lH, q, J = 7.3), 4.42 (2H, s), 4.72 (1 H, d, J = 14.2), 5.01 (lH, d, J = 14.2), 5.39 (2H, s), 6.70 (lH, s), 6.90 -6.94 (lH, m), 7.13 (2H, m), 7.26-7.34 (2Η, ιη), 7.94 (2H) d, J = 8.3), 8.20 (2H, d, J = 8.3), 8.44 (lH, s), 9.07 (m, s), 9.51 (2H, broad s), 10.17 (lH, s). Example 32 The following compounds can be prepared in a similar manner as in Example IX or 9: 4- (4-Ethyloxy-3,5-dimethylbenzyl) -l-[(2R, 3R) -2- (2,4-difluorophenyl) -2-hydroxy-3- {5-oxy-444- (2,2,3,3-tetrafluoropropoxy) phenyl] -4,5-di Hydrogen- [1,2,4] triazol-1-yl] butyl] · 1Η · [1,2,4] triazol-4-carbine, 4- (4-ethoxyloxy-3, bromide, 5-dimethylbenzyl) -l-[(2R) -2- (2,4-difluorophenyl) -2-hydroxy-3-methyl · 3- (6 · [1,2,4] Triazol-l-yl-dacrotyl-3-yl-p-aminobenzenesulfonyl) butylfluorene- [1,2,4] triazol-4-yl, 4- (4-ethylfluorenyl bromide) -3,5-dimethylbenzyl) -1-[(211) -2- (2,4-difluorophenyl) · 2-hydroxy-3- (3-{(Z) -2 · [4 -(2,2,3,3-tetrafluoropropoxy) benzyl] vinyl 1- [1,2,4] triazol-1-yl) propyl] _1Η- [1,2,4] Triazole-4-fluorene, 4- (4-acetamidooxy-3,5-dimethyl-benzyl) -1-[(211,311) -2- (2,4-difluorobenzene ) · 2-Hydroxy-3-methanesulfonylbutyl] -11- [1,2,4] triazole-4-micro, 4- (4-acetamidooxy-3,5-dibromide) Methylbenzyl) -l-[(2R-cis) -2- (2,4-difluorophenyl) -4- [4- [4- [4- [l-[(lS, 2S)- l-ethyl-2-hydroxypropyl) · 5 · oxy-1 , 5-dihydro [1,2,4] triazol-4-yl] phenyl] hexahydropyrine-1-yl] phenoxymethyl] tetrahydrofuran-2-ylmethyl] -called 1,2 , 4] Triazole, this paper size applies Chinese National Standard (CNS) Α4 specification (210 / 13¾¾) (Please read the precautions on the back before filling this page) ί% ,? τ Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Preparation of A7 B7 V. Description of the invention (37) 4- (4-Ethyloxy-3-methylbenzyl) bromide-l-[(2R-cis) -2- (2,4-difluorobenzene Group) _4- [4- [4- [4- [l-[(lS, 2S) -1-ethyl-2-transpropyl) -5-oxy-1,5-dihydro- [1, 2,4] triazole • 4-yl] phenyl] hexahydropyridine ′ • I-1-yl] phenoxymethyl] tetrahydrofuran-2-ylmethyl] -1H- [1,2,4] tri 4-Azole, 4- (4-Ethyloxybenzyl) bromide-1-[(211-cis) -2- (2,4-difluorophenyl) -4- [4- [4 -[4- [l-[(lS, 2S) -l-ethyl-2-hydroxypropyl) -5-oxy-1,5-dihydro [1,2,4] triazol-4-yl ] Phenyl] hexahydropyridyl] phenoxymethyl] tetrahydrofuran-2-ylmethyl] -1H- [1,2,4] sanjun-4-iron, 4- (4-acetamidine) bromide Oxy-3,5-diaminobenzyl) -l-[(2R-cis) -2- (2,4-difluorophenyl) -4- [4- [4- [4- [l- [(lS, 2S)-(l-ethyl-2-hydroxypropyl ] -5-oxy-1,5-dihydro- [1,2,4] triazol-4-yl] phenyl] hexahydropyridine >> I-1-yl] phenoxymethyl] tetraazafuran 2-ylmethyl] -1H- [1,2,4] triazol-4-rule, 4- (4-ethoxymethyl-3-aminobenzyl) -l-[(2R- Cis) -2- (2,4-difluorophenyl) -4- [4- [4- [4- [H (lS, 2S) -1-ethyl-2-hydroxypropyl) -5- Oxy-1,5-dihydro- [1,2,4] triazol-4-yl] phenyl] hexahydropyrine-1-yl] phenoxymethyl] tetrahydrofuran-2-ylmethyl] -1H- [1,2,4] triazole 4-pyridine, 4- (4-ethytoxy-3-methylbenzyl) bromide-l-[(2R, 3R) -2- (2,4 -Difluorophenyl) -2-hydroxy-3- [4- (4-cyanophenyl), sedazol-2-yl] butyl] · 1Η · [1 二 4] triazole-4- 搀, 4- (4-Ethoxyfluorenyl) bromide-1-[(2 feet, 311) -2- (2,4-difluorophenyl) -2-hydroxy-3- [4- (4- Cyanophenyl) pyrimazol-2-yl] butyl] -1 [-[1,2,4] triazole winter delivery, 4- (4-acetamidooxy-3,5-diaziridinyl bromide ) -1-[(2min 311) -2- (2,4-difluorophenyl) -2-hydroxy-3- [4- (4-cyanophenyl > sedazol-2-yl) butyl Group] -1Η- [1,2,4] triazole-4 said, 4- (4-ethoxyfluorenyl-3-aminomethyl) bromide-1-[(211,311) -2 ~ ( 2,4-difluorophenyl) -2-hydroxy-3- [4- (4-cyanophenyl) > Azole-2-yl] butyl] -1Η- [1,2,4] triazol-4-iron, __ -40- _ This paper size applies to China National Standard (CNS) A4 specification (21 〇χ 297 公 牦) nn fl ·-«Τ— J n I— 1 ^ 1 IT / t- (Please read the precautions on the back before filling in this page) 415947 A7 4 __________ V. Description of the invention (38) Bromide 4- (4 -Ethyloxy-3,5-dimethylbenzyl) -1- [2-hydroxy-3-methyl-3-methyl fresh amine benzylsulfonyl-2 · (4 · trifluoromethylbenzene ) Butyl] -1H- [1,2,4] triazole > 4-pyridine, and 4- (4-ethytoxy-3,5-dimethyl-henyl) -1-bromide [[(5Min 611)-: 2-methoxyimino-3,3-dimethyl-6-[(4-trifluoromethoxyphenoxy) methyl] cyclohexyl] methyl]- 111- [1,2,4] triazole-4-cai. Example A: Production of anhydrous ampoules for intramuscular administration: 0.5 g of 4- (4-ethoxyl-3,5-difluorenyl, fluorenyl) -H [(lR, 6R) -2-methoxyimino-3,3-dimethyl-6-[(4-trifluoromethoxyphenoxy) methyl] cyclohexyl] methyl] -1H- [1,2 4] Triazole-4-year-old lyophilisate and fill into ampoules. Prior to administration, the lyophilisate was treated with 2.5 ml of a 2% lidocaine hydrochloride solution. Example B: Manufacturing hard gelatin capsules each containing the following ingredients in a customary way: (Please read the note on the back before filling in this page) Binding and ordering brominated printed bags of employees ’cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 4 -(4-Ethyloxy · 3,5-dimethyl-benzyl) -1-[[(5gen61〇-2-methoxyimino-3,3-dimethyl-6- [ (4-Trifluoromethoxyphenoxy) methyl] cyclohexyl] methyl] -1H- [1,2,4] Sanjun-4-ferrolactose crystalline cellulose oxalic acid, light and anhydrous talc hard Magnesium stearate grams grams grams grams grams grams milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli milli mill ο 6 o103 1 0 5 3 total 200 milligrams of this paper standard applicable to China National Standards (CNS). M specifications (2! 0X297) ___- 41- 41594? A 7 B7 gram gram gram gram gram gram gram milligram milligram millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter millimeter 0 0 0 0 6 3 1 0 6 2 1 Tablets with the following ingredients: bromide 4- (4-ethoxymethyl-3,5-dimethylfluorenyl) -1-[[((5R, 6R) -2-methoxyimino-3,3- Dimethyl-6-[(4-trifluoromethoxyphenoxy) methyl] cyclohexyl] methyl] -1H- [1,2,4] triazole-4-galactose corn starch starch hydroxyethyl Sodium polyvinyltetrahydropyrrolidone talc magnesium stearate total 200 mg National standard ((:? ^) 6 4 specifications (210/297 mm)

Claims (1)

文專利修正二(88年丨2月)屋 ▼請專利範_ 88.12. 1 6，ι^ 年月 ΜText Patent Amendment II (88 丨 February) House ▼ Please Patent Fan_ 88.12. 1 6, ι ^ year Μ Π) 請 先 聞 其中 Q為式II唑化合物之其餘部份 0' •Q (II) 面 之 注 意 事 項 再 § 寫金、 本个 % I 其具有抗真菌活性； Z R1 與 R2 經濟部中央祿率局貝工消費合作社印製 3. 為氮或甲川； 各獨立為氫原子或_〇γ基團[其中Y 理學條件下易於水解之基圓]; R3與R4各獨立為氫或鹵原子、基、c 氧基、羧基或甲氧羰基；及 X' 為藥學上可接受之陰離子， 以及通式（I)化合物之鹽、水合物或溶劑合物》 根據申請專利範園第1項之化合物，其中易於水解之基 團Y為胺基酸之醯基殘基，或Y係R5 C0- ’其中R5為 氫、C ! _ 5烷氧基' C 5烷基，其可能視情況被羧基、 胺基、C i _ 5烷胺基 '吡啶基或苯基取代° 根據中請專利範圍第I項之化合物，其中 f Ζ·Ν — 0 4- Kir*-/ 為在生 烷 訂 本紙張尺度適用中國國家標準（CNS ) Ad说格（210X297公釐） 文專利修正二(88年丨2月)屋 ▼請專利範_ 88.12. 1 6，ι^ 年月 ΜΠ) Please note that Q is the rest of the compound of formula II azole 0 ′ • Note on Q (II), then write gold, this% I has antifungal activity; Z R1 and R2 Central Ministry of Economic Affairs Printed by the Bureau of Shellfish Consumer Cooperatives 3. Nitrogen or Jiachuan; each independently is a hydrogen atom or a _〇γ group [wherein the base circle is easy to hydrolyze under the conditions of Y]; each of R3 and R4 is independently a hydrogen or halogen atom, Group, coxy group, carboxyl group or methoxycarbonyl group; and X 'is a pharmaceutically acceptable anion, and a salt, hydrate or solvate of a compound of the general formula (I) "A compound according to item 1 of the patent application park , Where the easily hydrolyzable group Y is a fluorenyl residue of an amino acid, or Y is R5 C0- 'where R5 is hydrogen, C! _ 5 alkoxy' C 5 alkyl, which may be optionally carboxyl, Substituted by amine, C i _ 5 alkylamino 'pyridyl or phenyl ° According to the compound in the scope of the patent claim I, where f ZZ · N — 0 4- Kir *-/ Applicable to Chinese National Standards (CNS) Ad Grid (210X297 mm) Document Patent Amendment II (88 丨 Feb. 88) Fan _ 88.12. 1 6, ι ^ years Μ Π) 請 先 聞 其中 Q為式II唑化合物之其餘部份 0' •Q (II) 面 之 注 意 事 項 再 § 寫金、 本个 % I 其具有抗真菌活性； Z R1 與 R2 經濟部中央祿率局貝工消費合作社印製 3. 為氮或甲川； 各獨立為氫原子或_〇γ基團[其中Y 理學條件下易於水解之基圓]; R3與R4各獨立為氫或鹵原子、基、c 氧基、羧基或甲氧羰基；及 X' 為藥學上可接受之陰離子， 以及通式（I)化合物之鹽、水合物或溶劑合物》 根據申請專利範園第1項之化合物，其中易於水解之基 團Y為胺基酸之醯基殘基，或Y係R5 C0- ’其中R5為 氫、C ! _ 5烷氧基' C 5烷基，其可能視情況被羧基、 胺基、C i _ 5烷胺基 '吡啶基或苯基取代° 根據中請專利範圍第I項之化合物，其中 f Ζ·Ν — 0 4- Kir*-/ 為在生 烷 訂 本紙張尺度適用中國國家標準（CNS ) Ad说格（210X297公釐）Π) Please note that Q is the rest of the compound of formula II azole 0 ′ • Note on Q (II), then write gold, this% I has antifungal activity; Z R1 and R2 Central Ministry of Economic Affairs Printed by the Bureau of Shellfish Consumer Cooperatives 3. Nitrogen or Jiachuan; each independently is a hydrogen atom or a _〇γ group [wherein the base circle is easy to hydrolyze under the conditions of Y]; each of R3 and R4 is independently a hydrogen or halogen atom, Group, coxy group, carboxyl group or methoxycarbonyl group; and X 'is a pharmaceutically acceptable anion, and a salt, hydrate or solvate of a compound of the general formula (I) "A compound according to item 1 of the patent application park , Where the easily hydrolyzable group Y is a fluorenyl residue of an amino acid, or Y is R5 C0- 'where R5 is hydrogen, C! _ 5 alkoxy' C 5 alkyl, which may be optionally carboxyl, Substituted by amine, C i _ 5 alkylamino 'pyridyl or phenyl ° According to the compound in the scope of the patent claim I, where f ZZ · N — 0 4- Kir *-/ Applicable to Chinese National Standard (CNS) Ad Grid (210X297 mm) 415947 申請專利範圍 為種衍生自包括下列族群之峻化合物之基因： εΠ-1-[2·(2,4-二氣苯基峰似冷二氣苯基）甲氧基]乙基】-出- 味吐， d丨-順式-1-乙醯基_4_[4_[2_(2 4_二氣苯基）_2•(咪唑」·基甲 基）-1，3_二氧伍園+基]τ氧基]苯基]六氫吡畊， dI-2-[(RS)-第二-丁基]氣苯基）_2, (1Η丨，2,4_三嗤-1·基曱基）-1，3-二氧伍圜斗基]甲氧基]苯基]]_ 、氫Β比’基]苯基_3Η·[ι，2,4]三吐-3-1同， 2- [(lR，2R)-2-(2,4-二氣苯基）-2-#呈基-I-甲基-3-(1Η-1，2,4-三吐- 1-基）丙基]冰[4-(2,2,3,3_四氟基丙氧基）苯基]_3(2Η，4Η)_丨，2,4_三 峻g同， (+)-2-(2,4-—氟丰基）-3-甲基-1-(1H-1,2,4-三 σ坐-1-基）-3·(6·(1Η· 1’2,4-二吐-1-基）°备11井基-3-基硫基）丁 -2-醇， (2R)-2-(2,4-二氟苯基）-1-[3·[(ε)-4-(2,2,3,3-四氟基丙氧基）_笨 乙烯基]-(1又4-***-1-基）-3-(1，2,4-***-1-基）]丙-2-醇， dl-異赤If式-2-(2,4-二氟苯基）-3-甲基-績臨基2,4- ***-1-基）-丁 -2-醇， (-)-4W-[4-[[5，(2,4-二氟苯基）-5_(1Η-1，2,4-***-1-基甲基） 四氫呋喃-3-基]甲氧基]苯基]六氫吡"井基]苯基]-2-[(lS，2S)-l-乙基-2-¾丙基]-3H-1，2,4-三。坐-3-嗣， (2R，3R)-3-[4-(4-氰基苯基）噻唑-2-基）]-2-(2,4·二氟苯基）小 (1沁1，2,4-***小基）-丁-2-醇，- 3- 甲基-3-甲硫基小(1,2,4-***-1-基）-2-(三氟甲基苯基）-丁- -2- 本纸伕尺度適用中國國家揉準（(：阳）六4規^(210><297公釐） -- (請先閱讀背面之注事項再填寫本頁) 、1T 經涛部中央標隼局貞工消費合作社印製415947 The scope of the patent application is a gene derived from the compounds of the following groups: εΠ-1- [2 · (2,4-diphenylphenyl peak is like cold diphenylphenyl) methoxy] ethyl] -out -Weitu, d 丨 -cis-1-ethenyl_4_ [4_ [2_ (2 4_dioxophenyl) _2 • (imidazolyl · ylmethyl) -1,3_dioxin + Yl] τoxy] phenyl] hexahydropyridine, dI-2-[(RS) -second-butyl] aminophenyl) _2, (1Η 丨, 2,4_trisene-1 · yl · Group) -1,3-dioxolanyl] methoxy [phenyl]]] _, hydrogen B is more than 'yl] phenyl_3Η · [ι, 2,4] trito-3-1 same, 2-[(lR, 2R) -2- (2,4-difluorophenyl) -2- # presenting group-I-methyl-3- (1H-1,2,4-trisyl-1-yl ) Propyl] ice [4- (2,2,3,3_tetrafluoropropoxy) phenyl] _3 (2Η, 4Η) _ 丨, 2,4_Sanjun g, (+)-2 -(2,4-—fluorofungyl) -3-methyl-1- (1H-1,2,4-trisigma-1-yl) -3 · (6 · (1Η · 1'2,4 -Dithyl-1-yl) ° 11-yl-3-ylthio) but-2-ol, (2R) -2- (2,4-difluorophenyl) -1- [3 · [( ε) -4- (2,2,3,3-tetrafluoropropoxy) _benzylvinyl]-(1 and 4-triazol-1-yl) -3- (1,2,4-tri Azol-1-yl)] propan-2-ol, dl-isoerythrin If formula 2- (2,4- Difluorophenyl) -3-methyl-epiphenyl 2,4-triazol-1-yl) -but-2-ol, (-)-4W- [4-[[5, (2,4- Difluorophenyl) -5_ (1Η-1,2,4-triazol-1-ylmethyl) tetrahydrofuran-3-yl] methoxy] phenyl] hexahydropyridine " phenyl] phenyl]- 2-[(lS, 2S) -l-ethyl-2-¾propyl] -3H-1,2,4-tris. Zy-3- 嗣, (2R, 3R) -3- [4- (4-cyanophenyl) thiazol-2-yl)]-2- (2,4 · difluorophenyl) small (1qin1 , 2,4-triazole small group) -but-2-ol, 3-methyl-3-methylthio group small (1,2,4-triazol-1-yl) -2- (trifluoromethyl Phenyl) -Butyl- -2- The standard of this paper is applicable to Chinese national standard ((: yang) six 4 rules ^ (210 > < 297mm))-(Please read the notes on the back before filling this Page), 1T Printed by Zhengong Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs 415947 申請專利範圍 為種衍生自包括下列族群之峻化合物之基因： εΠ-1-[2·(2,4-二氣苯基峰似冷二氣苯基）甲氧基]乙基】-出- 味吐， d丨-順式-1-乙醯基_4_[4_[2_(2 4_二氣苯基）_2•(咪唑」·基甲 基）-1，3_二氧伍園+基]τ氧基]苯基]六氫吡畊， dI-2-[(RS)-第二-丁基]氣苯基）_2, (1Η丨，2,4_三嗤-1·基曱基）-1，3-二氧伍圜斗基]甲氧基]苯基]]_ 、氫Β比’基]苯基_3Η·[ι，2,4]三吐-3-1同， 2- [(lR，2R)-2-(2,4-二氣苯基）-2-#呈基-I-甲基-3-(1Η-1，2,4-三吐- 1-基）丙基]冰[4-(2,2,3,3_四氟基丙氧基）苯基]_3(2Η，4Η)_丨，2,4_三 峻g同， (+)-2-(2,4-—氟丰基）-3-甲基-1-(1H-1,2,4-三 σ坐-1-基）-3·(6·(1Η· 1’2,4-二吐-1-基）°备11井基-3-基硫基）丁 -2-醇， (2R)-2-(2,4-二氟苯基）-1-[3·[(ε)-4-(2,2,3,3-四氟基丙氧基）_笨 乙烯基]-(1又4-***-1-基）-3-(1，2,4-***-1-基）]丙-2-醇， dl-異赤If式-2-(2,4-二氟苯基）-3-甲基-績臨基2,4- ***-1-基）-丁 -2-醇， (-)-4W-[4-[[5，(2,4-二氟苯基）-5_(1Η-1，2,4-***-1-基甲基） 四氫呋喃-3-基]甲氧基]苯基]六氫吡"井基]苯基]-2-[(lS，2S)-l-乙基-2-¾丙基]-3H-1，2,4-三。坐-3-嗣， (2R，3R)-3-[4-(4-氰基苯基）噻唑-2-基）]-2-(2,4·二氟苯基）小 (1沁1，2,4-***小基）-丁-2-醇，- 3- 甲基-3-甲硫基小(1,2,4-***-1-基）-2-(三氟甲基苯基）-丁- -2- 本纸伕尺度適用中國國家揉準（(：阳）六4規^(210><297公釐） -- (請先閱讀背面之注事項再填寫本頁) 、1T 經涛部中央標隼局貞工消費合作社印製415947 The scope of the patent application is a gene derived from the compounds of the following groups: εΠ-1- [2 · (2,4-diphenylphenyl peak is like cold diphenylphenyl) methoxy] ethyl] -out -Weitu, d 丨 -cis-1-ethenyl_4_ [4_ [2_ (2 4_dioxophenyl) _2 • (imidazolyl · ylmethyl) -1,3_dioxin + Yl] τoxy] phenyl] hexahydropyridine, dI-2-[(RS) -second-butyl] aminophenyl) _2, (1Η 丨, 2,4_trisene-1 · yl · Group) -1,3-dioxolanyl] methoxy [phenyl]]] _, hydrogen B is more than 'yl] phenyl_3Η · [ι, 2,4] trito-3-1 same, 2-[(lR, 2R) -2- (2,4-difluorophenyl) -2- # presenting group-I-methyl-3- (1H-1,2,4-trisyl-1-yl ) Propyl] ice [4- (2,2,3,3_tetrafluoropropoxy) phenyl] _3 (2Η, 4Η) _ 丨, 2,4_Sanjun g, (+)-2 -(2,4-—fluorofungyl) -3-methyl-1- (1H-1,2,4-trisigma-1-yl) -3 · (6 · (1Η · 1'2,4 -Dithyl-1-yl) ° 11-yl-3-ylthio) but-2-ol, (2R) -2- (2,4-difluorophenyl) -1- [3 · [( ε) -4- (2,2,3,3-tetrafluoropropoxy) _benzylvinyl]-(1 and 4-triazol-1-yl) -3- (1,2,4-tri Azol-1-yl)] propan-2-ol, dl-isoerythrin If formula 2- (2,4- Difluorophenyl) -3-methyl-epiphenyl 2,4-triazol-1-yl) -but-2-ol, (-)-4W- [4-[[5, (2,4- Difluorophenyl) -5_ (1Η-1,2,4-triazol-1-ylmethyl) tetrahydrofuran-3-yl] methoxy] phenyl] hexahydropyridine " phenyl] phenyl]- 2-[(lS, 2S) -l-ethyl-2-¾propyl] -3H-1,2,4-tris. Zy-3- 嗣, (2R, 3R) -3- [4- (4-cyanophenyl) thiazol-2-yl)]-2- (2,4 · difluorophenyl) small (1qin1 , 2,4-triazole small group) -but-2-ol, 3-methyl-3-methylthio group small (1,2,4-triazol-1-yl) -2- (trifluoromethyl Phenyl) -Butyl- -2- The standard of this paper is applicable to Chinese national standard ((: yang) six 4 rules ^ (210 > < 297mm))-(Please read the notes on the back before filling this Page), 1T Printed by Zhengong Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs 415947 s* C8 -------- D8 、申請專利範圍 2-醇， 1-[[(丨R，2S，6R)-2-甲氧基_3,3·二甲基-6-(2-對-f苯基乙基）環 己基]-甲基]-丨|"1-[丨，2,4]三吐，及 (5R，6R)-2,2_二甲基-6_[(1Η_丨，2 4_***小基）甲基三氟 甲氧基）苯氧基]甲基]環己酮〇_甲基肟。 4.根據申請專利範圍第1項之化合物，其係選自包括： 溴化dl-l-(4-乙醯氧基_3,5-二曱基苄基）-3-[2-(2,4-二氣芊氧 基）-2-(2,4-二氣苯基）乙基]-3H-咪唑-1-， 溴化dl-l-(4-乙醯氧基-3-甲基莘基）_3_[2-(2,4-二氯芊氧基）-2-(2,4-.—鼠念、基）乙基]-3H-味 17全-1-， 溴化也-1-(4-乙醯氧基芊基）_3-[2-(2,4-二氣苄氧基）-2-(2,4-二 氣苯基）乙基j-3H-咪唑小 ， 溴化dl-l-(4_乙醯氧基芊基）-3-[(2R，4S)-4-[4-(4-乙醯基六氫 吡畊-1-基）苯氧基甲基]-2_(2,4-二氣苯基）_[丨，3]-二氧陸圜_2_ 基甲基]-3H-咪唑-1-， 溴化dl-l-(4-乙醯氧基-3,5-二甲基芊基）-34(211^)-4-14-(4-乙 酿基六氩吡畊-卜基）苯氧基甲基]-2-(2,4-二氣苯基）-[1，3]-二 氧陸園-2-基甲基]-3H-咪唑-1-， 溴化dl-I-(4-乙醯氧基-3-甲苄基）-3-[(2R,4S)-4-[4-(4-乙醯基 六氫吡畊-1-基）苯氧基甲基]-2-(2,4-二氣笨基）-[丨，3]-二氧陸 園-2-基甲基]-3H-咪唑-1-， 溴化dl-l-(4-乙醯氧基-3-甲氧基芊基）-3-[(：211，43>4-丨4-(4-乙 醯基六氫吡畊-1-基）苯氧基甲基]-2-(2,4-二氣苯基）-[1，3]-二 氧陸圜-2-基甲基]-3H-咪唑-1- ’ -3- 本紙乐尺度通用中國國家標準（CNS ) A4洗格（210X297公釐） (請先閲讀背面之注意事項再填寫本頁) 訂 經濟部中央榡嗥局貝工消費合作社印製415947 s * C8 -------- D8, patent application range 2-alcohol, 1-[[((R, 2S, 6R) -2-methoxy_3,3 · dimethyl-6- (2-p-fphenylethyl) cyclohexyl] -methyl]-丨 | " 1- [丨, 2,4] triple, and (5R, 6R) -2,2-dimethyl- 6 _ [(1Η_ 丨, 2 4-triazole small group) methyltrifluoromethoxy) phenoxy] methyl] cyclohexanone o-methyloxime. 4. The compound according to item 1 of the scope of patent application, which is selected from the group consisting of: bromide dl-l- (4-ethylamidooxy-3,5-difluorenylbenzyl) -3- [2- (2 , 4-Diaminofluorenyloxy) -2- (2,4-difluorophenyl) ethyl] -3H-imidazole-1-, bromide dl-1- (4-ethylfluorenyl-3-methyl Sulfonyl) _3_ [2- (2,4-dichlorofluorenyloxy) -2- (2,4 -.— rhamn, yl) ethyl] -3H-taste 17 all-1-, bromide also -1- (4-Acetyloxyfluorenyl) _3- [2- (2,4-digas benzyloxy) -2- (2,4-digas phenyl) ethyl j-3H-imidazole small , Bromide dl-l- (4-ethenyloxyfluorenyl) -3-[(2R, 4S) -4- [4- (4-ethenylhexahydropyridin-1-yl) phenoxy Methyl] -2_ (2,4-difluorophenyl) _ [丨, 3] -dioxolane_2_ylmethyl] -3H-imidazole-1-, bromated dl-l- (4-ethyl (Methoxy-3,5-dimethylfluorenyl) -34 (211 ^)-4-14- (4-Ethylhexylpyridine-butyl) phenoxymethyl] -2- (2 , 4-Dioxophenyl)-[1,3] -dioxolan-2-ylmethyl] -3H-imidazole-1-, bromide dl-I- (4-acetamidooxy-3- Methylbenzyl) -3-[(2R, 4S) -4- [4- (4-ethylfluorenylhexahydropyridine-1-yl) phenoxymethyl] -2- (2,4-digas (Benzyl)-[丨, 3] -Dioxolyl-2-ylmethyl] -3H-imidazole-1-, Brominated dl-l- (4-ethoxyfluorenyl-3-methoxyfluorenyl) -3-[(: 211,43 > 4- 丨 4- (4-ethenylhexahydropyridine-1- ) Phenoxymethyl] -2- (2,4-dioxophenyl)-[1,3] -dioxolan-2-ylmethyl] -3H-imidazole-1 -'- 3- The paper scale is in accordance with the Chinese National Standard (CNS) A4 (210X297 mm) (please read the precautions on the back before filling this page). Printed by the Central Government Bureau of the Ministry of Economic Affairs. 415947 s* C8 -------- D8 、申請專利範圍 2-醇， 1-[[(丨R，2S，6R)-2-甲氧基_3,3·二甲基-6-(2-對-f苯基乙基）環 己基]-甲基]-丨|"1-[丨，2,4]三吐，及 (5R，6R)-2,2_二甲基-6_[(1Η_丨，2 4_***小基）甲基三氟 甲氧基）苯氧基]甲基]環己酮〇_甲基肟。 4.根據申請專利範圍第1項之化合物，其係選自包括： 溴化dl-l-(4-乙醯氧基_3,5-二曱基苄基）-3-[2-(2,4-二氣芊氧 基）-2-(2,4-二氣苯基）乙基]-3H-咪唑-1-， 溴化dl-l-(4-乙醯氧基-3-甲基莘基）_3_[2-(2,4-二氯芊氧基）-2-(2,4-.—鼠念、基）乙基]-3H-味 17全-1-， 溴化也-1-(4-乙醯氧基芊基）_3-[2-(2,4-二氣苄氧基）-2-(2,4-二 氣苯基）乙基j-3H-咪唑小 ， 溴化dl-l-(4_乙醯氧基芊基）-3-[(2R，4S)-4-[4-(4-乙醯基六氫 吡畊-1-基）苯氧基甲基]-2_(2,4-二氣苯基）_[丨，3]-二氧陸圜_2_ 基甲基]-3H-咪唑-1-， 溴化dl-l-(4-乙醯氧基-3,5-二甲基芊基）-34(211^)-4-14-(4-乙 酿基六氩吡畊-卜基）苯氧基甲基]-2-(2,4-二氣苯基）-[1，3]-二 氧陸園-2-基甲基]-3H-咪唑-1-， 溴化dl-I-(4-乙醯氧基-3-甲苄基）-3-[(2R,4S)-4-[4-(4-乙醯基 六氫吡畊-1-基）苯氧基甲基]-2-(2,4-二氣笨基）-[丨，3]-二氧陸 園-2-基甲基]-3H-咪唑-1-， 溴化dl-l-(4-乙醯氧基-3-甲氧基芊基）-3-[(：211，43>4-丨4-(4-乙 醯基六氫吡畊-1-基）苯氧基甲基]-2-(2,4-二氣苯基）-[1，3]-二 氧陸圜-2-基甲基]-3H-咪唑-1- ’ -3- 本紙乐尺度通用中國國家標準（CNS ) A4洗格（210X297公釐） (請先閲讀背面之注意事項再填寫本頁) 訂 經濟部中央榡嗥局貝工消費合作社印製 415947 8 8 8 8 ABCD415947 s * C8 -------- D8, patent application range 2-alcohol, 1-[[((R, 2S, 6R) -2-methoxy_3,3 · dimethyl-6- (2-p-fphenylethyl) cyclohexyl] -methyl]-丨 | " 1- [丨, 2,4] triple, and (5R, 6R) -2,2-dimethyl- 6 _ [(1Η_ 丨, 2 4-triazole small group) methyltrifluoromethoxy) phenoxy] methyl] cyclohexanone o-methyloxime. 4. The compound according to item 1 of the scope of patent application, which is selected from the group consisting of: bromide dl-l- (4-ethylamidooxy-3,5-difluorenylbenzyl) -3- [2- (2 , 4-Diaminofluorenyloxy) -2- (2,4-difluorophenyl) ethyl] -3H-imidazole-1-, bromide dl-1- (4-ethylfluorenyl-3-methyl Sulfonyl) _3_ [2- (2,4-dichlorofluorenyloxy) -2- (2,4 -.— rhamn, yl) ethyl] -3H-taste 17 all-1-, bromide also -1- (4-Acetyloxyfluorenyl) _3- [2- (2,4-digas benzyloxy) -2- (2,4-digas phenyl) ethyl j-3H-imidazole small , Bromide dl-l- (4-ethenyloxyfluorenyl) -3-[(2R, 4S) -4- [4- (4-ethenylhexahydropyridin-1-yl) phenoxy Methyl] -2_ (2,4-difluorophenyl) _ [丨, 3] -dioxolane_2_ylmethyl] -3H-imidazole-1-, bromated dl-l- (4-ethyl (Methoxy-3,5-dimethylfluorenyl) -34 (211 ^)-4-14- (4-Ethylhexylpyridine-butyl) phenoxymethyl] -2- (2 , 4-Dioxophenyl)-[1,3] -dioxolan-2-ylmethyl] -3H-imidazole-1-, bromide dl-I- (4-acetamidooxy-3- Methylbenzyl) -3-[(2R, 4S) -4- [4- (4-ethylfluorenylhexahydropyridine-1-yl) phenoxymethyl] -2- (2,4-digas (Benzyl)-[丨, 3] -Dioxolyl-2-ylmethyl] -3H-imidazole-1-, Brominated dl-l- (4-ethoxyfluorenyl-3-methoxyfluorenyl) -3-[(: 211,43 > 4- 丨 4- (4-ethenylhexahydropyridine-1- ) Phenoxymethyl] -2- (2,4-dioxophenyl)-[1,3] -dioxolan-2-ylmethyl] -3H-imidazole-1 -'- 3- The paper scale is in accordance with the Chinese National Standard (CNS) A4 (210X297 mm) (Please read the precautions on the back before filling out this page). Ordered by the Central Bureau of the Ministry of Economic Affairs and printed by the Bayer Consumer Cooperative. 正 申請專利範園 /犬化dl-3-[(2R，4S)-4_[4-(4-乙疏基7T氫π比η井·丨-基）苯氧基甲 基]-2-(2,4--氣笨基）-[丨，3]-二氧陸園-2-基cp基]_丨_(4_異丁酷基 氧基-3,5-二甲基笮基）-3H-咪唑-1- 漠化dl-；3-[(2R，4S)-4-[4-(4-乙醯基六氫吡„井_丨_基）苯氧基甲 ]-2-(2,4-> —氣丰基）-[1,3]-二氧陸圜-2-基甲基]小(4_三曱基乙 醯基氧基-3,5-二甲基芊基）-3Η-咪唑-1-, 浪化（1丨-3-[(211，45)-4-[4-(4-乙.酷基六氫η比ρ井·卜基）苯氧基甲 基]-2-(2,4-一氣笨基）-[1，3]-二氧陸圜-2'基甲基]小[4-(2,2-二甲 基丙臨氧基）爷基]-3 H-咪哇-1-， >臭化(1丨-4-(4-苯甲酿氧基-3,5-二甲基苄基）_1_[4_[4_[4-[4-(1-(2-丁基-5-氧基-ls5-二氫[1,2,4]三嗅-4-基）苯基]六氩p比畊小基] 尽氧基曱基]-2-(2,4-二氯幂基）-[1，3]二氧伍圜_2·基甲基]-1H- [1,2,4]***-4-， 漠化 dl-4-[4-(〇比咬-3-羧基氧基）-3,5-二 T 基爷基]_ι_[4-[4-[4· [4-(1-(2-丁基_5·氧基-丨，5_二氫[1，2,4]三峻_4_基）苯基]六氫^比呼_ 1-基]苯氧基甲基]-:2-(2,4-二氯苯基）-[1，3]二氧伍園-2-基甲 基]-1土[1，2,4]三峻-4-， 經濟部中央祿车局貝工消費合作社印«. (請先閲讀背面之注^κ項再填窩本頁) 漠化 dl-4-(4-乙酿氧基-3,5-二甲基辛基）-i_[4_[4-[4-[4-[l-(2-丁 基-5-氡基-1，5-二氫[1，2,4]***-4-基）苯基]六氫吡畊-1-基]苯 氧基甲基]-2-(2,4-二氯苯基）-[1,3]二氧伍圜-2-基甲基]-1H-[1，2,4]三咬-4-， 溴化 dl-4-(4-乙醯氧基 _3-甲爷基）-1-[4-[4-[4-[4-[1-(2-丁基-5-氧基-1,5-二氫[1，2,4]***-4-基）苯基]六氫吡畊-1-基]苯氧基 甲基]-2-(2,4-二氯苯基）-Π，3]二氧伍園-2-基甲基]-1H-[1，2,4]三 -4- 本紙伕尺度通用中國國家梯準（CNS ) A4说格（210X2?7公釐） 415947 8 8 8 8 ABCDPatent pending Fanyuan / Kenhua dl-3-[(2R, 4S) -4_ [4- (4-Ethylthio 7T hydrogen π ratio η ·· -yl) phenoxymethyl] -2- ( 2,4--Gasbenzyl)-[丨, 3] -Dioxolyl-2-ylcpyl] _ 丨 _ (4_Isobutyloxy-3,5-dimethylfluorenyl) -3H-imidazole-1-desertification dl-; 3-[(2R, 4S) -4- [4- (4-ethylfluorenylhexahydropyridine WELL_ 丨 _YL) phenoxymethyl] -2- (2,4- > --Gafonyl)-[1,3] -dioxolan-2-ylmethyl] small (4-trimethylethylacetoxy-3,5-dimethyl Fluorenyl) -3Η-imidazole-1-, ionic (1 丨 -3-[(211,45) -4- [4- (4-eth. Methyl] -2- (2,4-monobenzyl)-[1,3] -dioxolane-2'ylmethyl] small [4- (2,2-dimethylpropylimoxy) ) Leeyl] -3 H-Miwa-1-, > Smell (1 丨 -4- (4-benzyloxy-3,5-dimethylbenzyl) _1_ [4_ [4_ [4 -[4- (1- (2-Butyl-5-oxy-ls5-dihydro [1,2,4] triol-4-yl) phenyl] hexagon p-Phenyl]] Fluorenyl] -2- (2,4-dichloromethylene)-[1,3] dioxofluoren-2-ylmethyl] -1H- [1,2,4] triazole-4-, Dl-4- [4- (〇 比比 -3-carboxyoxy) -3,5-diTylmethyl] _ι_ [4- [4- [4 · [4- (1- (2-butyl _5 · oxy- 丨, 5_dihydro [1,2,4] Sanjun_4_yl) phenyl] hexahydro ^ bihu_1-yl] phenoxymethyl]-: 2- (2,4-dichlorophenyl)-[1,3] dioxo-2-ylmethyl] -1 soil [1,2,4] Sanjun-4-, Ministry of Economic Affairs Industrial and consumer cooperative seal «. (Please read the note ^ κ on the back before filling in this page) Desertification dl-4- (4-Ethyloxy-3,5-dimethyloctyl) -i_ [4_ [4- [4- [4- [l- (2-butyl-5-fluorenyl-1,5-dihydro [1,2,4] triazol-4-yl) phenyl] hexahydropyridine -1-yl] phenoxymethyl] -2- (2,4-dichlorophenyl)-[1,3] dioxol-2-ylmethyl] -1H- [1,2,4 ] Tristetra-4-, bromide dl-4- (4-ethenyloxy-3-methylethyl) -1- [4- [4- [4- [4- [1- [2-butyl -5-oxy-1,5-dihydro [1,2,4] triazol-4-yl) phenyl] hexahydropyridin-1-yl] phenoxymethyl] -2- (2, 4-Dichlorophenyl) -Π, 3] dioxo-en-2-ylmethyl] -1H- [1,2,4] tri-4- This paper is commonly used in China National Standards (CNS) A4 Grid (210X2? 7mm) 415947 8 8 8 8 ABCD 正 申請專利範園 /犬化dl-3-[(2R，4S)-4_[4-(4-乙疏基7T氫π比η井·丨-基）苯氧基甲 基]-2-(2,4--氣笨基）-[丨，3]-二氧陸園-2-基cp基]_丨_(4_異丁酷基 氧基-3,5-二甲基笮基）-3H-咪唑-1- 漠化dl-；3-[(2R，4S)-4-[4-(4-乙醯基六氫吡„井_丨_基）苯氧基甲 ]-2-(2,4-> —氣丰基）-[1,3]-二氧陸圜-2-基甲基]小(4_三曱基乙 醯基氧基-3,5-二甲基芊基）-3Η-咪唑-1-, 浪化（1丨-3-[(211，45)-4-[4-(4-乙.酷基六氫η比ρ井·卜基）苯氧基甲 基]-2-(2,4-一氣笨基）-[1，3]-二氧陸圜-2'基甲基]小[4-(2,2-二甲 基丙臨氧基）爷基]-3 H-咪哇-1-， >臭化(1丨-4-(4-苯甲酿氧基-3,5-二甲基苄基）_1_[4_[4_[4-[4-(1-(2-丁基-5-氧基-ls5-二氫[1,2,4]三嗅-4-基）苯基]六氩p比畊小基] 尽氧基曱基]-2-(2,4-二氯幂基）-[1，3]二氧伍圜_2·基甲基]-1H- [1,2,4]***-4-， 漠化 dl-4-[4-(〇比咬-3-羧基氧基）-3,5-二 T 基爷基]_ι_[4-[4-[4· [4-(1-(2-丁基_5·氧基-丨，5_二氫[1，2,4]三峻_4_基）苯基]六氫^比呼_ 1-基]苯氧基甲基]-:2-(2,4-二氯苯基）-[1，3]二氧伍園-2-基甲 基]-1土[1，2,4]三峻-4-， 經濟部中央祿车局貝工消費合作社印«. (請先閲讀背面之注^κ項再填窩本頁) 漠化 dl-4-(4-乙酿氧基-3,5-二甲基辛基）-i_[4_[4-[4-[4-[l-(2-丁 基-5-氡基-1，5-二氫[1，2,4]***-4-基）苯基]六氫吡畊-1-基]苯 氧基甲基]-2-(2,4-二氯苯基）-[1,3]二氧伍圜-2-基甲基]-1H-[1，2,4]三咬-4-， 溴化 dl-4-(4-乙醯氧基 _3-甲爷基）-1-[4-[4-[4-[4-[1-(2-丁基-5-氧基-1,5-二氫[1，2,4]***-4-基）苯基]六氫吡畊-1-基]苯氧基 甲基]-2-(2,4-二氯苯基）-Π，3]二氧伍園-2-基甲基]-1H-[1，2,4]三 -4- 本紙伕尺度通用中國國家梯準（CNS ) A4说格（210X2?7公釐） 415947 A8 B8 C8 D8 六、申請專利範圍 哇-4- 溴化ί1Ι·4-(4-乙醯氧基芊基）小[4-[4-[4-[4-[1-(2-丁基-5-氧基_ 1,5-二氫[1，2,4]***-4-基）苯基]六氫吡畊-1-基]苯氧基甲基 2-(2,4-二氣苯基）-[],3]二氧伍圜-2-基甲基]-1Η-[1，2,4]***-4- 經濟部中央棹嗥局貝工消費合作社印装 甲烷磺酸 dM-[4-(4-{4-[4-(l-第二-丁基-5-氧基-1,5-二氫[1，2,4]. 三吐-4-基）苯基]-六氬比畊小基}苯氧基甲基）·2·(2,4-二氣_ 苯基）-[1，3]二氧伍園-2-基甲基]-4-(4-己醯氧基-3,5-二甲芊 基）-丨士[1，2,4]***-4-、， 溴化4-(4·乙醯氧基_3,5-二甲基芊基）-l-[(2R，3R)_2-(2,4-二氟 苯基）-2-羥基-3-{5-氧基-4-[4-(2,2,3,3-四氟基丙氧基）苯基]-4,5-二氫[1，2,4]***-i-基}丁基]_iH-[i，：2,4]三吐-4- ’ 溴化4-(4-乙醯氧基-3,5-二甲基芊基）-l-[(2R)-2-(2,4-二氟苯 基）-2-羥基-3-甲基-3-(641,2,4]***-1-基-塔-井基-3-基對胺苯 續驗基）丁基]-出-[1，2,4]三嗤-4-， 溴化4-(4-乙醯氧基-3,5-二甲基芊基）-l-[(2R)-2-(2,4-二氟苯 基）-2-羥基-3-(3-{闷-2-[4-(2,2,3,3-四氟基丙氧基）苯基]乙烯 基}-[1，2,4]***-1-基）丙基}-lH-[l，2,4]***-4-， 溴化4-(4-乙醯氧基-3,5-二甲基苄基）-l-[(2R,3R)-2-(2,4-二氟 苯基）-2-羥基-3-甲烷磺醯基丁基]2,4]***-4-， -溴化4-(4·乙醯氧基-3,5-二甲基苄基）-l-[(2R-順式）-2-(2,4-二 氟苯基）-4-[4-[4-[4-[l-[(lS，2S)-l-乙基-2-羥丙基）-5-氧基-1,5-二氫 -[1，2,4]三哇-4-基]苯基】六氫吡畊-1-基]苯氧基甲基]四氫啥 喃-2-基甲基]-1H-[1，2,4]***-4-， 本紙伕足度逍用中國國家棣準（CNS ) A4说格（2I0X297公釐） ^11 I : - --- m ^^^1 J .'=ί/< ^^^1 --'1 --- τ· 、-« (請先聞讀背面之注意事項再填寫本頁〕 415947 A8 B8 C8 D8 六、申請專利範圍 哇-4- 溴化ί1Ι·4-(4-乙醯氧基芊基）小[4-[4-[4-[4-[1-(2-丁基-5-氧基_ 1,5-二氫[1，2,4]***-4-基）苯基]六氫吡畊-1-基]苯氧基甲基 2-(2,4-二氣苯基）-[],3]二氧伍圜-2-基甲基]-1Η-[1，2,4]***-4- 經濟部中央棹嗥局貝工消費合作社印装 甲烷磺酸 dM-[4-(4-{4-[4-(l-第二-丁基-5-氧基-1,5-二氫[1，2,4]. 三吐-4-基）苯基]-六氬比畊小基}苯氧基甲基）·2·(2,4-二氣_ 苯基）-[1，3]二氧伍園-2-基甲基]-4-(4-己醯氧基-3,5-二甲芊 基）-丨士[1，2,4]***-4-、， 溴化4-(4·乙醯氧基_3,5-二甲基芊基）-l-[(2R，3R)_2-(2,4-二氟 苯基）-2-羥基-3-{5-氧基-4-[4-(2,2,3,3-四氟基丙氧基）苯基]-4,5-二氫[1，2,4]***-i-基}丁基]_iH-[i，：2,4]三吐-4- ’ 溴化4-(4-乙醯氧基-3,5-二甲基芊基）-l-[(2R)-2-(2,4-二氟苯 基）-2-羥基-3-甲基-3-(641,2,4]***-1-基-塔-井基-3-基對胺苯 續驗基）丁基]-出-[1，2,4]三嗤-4-， 溴化4-(4-乙醯氧基-3,5-二甲基芊基）-l-[(2R)-2-(2,4-二氟苯 基）-2-羥基-3-(3-{闷-2-[4-(2,2,3,3-四氟基丙氧基）苯基]乙烯 基}-[1，2,4]***-1-基）丙基}-lH-[l，2,4]***-4-， 溴化4-(4-乙醯氧基-3,5-二甲基苄基）-l-[(2R,3R)-2-(2,4-二氟 苯基）-2-羥基-3-甲烷磺醯基丁基]2,4]***-4-， -溴化4-(4·乙醯氧基-3,5-二甲基苄基）-l-[(2R-順式）-2-(2,4-二 氟苯基）-4-[4-[4-[4-[l-[(lS，2S)-l-乙基-2-羥丙基）-5-氧基-1,5-二氫 -[1，2,4]三哇-4-基]苯基】六氫吡畊-1-基]苯氧基甲基]四氫啥 喃-2-基甲基]-1H-[1，2,4]***-4-， 本紙伕足度逍用中國國家棣準（CNS ) A4说格（2I0X297公釐） ^11 I : - --- m ^^^1 J .'=ί/< ^^^1 --'1 --- τ· 、-« (請先聞讀背面之注意事項再填寫本頁〕 415947 Α8 B8>> 蹯8,12· Ι6；：:·ϊΐ 經濟部中央榡嗥局舅工消費合作社印11 夂'申請專利範圍 溴化4-(4-乙醯氧基-3-甲笮基）_1_[(2尺-順式）-2-(2,4-二氟苯 基）-4-[4-[4-[4-[I-[(lS，2S)-l-乙基-2-羥丙基）-5-氧基-1，5-二氫[1，2,4] 三峰_4·基]苯基]六氫吡》井-丨_基体氧基甲基]四氫呋喃_2_基 甲基]-出-[1，2,4]***-4-， 溴化4-(4-乙醯氧基苄基）-i-[(2R-順式）-2-(2,4-二氟苯基）-4-[4-[4-[4-[l-[(lS，2S)-l-乙基-2-超丙基）-5-氧基-1，5·二氫[1,2,4]三咬 -4-基]苯基]六氫吡。井-I-基]苯氧基甲基]四氫呋喃_2_基甲 基]-出-[1,2,4]三峻-4-， 溴化4-(4-乙醯氧基二氣苄基）-i_[(2R-順式）-2-(2,4-二氟 麥基）-4-[4-[4-[4-[I-[(lS，2S)-l-乙基-2-經丙基）-5-氧基-1,5-二氛 [1，2,4]***-4-基]苯基]六氫吡啩-1-基]苯氧基甲基]四氫吱喃 -2-基甲基]-1H-[1，2,4]***-4-， 溴化4-(4-乙醯氧基-3-氣芊基）-l-[(2R-順式）-2-(2,4-二氟苯 基）-4-[4-[4-[4-[l-[(lS，2S)-K 乙基-2-羥丙基）]-5-氧基-1,5-二氫 [1，2,4】三也-4-基]苯基]六氫峨畊·1-基]苯氧基甲基]四氫咬喃 -2-基甲基]-1Η-[ 1,2,4]三哇-4-， 溴化4_(4·乙醯氧基·3,5·二甲基芊基）-l-[(2R，3R)_2-(2,4-二氟 苯基）-2-羥基-3-[4-(4-氰基苯基）噻唑-2·基]丁基]-1H-[1，2,4]三 吨 _4_ ， 溴化4-(4-乙醯氧基-3-甲芊基）-l-[(2R，3R)-2-(2,4-二氟苯基）- 2-羥基-3-[4-(4-氰基苯基）噻唑-2-基]丁基]-出-[〖,2,4]***斗 ? 溴化4-(4-乙醯氧基苄基）-l-[(2R，3R)-2-(2,4-二氟苯基）-2-羥 基-3-[4-(4-氰基苯基 >塞唑-2-基]丁基]-1H-[1，2,4]***·4·， -6- 本紙張尺度適用中國囷家梯準（CNS ) Α4现格（210X297公釐） (請先聞请背面之注意事項再填爲本頁) 11Τ 415947 Α8 B8>> 蹯8,12· Ι6；：:·ϊΐ 經濟部中央榡嗥局舅工消費合作社印11 夂'申請專利範圍 溴化4-(4-乙醯氧基-3-甲笮基）_1_[(2尺-順式）-2-(2,4-二氟苯 基）-4-[4-[4-[4-[I-[(lS，2S)-l-乙基-2-羥丙基）-5-氧基-1，5-二氫[1，2,4] 三峰_4·基]苯基]六氫吡》井-丨_基体氧基甲基]四氫呋喃_2_基 甲基]-出-[1，2,4]***-4-， 溴化4-(4-乙醯氧基苄基）-i-[(2R-順式）-2-(2,4-二氟苯基）-4-[4-[4-[4-[l-[(lS，2S)-l-乙基-2-超丙基）-5-氧基-1，5·二氫[1,2,4]三咬 -4-基]苯基]六氫吡。井-I-基]苯氧基甲基]四氫呋喃_2_基甲 基]-出-[1,2,4]三峻-4-， 溴化4-(4-乙醯氧基二氣苄基）-i_[(2R-順式）-2-(2,4-二氟 麥基）-4-[4-[4-[4-[I-[(lS，2S)-l-乙基-2-經丙基）-5-氧基-1,5-二氛 [1，2,4]***-4-基]苯基]六氫吡啩-1-基]苯氧基甲基]四氫吱喃 -2-基甲基]-1H-[1，2,4]***-4-， 溴化4-(4-乙醯氧基-3-氣芊基）-l-[(2R-順式）-2-(2,4-二氟苯 基）-4-[4-[4-[4-[l-[(lS，2S)-K 乙基-2-羥丙基）]-5-氧基-1,5-二氫 [1，2,4】三也-4-基]苯基]六氫峨畊·1-基]苯氧基甲基]四氫咬喃 -2-基甲基]-1Η-[ 1,2,4]三哇-4-， 溴化4_(4·乙醯氧基·3,5·二甲基芊基）-l-[(2R，3R)_2-(2,4-二氟 苯基）-2-羥基-3-[4-(4-氰基苯基）噻唑-2·基]丁基]-1H-[1，2,4]三 吨 _4_ ， 溴化4-(4-乙醯氧基-3-甲芊基）-l-[(2R，3R)-2-(2,4-二氟苯基）- 2-羥基-3-[4-(4-氰基苯基）噻唑-2-基]丁基]-出-[〖,2,4]***斗 ? 溴化4-(4-乙醯氧基苄基）-l-[(2R，3R)-2-(2,4-二氟苯基）-2-羥 基-3-[4-(4-氰基苯基 >塞唑-2-基]丁基]-1H-[1，2,4]***·4·， -6- 本紙張尺度適用中國囷家梯準（CNS ) Α4现格（210X297公釐） (請先聞请背面之注意事項再填爲本頁) 11Τ 415947 A8 B8 C8 D8 年 月Ft 信正 88.12.16 經濟部中央標準局負工消費合作社印衷 六、申請專利範圍 >臭化4-(4-乙酿氧基-3,5-二氯苄基）小[(2R，3R)_2_(2 4_二氟苯 基）-2七基-3K4-氰基苯基）B塞唑j·基]丁基]_出[丨，2,4]三吐_ 4- ， /臭化4-(4-乙酿氧基-3-氣卞基）-丨_[(2|^3民)-2-(2,4-二氟苯基）· 2_控基-3-[4-(4-氰基苯基）魂唑_2_基]丁基]丨叫丨，2，#]***_4_ 漠化4-(4-乙醯氧基-3,5-二甲基苄基）小&羥基_3_甲基·3_ 甲基對胺苯項臨基-2-(4-三氟甲基苯基）丁基】_1Η_[ι，2,4]三嗤 -4- ； >臭化4-(4-乙疏氧基-3,5-二甲基芊基）小[[(5R，6R)_2_甲氧亞 胺基-3,3-二甲基-6-[(4-三氟甲氧基苯氧基）甲基]環己基]甲 基]-出-[1，2,4]***-4_ ，及 邊化4-(4-乙臨氧基-3,5-二甲基苄基）_丨_[(丨R，2S，6R)_2_甲氧 基-3,3-二甲基-6-(2-對-甲苯基乙基）環己基甲基]-丨叫口川三 嗅-4- 〇 5.根據申清專利紅圍弟1項之化合物，其係選自包括： >臭化（2R,3R)-4-(4-胺基乙醯氧基-2-羧基芊基）·卜[3_[4-(4-氰 基-苯基）-〇塞峻-2-基]-2-(2,4-二氟苯基）_2-短基丁基]_ιη-[1，2,4] ***-4· 三氟醋酸鹽， 邊化 I-[(2R，3R)-3-[4-(4-氰基苯基）-〇塞峻 _2_基]·2_(2,4-二氟苯 基）-2-經基丁基]-4-[(S)-3,5-二甲基-4-(四氫吡咯_2_羰基氧基）· 芊基]-1H-[1，2,4]***-4-三氟醋酸鹽， ί臭化（21^311)-4-(4-胺基乙酷氧基_3,5_二甲基罕基）小[3_[4_ (4-氰基苯基）-»塞峻-2-基]-2-(2,4-二氟苯基）_2_經基丁基]-1Η- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） -- (請先W讀背面之注意事項再填爲本頁) --° 415947 A8 B8 C8 D8 年 月Ft 信正 88.12.16 經濟部中央標準局負工消費合作社印衷 六、申請專利範圍 >臭化4-(4-乙酿氧基-3,5-二氯苄基）小[(2R，3R)_2_(2 4_二氟苯 基）-2七基-3K4-氰基苯基）B塞唑j·基]丁基]_出[丨，2,4]三吐_ 4- ， /臭化4-(4-乙酿氧基-3-氣卞基）-丨_[(2|^3民)-2-(2,4-二氟苯基）· 2_控基-3-[4-(4-氰基苯基）魂唑_2_基]丁基]丨叫丨，2，#]***_4_ 漠化4-(4-乙醯氧基-3,5-二甲基苄基）小&羥基_3_甲基·3_ 甲基對胺苯項臨基-2-(4-三氟甲基苯基）丁基】_1Η_[ι，2,4]三嗤 -4- ； >臭化4-(4-乙疏氧基-3,5-二甲基芊基）小[[(5R，6R)_2_甲氧亞 胺基-3,3-二甲基-6-[(4-三氟甲氧基苯氧基）甲基]環己基]甲 基]-出-[1，2,4]***-4_ ，及 邊化4-(4-乙臨氧基-3,5-二甲基苄基）_丨_[(丨R，2S，6R)_2_甲氧 基-3,3-二甲基-6-(2-對-甲苯基乙基）環己基甲基]-丨叫口川三 嗅-4- 〇 5.根據申清專利紅圍弟1項之化合物，其係選自包括： >臭化（2R,3R)-4-(4-胺基乙醯氧基-2-羧基芊基）·卜[3_[4-(4-氰 基-苯基）-〇塞峻-2-基]-2-(2,4-二氟苯基）_2-短基丁基]_ιη-[1，2,4] ***-4· 三氟醋酸鹽， 邊化 I-[(2R，3R)-3-[4-(4-氰基苯基）-〇塞峻 _2_基]·2_(2,4-二氟苯 基）-2-經基丁基]-4-[(S)-3,5-二甲基-4-(四氫吡咯_2_羰基氧基）· 芊基]-1H-[1，2,4]***-4-三氟醋酸鹽， ί臭化（21^311)-4-(4-胺基乙酷氧基_3,5_二甲基罕基）小[3_[4_ (4-氰基苯基）-»塞峻-2-基]-2-(2,4-二氟苯基）_2_經基丁基]-1Η- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） -- (請先W讀背面之注意事項再填爲本頁) --° C8i 年；'j : 乂 :1ΐδ ir. 經濟部中央橾準局貝工消費合作社印製 申請專利範圍 [1，2,4]***-4-三氟醋酸鹽， /臭化（2R，3R)-4-[4-(3-胺基丙酿氧基）_3,5_二甲基笮基]! [4 [4-(4-氰基苯基）-p塞唑_2_基]-2-(2,4-二氟苯基）_2_羥基，3·甲基丁 基]-出-[1,2,4]***-4·三氟醋酸鹽， /臭化（2R，3R)-4-[4-(4-胺基-丁酿氧基）_3,5-二甲基节基]^ [4-(4-氰基苯基）-噻唑_2-基]-2-(2,4-二氟苯基）_2-羥基-3_甲基丁 基]-1H-[I，2,4]***_4_三氟醋酸鹽，， 溴化（211，311)-4-[4-[[2-(胺基乙酿基）胺基]乙酿氧基]_35_ 甲基¥基]-l-[3-[4-(4-氰基苯基）塞峻_2·基]_2_(234-二氣苯基） 2-羥基-丁基]-1H-[1，2,4]***_4_三氟醋酸鹽， 漢化 l-[(2R，3R)-3-[4-(4-氰基苯基）-B塞峻·2·基]_2-(2,4_二氣苯 基）-2·經基丁基]-4-[4-[(S)-2,5-二胺基戊醯氧基]_3,5_二甲基·平 基]-1Η-[1，2,4]***-4-三氟醋酸鹽， 溴化4-[4-[(S)-2-胺基-丙醯氧基）_3,5-二甲基等基]i [(2R，3R)-3-[4-(4-氰基苯基）-魂唑冬基]-2·(2,4·二氟苯基峰題基 -丁基]-1Η-[1，2,4]***-4- 三氟醋酸鹽， 溴化H(2R，3R)-H4-(4-氰基苯基）-嘍唑-2-基]_2_(2,4·二氟苯 基）-2_短基丁基H-J3,5-二甲棊冰[(甲胺基）乙酿氧基]爷基]_ 1Η-[1，2,4]***-4- 三氟醋酸鹽， 溴化（2ί^3ΙΙ)-Η3-[4-(4-氰基苯基）-<塞唑 _2_基]_2-(2,4_二氟笨 基）-2-羥基丁基]-4-[3,5-二甲基-4-[(丙基胺基）乙醯氧基]苄 基]-1H-[1,2,4]***-4- 三氟醋酸鹽， 漠化 1-[(2ΐ^3Κ〇-3-[4-(4-氛基苯基）-嚷吐-2-基]-2-(2,4-二氟苯 基）_2_羥基丁基]-4-[4-[(S)_2-(曱胺基）丙醯氧基]-3允二甲基-亨 -8- 本纸張尺度逍用中國國家標率（CNS ) A4規格（210X297公釐） (請先聞讀背面之注意事項再填{4本頁} '袈· .訂 C8i 年；'j : 乂 :1ΐδ ir. 經濟部中央橾準局貝工消費合作社印製 申請專利範圍 [1，2,4]***-4-三氟醋酸鹽， /臭化（2R，3R)-4-[4-(3-胺基丙酿氧基）_3,5_二甲基笮基]! [4 [4-(4-氰基苯基）-p塞唑_2_基]-2-(2,4-二氟苯基）_2_羥基，3·甲基丁 基]-出-[1,2,4]***-4·三氟醋酸鹽， /臭化（2R，3R)-4-[4-(4-胺基-丁酿氧基）_3,5-二甲基节基]^ [4-(4-氰基苯基）-噻唑_2-基]-2-(2,4-二氟苯基）_2-羥基-3_甲基丁 基]-1H-[I，2,4]***_4_三氟醋酸鹽，， 溴化（211，311)-4-[4-[[2-(胺基乙酿基）胺基]乙酿氧基]_35_ 甲基¥基]-l-[3-[4-(4-氰基苯基）塞峻_2·基]_2_(234-二氣苯基） 2-羥基-丁基]-1H-[1，2,4]***_4_三氟醋酸鹽， 漢化 l-[(2R，3R)-3-[4-(4-氰基苯基）-B塞峻·2·基]_2-(2,4_二氣苯 基）-2·經基丁基]-4-[4-[(S)-2,5-二胺基戊醯氧基]_3,5_二甲基·平 基]-1Η-[1，2,4]***-4-三氟醋酸鹽， 溴化4-[4-[(S)-2-胺基-丙醯氧基）_3,5-二甲基等基]i [(2R，3R)-3-[4-(4-氰基苯基）-魂唑冬基]-2·(2,4·二氟苯基峰題基 -丁基]-1Η-[1，2,4]***-4- 三氟醋酸鹽， 溴化H(2R，3R)-H4-(4-氰基苯基）-嘍唑-2-基]_2_(2,4·二氟苯 基）-2_短基丁基H-J3,5-二甲棊冰[(甲胺基）乙酿氧基]爷基]_ 1Η-[1，2,4]***-4- 三氟醋酸鹽， 溴化（2ί^3ΙΙ)-Η3-[4-(4-氰基苯基）-<塞唑 _2_基]_2-(2,4_二氟笨 基）-2-羥基丁基]-4-[3,5-二甲基-4-[(丙基胺基）乙醯氧基]苄 基]-1H-[1,2,4]***-4- 三氟醋酸鹽， 漠化 1-[(2ΐ^3Κ〇-3-[4-(4-氛基苯基）-嚷吐-2-基]-2-(2,4-二氟苯 基）_2_羥基丁基]-4-[4-[(S)_2-(曱胺基）丙醯氧基]-3允二甲基-亨 -8- 本纸張尺度逍用中國國家標率（CNS ) A4規格（210X297公釐） (請先聞讀背面之注意事項再填{4本頁} '袈· .訂Patent pending Fanyuan / Kenhua dl-3-[(2R, 4S) -4_ [4- (4-Ethylthio 7T hydrogen π ratio η ·· -yl) phenoxymethyl] -2- ( 2,4--Gasbenzyl)-[丨, 3] -Dioxolyl-2-ylcpyl] _ 丨 _ (4_Isobutyloxy-3,5-dimethylfluorenyl) -3H-imidazole-1-desertification dl-; 3-[(2R, 4S) -4- [4- (4-ethylfluorenylhexahydropyridine WELL_ 丨 _YL) phenoxymethyl] -2- (2,4- > --Gafonyl)-[1,3] -dioxolan-2-ylmethyl] small (4-trimethylethylacetoxy-3,5-dimethyl Fluorenyl) -3Η-imidazole-1-, ionic (1 丨 -3-[(211,45) -4- [4- (4-eth. Methyl] -2- (2,4-monobenzyl)-[1,3] -dioxolane-2'ylmethyl] small [4- (2,2-dimethylpropylimoxy) ) Leeyl] -3 H-Miwa-1-, > Smell (1 丨 -4- (4-benzyloxy-3,5-dimethylbenzyl) _1_ [4_ [4_ [4 -[4- (1- (2-Butyl-5-oxy-ls5-dihydro [1,2,4] triol-4-yl) phenyl] hexagon p-Phenyl]] Fluorenyl] -2- (2,4-dichloromethylene)-[1,3] dioxofluoren-2-ylmethyl] -1H- [1,2,4] triazole-4-, Dl-4- [4- (〇 比比 -3-carboxyoxy) -3,5-diTylmethyl] _ι_ [4- [4- [4 · [4- (1- (2-butyl _5 · oxy- 丨, 5_dihydro [1,2,4] Sanjun_4_yl) phenyl] hexahydro ^ bihu_1-yl] phenoxymethyl]-: 2- (2,4-dichlorophenyl)-[1,3] dioxo-2-ylmethyl] -1 soil [1,2,4] Sanjun-4-, Ministry of Economic Affairs Industrial and consumer cooperative seal «. (Please read the note ^ κ on the back before filling in this page) Desertification dl-4- (4-Ethyloxy-3,5-dimethyloctyl) -i_ [4_ [4- [4- [4- [l- (2-butyl-5-fluorenyl-1,5-dihydro [1,2,4] triazol-4-yl) phenyl] hexahydropyridine -1-yl] phenoxymethyl] -2- (2,4-dichlorophenyl)-[1,3] dioxol-2-ylmethyl] -1H- [1,2,4 ] Tristetra-4-, bromide dl-4- (4-ethenyloxy-3-methylethyl) -1- [4- [4- [4- [4- [1- [2-butyl -5-oxy-1,5-dihydro [1,2,4] triazol-4-yl) phenyl] hexahydropyridin-1-yl] phenoxymethyl] -2- (2, 4-Dichlorophenyl) -Π, 3] dioxo-en-2-ylmethyl] -1H- [1,2,4] tri-4- This paper is commonly used in China National Standards (CNS) A4 Grid (210X2 ~ 7mm) 415947 A8 B8 C8 D8 VI. Application for patent scope Wow-4- bromide ί1Ι · 4- (4-ethoxyfluorenyl) small [4- [4- [4- [4 -[1- (2-butyl-5-oxy_ 1,5-dihydro [1,2,4] tri -4-yl) phenyl] hexahydropyrine-1-yl] phenoxymethyl 2- (2,4-difluorophenyl)-[], 3] dioxol-2-ylmethyl ] -1Η- [1,2,4] triazole-4- Printed methanesulfonic acid dM- [4- (4- {4- [4- (l-second -Butyl-5-oxy-1,5-dihydro [1,2,4]. Trisyl-4-yl) phenyl] -hexahydropyridine} phenoxymethyl) · 2 · (2,4-Digas_phenyl)-[1,3] dioxo-2-ylmethyl] -4- (4-hexyloxy-3,5-dimethylmethyl)-丨[1,2,4] triazol-4- ,, 4- (4 · ethylacetoxy-3,5-dimethylfluorenyl) -l-[(2R, 3R) _2- (2 , 4-difluorophenyl) -2-hydroxy-3- {5-oxy-4- [4- (2,2,3,3-tetrafluoropropoxy) phenyl] -4,5- Dihydro [1,2,4] triazol-i-yl} butyl] _iH- [i,: 2,4] tritul-4-'bromide 4- (4-acetamyloxy-3,5 -Dimethylfluorenyl) -l-[(2R) -2- (2,4-difluorophenyl) -2-hydroxy-3-methyl-3- (641,2,4] triazole-1 -Yl-tower-wellyl-3-yl p-aminobenzene continyl) butyl] -exo- [1,2,4] triamidine-4-, 4- (4-acetamyloxy-3) bromide , 5-dimethylfluorenyl) -l-[(2R) -2- (2,4-difluorophenyl) -2-hydroxy-3- (3-{{-2- [4- (2, 2,3,3-tetrafluoropropoxy) phenyl ] Vinyl}-[1,2,4] triazol-1-yl) propyl} -lH- [l, 2,4] triazol-4-, 4- (4-acetamido bromide- 3,5-dimethylbenzyl) -l-[(2R, 3R) -2- (2,4-difluorophenyl) -2-hydroxy-3-methanesulfonylbutyl] 2,4] Triazole-4-, -bromide 4- (4 · ethytoxy-3,5-dimethylbenzyl) -l-[(2R-cis) -2- (2,4-difluorobenzene ) -4- [4- [4- [4- [l-[(lS, 2S) -1-ethyl-2-hydroxypropyl) -5-oxy-1,5-dihydro- [1 , 2,4] trival-4-yl] phenyl] hexahydropyridin-1-yl] phenoxymethyl] tetrahydroxan-2-ylmethyl] -1H- [1,2,4 ] Triazole-4-, this paper is fully used in Chinese National Standards (CNS) A4 (2I0X297mm) ^ 11 I:---- m ^^^ 1 J. '= Ί / < ^ ^^ 1-'1 --- τ ·,-«(Please read the precautions on the back before filling in this page) 415947 A8 B8 C8 D8 VI. Application scope Wow-4- bromide 1Ι · 4- ( 4-Ethoxyfluorenyl) small [4- [4- [4- [4- [1- [2-butyl-5-oxy_ 1,5-dihydro [1,2,4] tri Azol-4-yl) phenyl] hexahydropyrine-1-yl] phenoxymethyl 2- (2,4-difluorophenyl)-[], 3] dioxol-2-ylmethyl Base] -1Η- [1,2,4] triazol-4-The consumption of shellfish by the Central Bureau of Economic Affairs of the Ministry of Economic Affairs The company printed methanesulfonic acid dM- [4- (4- {4- [4- (l-second-butyl-5-oxy-1,5-dihydro [1,2,4]. -4-yl) phenyl] -hexahydropyrene small group} phenoxymethyl) · 2 · (2,4-digas_phenyl)-[1,3] dioxolin-2-yl Methyl] -4- (4-hexamethyleneoxy-3,5-dimethylmethyl)-[1,2,4] triazole-4- ,, 4- (4 · ethylacetoxy bromide -3,5-dimethylfluorenyl) -l-[(2R, 3R) _2- (2,4-difluorophenyl) -2-hydroxy-3- {5-oxy-4- [4 -(2,2,3,3-tetrafluoropropoxy) phenyl] -4,5-dihydro [1,2,4] triazole-i-yl} butyl] _iH- [i ,: 2,4] trimethyl-4-'bromo 4- (4-ethoxyfluorenyl-3,5-dimethylfluorenyl) -l-[(2R) -2- (2,4-difluorobenzene (Yl) -2-hydroxy-3-methyl-3- (641,2,4) triazol-1-yl-tower-syl-3-yl p-aminophenyl continyl) butyl] -exo- [ 1,2,4] trifluoren-4-, 4- (4-ethoxyfluorenyl-3,5-dimethylfluorenyl) -l-[(2R) -2- (2,4-di Fluorophenyl) -2-hydroxy-3- (3- {suppressed-2- [4- (2,2,3,3-tetrafluoropropoxy) phenyl] vinyl}-[1,2, 4] triazol-1-yl) propyl} -lH- [l, 2,4] triazol-4-, 4- (4-acetamido-3,5-dimethylbenzyl) bromide -l-[(2R, 3R) -2- (2,4-difluorophenyl) -2-hydroxy-3-methanesulfonate Fluorenylbutyl] 2,4] triazol-4-,-bromo4- (4 · ethytoxy-3,5-dimethylbenzyl) -l-[(2R-cis) -2 -(2,4-difluorophenyl) -4- [4- [4- [4- [l-[(lS, 2S) -1-ethyl-2-hydroxypropyl) -5-oxy- 1,5-dihydro- [1,2,4] trival-4-yl] phenyl] hexahydropyrine-1-yl] phenoxymethyl] tetrahydrohanan-2-ylmethyl] -1H- [1,2,4] triazole-4-, This paper is fully used in Chinese National Standards (CNS) A4 (2I0X297 mm) ^ 11 I:---- m ^^^ 1 J. '= Ί / < ^^^ 1-' 1 --- τ ·,-«(Please read the notes on the back before filling in this page) 415947 Α8 B8 > > 蹯 8,12 · Ι6 ; :: ·· 11 Printed by the Central Government Bureau of the Ministry of Economic Affairs and the Consumers 'Cooperatives of the Ministry of Economic Affairs of the People's Republic of China.' Application for patent scope of bromide 4- (4-ethoxy-3-methylfluorenyl) _1 _ [(2-foot-cis)- 2- (2,4-difluorophenyl) -4- [4- [4- [4- [I-[(lS, 2S) -l-ethyl-2-hydroxypropyl) -5-oxy -1,5-dihydro [1,2,4] trimodal_4 · yl] phenyl] hexahydropyridine "well- 丨 _substrate oxymethyl] tetrahydrofuran_2_ylmethyl]-出-[1 , 2,4] triazole-4-, 4- (4-ethoxybenzyloxy) bromide-i-[(2R-cis) -2- (2,4-difluorophenyl) -4 -[4- [4- [4- [l-[(lS, 2S) -l-ethyl-2-superpropyl) -5-oxy-1,5 · dihydro [1,2,4] tris-4-yl] phenyl] hexahydropyridine. Well-I-yl] phenoxymethyl] tetrahydrofuran_2_ylmethyl] -exo- [1,2,4] Sanjun-4-, 4- (4-acetamidooxydigas benzyl bromide ) -I _ [(2R-cis) -2- (2,4-difluoromethylene) -4- [4- [4- [4- [I-[(lS, 2S) -l-ethyl -2-Transpropyl) -5-oxy-1,5-diaza [1,2,4] triazol-4-yl] phenyl] hexahydropyridin-1-yl] phenoxymethyl ] Tetrahydroan-2-ylmethyl] -1H- [1,2,4] triazol-4-, 4- (4-ethoxyfluoren-3-yloxy) bromide-l- [ (2R-cis) -2- (2,4-difluorophenyl) -4- [4- [4- [4- [l-[(lS, 2S) -K ethyl-2-hydroxypropyl )]-5-oxy-1,5-dihydro [1,2,4] trial-4-yl] phenyl] hexahydroeco | 1-yl] phenoxymethyl] tetrahydrooctane -2-ylmethyl] -1Η- [1,2,4] triwa-4-, 4-bromo (4-ethylacetoxy · 3,5 · dimethylmethyl) -l-[(2R , 3R) _2- (2,4-difluorophenyl) -2-hydroxy-3- [4- (4-cyanophenyl) thiazole-2 · yl] butyl] -1H- [1,2, 4] Three ton_4_, 4- (4-ethoxymethyl-3-methylfluorenyl) bromide-l-[(2R, 3R) -2- (2,4-difluorophenyl) -2- Hydroxy-3- [4- (4-cyanophenyl) thiazol-2-yl] butyl] -exo-[〖, 2,4] triazolium bromide 4- (4-ethoxybenzyloxybenzyl) Radical) -l-[(2R, 3R) -2- (2,4-di Phenyl) -2-hydroxy-3- [4- (4-cyanophenyl > selazol-2-yl] butyl] -1H- [1,2,4] triazole · 4 ·, -6 -The size of this paper is applicable to China's standard of cascade ladder (CNS) Α4 (210X297 mm) (please read the notes on the back before filling in this page) 11Τ 415947 Α8 B8 > > 蹯 8,12 · Ι6; ：: ϊΐϊΐ11, Central Government Bureau of the Ministry of Economic Affairs, Machining and Consumer Cooperatives, 11 夂 'Application for patent scope of bromide 4- (4-ethoxy-3-methylfluorenyl) _1 _ [(2 feet-cis) -2 -(2,4-difluorophenyl) -4- [4- [4- [4- [I-[(lS, 2S) -1-ethyl-2-hydroxypropyl) -5-oxy- 1,5-dihydro [1,2,4] trimodal_4-yl] phenyl] hexahydropyridine "well- 丨 _substrateoxymethyl] tetrahydrofuran_2-ylmethyl] -out- [1, 2,4] triazole-4-, 4- (4-ethoxybenzyloxy) bromide-i-[(2R-cis) -2- (2,4-difluorophenyl) -4- [4- [4- [4- [l-[(lS, 2S) -1-ethyl-2-superpropyl) -5-oxy-1,5 · dihydro [1,2,4] tri Bent-4-yl] phenyl] hexahydropyridine. Well-I-yl] phenoxymethyl] tetrahydrofuran_2_ylmethyl] -exo- [1,2,4] Sanjun-4-, 4- (4-acetamidooxydigas benzyl bromide ) -I _ [(2R-cis) -2- (2,4-difluoromethylene) -4- [4- [4- [4- [I-[(lS, 2S) -l-ethyl -2-Transpropyl) -5-oxy-1,5-diaza [1,2,4] triazol-4-yl] phenyl] hexahydropyridin-1-yl] phenoxymethyl ] Tetrahydroan-2-ylmethyl] -1H- [1,2,4] triazol-4-, 4- (4-ethoxyfluoren-3-yloxy) bromide-l- [ (2R-cis) -2- (2,4-difluorophenyl) -4- [4- [4- [4- [l-[(lS, 2S) -K ethyl-2-hydroxypropyl )]-5-oxy-1,5-dihydro [1,2,4] trial-4-yl] phenyl] hexahydroeco | 1-yl] phenoxymethyl] tetrahydrooctane -2-ylmethyl] -1Η- [1,2,4] triwa-4-, 4-bromo (4-ethylacetoxy · 3,5 · dimethylmethyl) -l-[(2R , 3R) _2- (2,4-difluorophenyl) -2-hydroxy-3- [4- (4-cyanophenyl) thiazole-2 · yl] butyl] -1H- [1,2, 4] Three ton_4_, 4- (4-ethoxymethyl-3-methylfluorenyl) bromide-l-[(2R, 3R) -2- (2,4-difluorophenyl) -2- Hydroxy-3- [4- (4-cyanophenyl) thiazol-2-yl] butyl] -exo-[〖, 2,4] triazolium bromide 4- (4-ethoxybenzyloxybenzyl) Radical) -l-[(2R, 3R) -2- (2,4-di Phenyl) -2-hydroxy-3- [4- (4-cyanophenyl > selazol-2-yl] butyl] -1H- [1,2,4] triazole · 4 ·, -6 -The size of this paper is applicable to China National Standards for Standards (CNS) Α4 (210X297 mm) (please read the notes on the back before filling in this page) 11Τ 415947 A8 B8 C8 D8 Month Ft Letter 88.12.16 Economy Consumers' Cooperatives of the Central Bureau of Standards of the People's Republic of China 6. The scope of patent applications > 4- (4-Ethyloxy-3,5-dichlorobenzyl) odor [(2R, 3R) _2_ (2 4_ Difluorophenyl) -2heptyl-3K4-cyanophenyl) B thiazol j.yl] butyl] _out [丨, 2,4] tritul-4-, / odorizing 4- (4- Ethyloxy-3-airanyl)-丨 _ [(2 | ^ 3 民) -2- (2,4-difluorophenyl) · 2_control group-3- [4- (4-cyano Phenyl) somatazole_2_yl] butyl] 丨 called 丨, 2, #] triazole_4_ Desertification 4- (4-Ethyloxy-3,5-dimethylbenzyl) small & Hydroxy_3_methyl · 3_methyl-p-aminophenylterminyl-2- (4-trifluoromethylphenyl) butyl] _1Η_ [ι, 2,4] trifluorene-4-; > 4- (4-Ethoxyphenyl-3,5-dimethylfluorenyl) small [[((5R, 6R) _2_methoxyimino-3,3-dimethyl-6-[(4 -Trifluoromethoxyphenoxy) methyl] ring []] Methyl] -exo- [1,2,4] triazole-4_, and edged 4- (4-ethynyloxy-3,5-dimethylbenzyl) _ 丨 _ [(丨 R ， 2S, 6R) _2_methoxy-3,3-dimethyl-6- (2-p-tolylethyl) cyclohexylmethyl]-丨 is called Kawagawa Triol-4- 〇 5. The compound of item No. 1 in the Red Sect of Shenqing Patent, which is selected from the group consisting of: > Smelted (2R, 3R) -4- (4-aminoethoxy-2-carboxyfluorenyl) · Bu [3_ [ 4- (4-cyano-phenyl) -〇sep-2-yl] -2- (2,4-difluorophenyl) _2-short butyl] _ιη- [1,2,4] three Azole-4 · trifluoroacetate, edged I-[(2R, 3R) -3- [4- (4-cyanophenyl) -〇thian_2_yl] · 2_ (2,4-di Fluorophenyl) -2-Ethylbutyl] -4-[(S) -3,5-dimethyl-4- (tetrahydropyrrole_2_carbonyloxy) · fluorenyl] -1H- [1 , 2,4] triazole-4-trifluoroacetate, odorized (21 ^ 311) -4- (4-aminoethoxyoxy_3,5_dimethylhanyl) small [3_ [ 4_ (4-cyanophenyl)-»Secyl-2-yl] -2- (2,4-difluorophenyl) _2_Ethylbutyl] -1Η- This paper is dimensioned to the Chinese National Standard (CNS ) A4 size (210X297mm)-(Please read the precautions on the back before filling in this page)-° 415947 A8 B8 C8 D Ft Xinzheng 88.12.16 In August, the Central Standards Bureau of the Ministry of Economic Affairs, Consumer Cooperatives, and Intentions 6. Scope of Patent Application > Stink 4- (4-Ethyloxy-3,5-dichlorobenzyl) Small [( 2R, 3R) _2_ (2 4_difluorophenyl) -2heptyl-3K4-cyanophenyl) B thiazol j · yl] butyl] _out [丨, 2,4] triturate_ 4- /, Odorized 4- (4-ethynyloxy-3-pyridyl)-丨 _ [(2 | ^ 3 民) -2- (2,4-difluorophenyl) · 2_control group- 3- [4- (4-cyanophenyl) somatazole_2_yl] butyl] 丨 called 丨, 2, #] triazole_4_ Desertification 4- (4-ethoxymethyl-3,5 -Dimethylbenzyl) small & hydroxy_3_methyl · 3_methyl-p-aminophenylterminyl-2- (4-trifluoromethylphenyl) butyl] _1Η_ [ι, 2,4] Triamidine-4-; > Deodorized 4- (4-Ethoxyphenyl-3,5-dimethylfluorenyl) small [[(5R, 6R) _2_methoxyimino-3,3- Dimethyl-6-[(4-trifluoromethoxyphenoxy) methyl] cyclohexyl] methyl] -exo- [1,2,4] triazole-4_, and marginal 4- (4 -Ethylphenoxy-3,5-dimethylbenzyl) _ 丨 _ [(丨 R, 2S, 6R) _2_methoxy-3,3-dimethyl-6- (2-p-toluene Ethyl) cyclohexylmethyl]-丨 Koukawa Sanol-4- 〇5. According to the application of Shenqing Patent Red Sister 1 Compounds, which are selected from the group consisting of: > (2R, 3R) -4- (4-aminoethylethoxy-2-carboxyfluorenyl) · [3_ [4- (4-cyano- Phenyl) -〇Sejun-2-yl] -2- (2,4-difluorophenyl) _2-short butyl] _ιη- [1,2,4] triazole-4 · trifluoroacetate , Edge I-[(2R, 3R) -3- [4- (4-cyanophenyl) -〇Sejun_2_yl] · 2_ (2,4-difluorophenyl) -2- Butyl] -4-[(S) -3,5-dimethyl-4- (tetrahydropyrrole_2_carbonyloxy) · fluorenyl] -1H- [1,2,4] triazole- 4-trifluoroacetate, odorized (21 ^ 311) -4- (4-aminoethoxyoxy_3,5_dimethylhanyl) small [3_ [4_ (4-cyanophenyl ）-»Secund-2-yl] -2- (2,4-difluorophenyl) _2_Ethylbutyl] -1Η- This paper size applies to China National Standard (CNS) A4 (210X297 mm) -(Please read the notes on the reverse side before filling in this page)-° C8i year; 'j: 乂: 1ΐδ ir. The scope of patent application for printing is printed by the Shellfish Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs [1, 2 , 4] triazole-4-trifluoroacetate, / smell (2R, 3R) -4- [4- (3-aminopropylpropoxy) _3,5_dimethylfluorenyl]! [4 [4- (4-cyanophenyl) -p-sedazole-2-yl] -2- (2,4-difluorobenzene ) _2_hydroxy, 3 · methylbutyl] -de- [1,2,4] triazole-4 · trifluoroacetate, / smell (2R, 3R) -4- [4- (4-amine -Butyryloxy) _3,5-dimethylbenzyl] ^ [4- (4-cyanophenyl) -thiazole_2-yl] -2- (2,4-difluorophenyl) _2 -Hydroxy-3_methylbutyl] -1H- [I, 2,4] triazole_4_trifluoroacetate, (211,311) -4- [4-[[2- (amine Ethylethyl] amino] ethyloxy] _35_methyl ¥ yl] -l- [3- [4- (4-cyanophenyl) sechon_2 · yl] _2_ (234-digasbenzene Group) 2-hydroxy-butyl] -1H- [1,2,4] triazole_4-trifluoroacetate, finished 1-[(2R, 3R) -3- [4- (4-cyanobenzene ) -B Saijun · 2 · yl] _2- (2,4-difluorophenyl) -2 · Cyclobutyl] -4- [4-[(S) -2,5-diaminopentyl Alkoxy] _3,5_dimethyl · pinyl] -1]-[1,2,4] triazole-4-trifluoroacetate, 4- [4-[(S) -2-amine bromide -Propionyloxy) _3,5-dimethyl and other groups] i [(2R, 3R) -3- [4- (4-cyanophenyl) -oxazodonyl] -2 · (2, 4 · Difluorophenyl peak title-butyl] -1Η- [1,2,4] triazole-4-trifluoroacetate, H (2R, 3R) -H4- (4-cyanobenzene bromide ) -Oxazol-2-yl] _2_ (2,4 · difluorophenyl) -2_short butyl H-J3,5-dimethylpyrene [( (Methylamino) ethynyloxy] methylene] _ 1Η- [1,2,4] triazole-4-trifluoroacetate, (2ί ^ 3ΙΙ) -Η3- [4- (4-cyano) Phenyl)-< Sezo_2_yl] _2- (2,4-difluorobenzyl) -2-hydroxybutyl] -4- [3,5-dimethyl-4-[(propyl Amine) ethoxy] benzyl] -1H- [1,2,4] triazole-4-trifluoroacetate, desertification 1-[(2ΐ ^ 3Κ〇-3- [4- (4- Alanyl phenyl) -pentan-2-yl] -2- (2,4-difluorophenyl) -2-hydroxybutyl] -4- [4-[(S) _2- (fluorenylamino) propyl Phenoxy] -3 allows dimethyl-Heng-8- This paper size is free to use Chinese National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before filling in {4 pages } '袈 ·. Order C8i year;' j: 乂: 1ΐδ ir. The scope of patent application [1,2,4] triazole-4-trifluoroacetate is printed by the Shellfish Consumer Cooperative of the Central Bureau of Quasi-Ministry of Economic Affairs, / Stink (2R, 3R) -4- [4- (3-Aminopropylpropoxy) _3,5_dimethylfluorenyl]! [4 [4- (4-cyanophenyl) -p plug Azole_2_yl] -2- (2,4-difluorophenyl) _2_hydroxy, 3 · methylbutyl] -de- [1,2,4] triazole-4 · trifluoroacetate, / Smelt (2R, 3R) -4- [4- (4-Amino-butyryloxy) _3,5-dimethyl section ] ^ [4- (4-cyanophenyl) -thiazole_2-yl] -2- (2,4-difluorophenyl) _2-hydroxy-3_methylbutyl] -1H- [I, 2,4] triazole-4_trifluoroacetate, (211,311) -4- [4-[[2- (aminoethylethyl) amino] ethyloxy] _35_ methyl ¥ yl] -l- [3- [4- (4-cyanophenyl) severone_2 · yl] _2_ (234-difluorophenyl) 2-hydroxy-butyl] -1H- [1,2 , 4] triazole_4_trifluoroacetate, Sinicized l-[(2R, 3R) -3- [4- (4-cyanophenyl) -B cejun · 2 · yl] _2- (2, 4-difluorophenyl) -2 · Ethylbutyl] -4- [4-[(S) -2,5-diaminopentaminyloxy] _3,5_dimethyl · pingyl]- 1Η- [1,2,4] triazole-4-trifluoroacetate, 4- [4-[(S) -2-amino-propanyloxy) _3,5-dimethyl and other groups ] i [(2R, 3R) -3- [4- (4-cyanophenyl) -oxazodonyl] -2 · (2,4 · difluorophenyl peak title-butyl] -1Η- [1,2,4] triazole-4-trifluoroacetate, H (2R, 3R) -H4- (4-cyanophenyl) -oxazol-2-yl bromide] _2_ (2,4 · Difluorophenyl) -2_short butyl H-J3,5-dimethylacetic acid [(methylamino) ethynyloxy] methylene] _ 1 _- [1,2,4] triazole-4 -Trifluoroacetate, (2ί ^ 3ΙΙ) -fluorene 3- [4- (4-cyanophenyl)-< sepazole_2_yl] _2 -(2,4-difluorobenzyl) -2-hydroxybutyl] -4- [3,5-dimethyl-4-[(propylamino) ethenyloxy] benzyl] -1H- [1,2,4] triazole-4-trifluoroacetate, desertification 1-[(2ΐ ^ 3Κ〇-3- [4- (4-aminophenyl) -pentan-2-yl]- 2- (2,4-difluorophenyl) _2_hydroxybutyl] -4- [4-[(S) _2- (fluorenylamino) propanyloxy] -3 dimethyl-Heng-8 -This paper uses Chinese National Standard (CNS) A4 size (210X297 mm) 415947 六、申請專利範圍 基]-丨H-[丨,2,4]三吐-4· 三氟醋酸鹽， f-裝-------ΪΤ (請先閲讀背面之注意事項再填馬本頁) 邊化（21^311)-卜[4-[4·(4-氣基苯基）->塞吃-2-基]_2_(2,4-二氟苯 基）-2-經基-3-甲基-丁基]-4-[3,5-二甲基-4-[3-(甲胺基）·丙醯氧 基]卞基]-1Η-[1,2,4]三峻-4- 三氟醋酸鹽， 溴化4-[4-[(S)-2-胺基-3-甲基-丁醯氧基]-3,5-二甲基爷基ρ l-[(2R，3fl)-3-[4-(4-氰基苯基）-»塞吐-2-基]-2-(2,4-二氟苯基）_2·巍 基丁基]-1H-[丨，2,4]三哇-4- 三說醋酸鹽， 溴化d3R)-l-[3-[4-(4-氰基苯基）-噻唑-2-基]-2-(2,4-二氟苯 基）-2-經基-丁基]-4-[4-[(異丙基胺基）乙酿氧基]_3,5-二甲基 芊基）-出-[1，2,4]***-4- 三氟醋酸鹽， 溴化1-[(取爪)-3-[冬(4-氰基苯基塞唑_2·基]-2-(2,4-二氟苯 基）-2-羥基丁基]-4-[(2S)-4-[2-(乙胺基）丙醯氧基]—3,5-二甲基-爷基]-11^1-[1，2,4]三吐-4- 三氟醋酸鹽， 溴化（2艮3幻-卜[3-[4-(4-氰基苯基）-嘍唑-2-基]-2-(2,4-二氟苯 基）-2-羥基丁基]-4-[4-[(乙胺基）乙醯氧基]-3,5-二甲基芊基]-1H-[1，2,4]三也-4- 三氟酿酸鹽， 經濟部中央標準局員工消费合作社印裝 溴化K2iUR)-H4-(4-氰基-苯基）-嘍唑基]-2-(2,4-二氟-苯 基）-2-羥基-丁基]-4-(3,5-二甲基-4-甲胺基乙醯氧基-竿基）-1Η-[1，2,4]***-4- 鹽酸鹽， 氣化1-(211，311)-3-[4-(4-氰基-苯基）-嘍唑-2-基]-2-(2,4-二氟-苯 基）-2-羥基-丁基]-4-(3,5-二甲基-4-甲胺基乙醯氧基-芊基）-1Η-[1，2,4]***-4- 氫溴酸鹽， 溴化1-(2民311)-3-[4-(4-氰基-笨基）-喳唑-2-基]-2-(2,4-二氟苯 基）-2-羥基-丁基]-4-(3,5-二甲基-4-甲胺基乙醢氧基-苄基 本纸張尺度適用中國國家標率（CNS) A4洗格（210X2?7公釐) ~415947 VI. Application for Patent Scope Base]-丨 H- [丨, 2,4] Triturate-4 · trifluoroacetate, f-pack -------- ΪΤ (Please read the precautions on the back before filling (From this page) Edge (21 ^ 311) -Bu [4- [4 · (4-Aminophenyl)-> Set-2-yl] _2_ (2,4-difluorophenyl) -2 -Ethyl-3-methyl-butyl] -4- [3,5-dimethyl-4- [3- (methylamino) · propanyloxy] fluorenyl] -1Η- [1,2 , 4] Sanjun-4-trifluoroacetate, 4- [4-[(S) -2-amino-3-methyl-butanyloxy] -3,5-dimethyl undecyl ρ l-[(2R, 3fl) -3- [4- (4-cyanophenyl)-»setup-2-yl] -2- (2,4-difluorophenyl) _2 Group] -1H- [丨, 2,4] triwa-4-three-acetate, d3R) -1- [3- [4- (4-cyanophenyl) -thiazol-2-yl] -2- (2,4-difluorophenyl) -2-meryl-butyl] -4- [4-[(isopropylamino) ethoxy] _3,5-dimethylfluorenyl ) -Ex- [1,2,4] triazole-4-trifluoroacetate, bromide 1-[(take claws) -3- [dong (4-cyanophenylsecazole_2 · yl]- 2- (2,4-difluorophenyl) -2-hydroxybutyl] -4-[(2S) -4- [2- (ethylamino) propanyloxy] -3,5-dimethyl -爷 基] -11 ^ 1- [1,2,4] trito-4-trifluoroacetate, brominated 3- [4- (4-cyanophenyl) -oxazol-2-yl] -2- (2,4-difluorophenyl) -2-hydroxybutyl] -4- [4-[(ethyl Amine) Ethyloxy] -3,5-dimethylfluorenyl] -1H- [1,2,4] trial-4-trifluoromalate, printed by the Consumer Cooperative of the Central Standards Bureau, Ministry of Economic Affairs K2iUR) -H4- (4-cyano-phenyl) -oxazolyl] -2- (2,4-difluoro-phenyl) -2-hydroxy-butyl] -4- (3,5 -Dimethyl-4-methylaminoethoxyl-pyridyl) -1Η- [1,2,4] triazole-4-hydrochloride, gasification of 1- (211,311) -3- [ 4- (4-cyano-phenyl) -oxazol-2-yl] -2- (2,4-difluoro-phenyl) -2-hydroxy-butyl] -4- (3,5-di Methyl-4-methylaminoethoxy-fluorenyl) -1Η- [1,2,4] triazol-4-hydrobromide, bromide 1- (2min 311) -3- [4 -(4-cyano-benzyl) -oxazol-2-yl] -2- (2,4-difluorophenyl) -2-hydroxy-butyl] -4- (3,5-dimethyl -4-Methylaminoethoxybenzyl-benzyl basic paper scale is applicable to China National Standard (CNS) A4 Washing (210X2 ~ 7mm) ~ 415947 六、申請專利範圍 基]-丨H-[丨,2,4]三吐-4· 三氟醋酸鹽， f-裝-------ΪΤ (請先閲讀背面之注意事項再填馬本頁) 邊化（21^311)-卜[4-[4·(4-氣基苯基）->塞吃-2-基]_2_(2,4-二氟苯 基）-2-經基-3-甲基-丁基]-4-[3,5-二甲基-4-[3-(甲胺基）·丙醯氧 基]卞基]-1Η-[1,2,4]三峻-4- 三氟醋酸鹽， 溴化4-[4-[(S)-2-胺基-3-甲基-丁醯氧基]-3,5-二甲基爷基ρ l-[(2R，3fl)-3-[4-(4-氰基苯基）-»塞吐-2-基]-2-(2,4-二氟苯基）_2·巍 基丁基]-1H-[丨，2,4]三哇-4- 三說醋酸鹽， 溴化d3R)-l-[3-[4-(4-氰基苯基）-噻唑-2-基]-2-(2,4-二氟苯 基）-2-經基-丁基]-4-[4-[(異丙基胺基）乙酿氧基]_3,5-二甲基 芊基）-出-[1，2,4]***-4- 三氟醋酸鹽， 溴化1-[(取爪)-3-[冬(4-氰基苯基塞唑_2·基]-2-(2,4-二氟苯 基）-2-羥基丁基]-4-[(2S)-4-[2-(乙胺基）丙醯氧基]—3,5-二甲基-爷基]-11^1-[1，2,4]三吐-4- 三氟醋酸鹽， 溴化（2艮3幻-卜[3-[4-(4-氰基苯基）-嘍唑-2-基]-2-(2,4-二氟苯 基）-2-羥基丁基]-4-[4-[(乙胺基）乙醯氧基]-3,5-二甲基芊基]-1H-[1，2,4]三也-4- 三氟酿酸鹽， 經濟部中央標準局員工消费合作社印裝 溴化K2iUR)-H4-(4-氰基-苯基）-嘍唑基]-2-(2,4-二氟-苯 基）-2-羥基-丁基]-4-(3,5-二甲基-4-甲胺基乙醯氧基-竿基）-1Η-[1，2,4]***-4- 鹽酸鹽， 氣化1-(211，311)-3-[4-(4-氰基-苯基）-嘍唑-2-基]-2-(2,4-二氟-苯 基）-2-羥基-丁基]-4-(3,5-二甲基-4-甲胺基乙醯氧基-芊基）-1Η-[1，2,4]***-4- 氫溴酸鹽， 溴化1-(2民311)-3-[4-(4-氰基-笨基）-喳唑-2-基]-2-(2,4-二氟苯 基）-2-羥基-丁基]-4-(3,5-二甲基-4-甲胺基乙醢氧基-苄基 本纸張尺度適用中國國家標率（CNS) A4洗格（210X2?7公釐) ~415947 VI. Application for Patent Scope Base]-丨 H- [丨, 2,4] Triturate-4 · trifluoroacetate, f-pack -------- ΪΤ (Please read the precautions on the back before filling (From this page) Edge (21 ^ 311) -Bu [4- [4 · (4-Aminophenyl)-> Set-2-yl] _2_ (2,4-difluorophenyl) -2 -Ethyl-3-methyl-butyl] -4- [3,5-dimethyl-4- [3- (methylamino) · propanyloxy] fluorenyl] -1Η- [1,2 , 4] Sanjun-4-trifluoroacetate, 4- [4-[(S) -2-amino-3-methyl-butanyloxy] -3,5-dimethyl undecyl ρ l-[(2R, 3fl) -3- [4- (4-cyanophenyl)-»setup-2-yl] -2- (2,4-difluorophenyl) _2 Group] -1H- [丨, 2,4] triwa-4-three-acetate, d3R) -1- [3- [4- (4-cyanophenyl) -thiazol-2-yl] -2- (2,4-difluorophenyl) -2-meryl-butyl] -4- [4-[(isopropylamino) ethoxy] _3,5-dimethylfluorenyl ) -Ex- [1,2,4] triazole-4-trifluoroacetate, bromide 1-[(take claws) -3- [dong (4-cyanophenylsecazole_2 · yl]- 2- (2,4-difluorophenyl) -2-hydroxybutyl] -4-[(2S) -4- [2- (ethylamino) propanyloxy] -3,5-dimethyl -爷 基] -11 ^ 1- [1,2,4] trito-4-trifluoroacetate, brominated 3- [4- (4-cyanophenyl) -oxazol-2-yl] -2- (2,4-difluorophenyl) -2-hydroxybutyl] -4- [4-[(ethyl Amine) Ethyloxy] -3,5-dimethylfluorenyl] -1H- [1,2,4] trial-4-trifluoromalate, printed by the Consumer Cooperative of the Central Standards Bureau, Ministry of Economic Affairs K2iUR) -H4- (4-cyano-phenyl) -oxazolyl] -2- (2,4-difluoro-phenyl) -2-hydroxy-butyl] -4- (3,5 -Dimethyl-4-methylaminoethoxyl-pyridyl) -1Η- [1,2,4] triazole-4-hydrochloride, gasification of 1- (211,311) -3- [ 4- (4-cyano-phenyl) -oxazol-2-yl] -2- (2,4-difluoro-phenyl) -2-hydroxy-butyl] -4- (3,5-di Methyl-4-methylaminoethoxy-fluorenyl) -1Η- [1,2,4] triazol-4-hydrobromide, bromide 1- (2min 311) -3- [4 -(4-cyano-benzyl) -oxazol-2-yl] -2- (2,4-difluorophenyl) -2-hydroxy-butyl] -4- (3,5-dimethyl -4-Methylaminoethoxybenzyl-benzyl basic paper scale is applicable to China National Standard (CNS) A4 Washing (210X2 ~ 7mm) ~ X 化合物 415947 '申請專利範圍 [1，2,4]***_4- 鹽酸鹽。 6 種製造通式®化合物以及其鹽、水合物、溶劑合物之 方法 ⑴ 其中R1至圮、Q、X-及Z均具有如申請專利範圍第！ 項之相同意義，其包括使具有抗真菌活悻之通式⑼唑 ---------ύ (請先聞讀背面之注$項再4寫\頁} C 一 〇 (II) 訂 R2X compound 415947 'Applicable patent scope [1,2,4] triazole-4-hydrochloride. 6 ways to make compounds of general formula ® and their salts, hydrates, and solvates The term has the same meaning, which includes the general formula oxazole with antifungal activity --------- ύ (please read the note $ item on the back before writing 4 pages \) Order R2 經濟部申夬揉準局員工消费合作社印装 與通式（III)化合物反應 (III) 其中R1至R4均與申請專利範圍第1項相同，且其中存 在於Ri或R2中之胺基’可呈經保護形式；及L為脫離 基， 接著’若必要則移除保護基及/或進行鹽形成。 7.根據申請專利範圍第6項之方法’其係用以製造根據申 -10 - 本紙張尺度逋用中國國家揉率（CNS ) Α4洗格（210X297公釐）Ministry of Economic Affairs, the Bureau of Staff of the Bureau of Economic Affairs, printed the reaction of the consumer cooperatives with compounds of the general formula (III) (III) where R1 to R4 are the same as the scope of the patent application, and the amine group in Ri or R2 can be In a protected form; and L is a leaving group, followed by 'removing the protecting group if necessary and / or performing salt formation. 7. Method according to item 6 of the scope of patent application ', which is used to manufacture according to the application -10-This paper size uses China National Kneading Rate (CNS) Α4 wash grid (210X297 mm) X 化合物 415947 '申請專利範圍 [1，2,4]***_4- 鹽酸鹽。 6 種製造通式®化合物以及其鹽、水合物、溶劑合物之 方法 ⑴ 其中R1至圮、Q、X-及Z均具有如申請專利範圍第！ 項之相同意義，其包括使具有抗真菌活悻之通式⑼唑 ---------ύ (請先聞讀背面之注$項再4寫\頁} C 一 〇 (II) 訂 R2X compound 415947 'Applicable patent scope [1,2,4] triazole-4-hydrochloride. 6 ways to make compounds of general formula ® and their salts, hydrates, and solvates The term has the same meaning, which includes the general formula oxazole with antifungal activity --------- ύ (please read the note $ item on the back before writing 4 pages \) Order R2 經濟部申夬揉準局員工消费合作社印装 與通式（III)化合物反應 (III) 其中R1至R4均與申請專利範圍第1項相同，且其中存 在於Ri或R2中之胺基’可呈經保護形式；及L為脫離 基， 接著’若必要則移除保護基及/或進行鹽形成。 7.根據申請專利範圍第6項之方法’其係用以製造根據申 -10 - 本紙張尺度逋用中國國家揉率（CNS ) Α4洗格（210X297公釐） 455947 A8 BS C8 D8 年月Η ΤΓ-、卜i 、申請專利範圍 ••一上丨 請專利範圍第2項之化合物，其包括使根據申請專利範 圍第6項之通式（II)化合物與根據申請專利範圍第6項之 通式（ΙΠ)化合物反應，其中R1或R2之一為羥基，接著是 所形成化合物與式R5COL之反應，其中R5CO為經N-保 護之胺基酸之醯基殘基，或R5為氫、Cw烷氧基、Cw烷 基’其可视情況被幾基、胺基、具有或未具有保護基之 Q_5烷胺基、吡啶基或苯基取代，且l為脫離基。 8. —種抗真菌組合物，其包含根據申請專利範圍第1至4 項中任一項之化合物，.及載劑》 9. 根據申請專利範圍第1至4項中任一項之化合物，其係 使用於製造治療真菌感染用之藥劑= 10. 根據申請專利範圍第1項之化合物，其具有式I’ P^-COO-^V^M+^i. X，· (1-) . ' V^N-Q 其中： R 為直鍵或分枝狀Ci -C5燒!基 '苯基、峨咬 經濟部中央標车局具工消费合作社印繁 (请先閲讀背面之注意事項再填寫本頁) 基、四氫吡咯基或A-NH-B-基團（其中a 為氫原子或直鏈或分枝狀q -C5燒基；B 為直鏈或分枝狀次貌基、-CH2- conh-ch2 -或-ch2 ch2 ch2 -CH(NH2)-); R3與R4 各獨立為氫或鹵原子或C】_5燒氧基；及 Z、Q及X-均如申請專利範圍第1項中之定義。 _ -11 - 本紙張Aviit财CNS ) A4^ ( 21GX297公釐) 455947 A8 BS C8 D8 年月Η ΤΓ-、卜i 、申請專利範圍 ••一上丨 請專利範圍第2項之化合物，其包括使根據申請專利範 圍第6項之通式（II)化合物與根據申請專利範圍第6項之 通式（ΙΠ)化合物反應，其中R1或R2之一為羥基，接著是 所形成化合物與式R5COL之反應，其中R5CO為經N-保 護之胺基酸之醯基殘基，或R5為氫、Cw烷氧基、Cw烷 基’其可视情況被幾基、胺基、具有或未具有保護基之 Q_5烷胺基、吡啶基或苯基取代，且l為脫離基。 8. —種抗真菌組合物，其包含根據申請專利範圍第1至4 項中任一項之化合物，.及載劑》 9. 根據申請專利範圍第1至4項中任一項之化合物，其係 使用於製造治療真菌感染用之藥劑= 10. 根據申請專利範圍第1項之化合物，其具有式I’ P^-COO-^V^M+^i. X，· (1-) . ' V^N-Q 其中： R 為直鍵或分枝狀Ci -C5燒!基 '苯基、峨咬 經濟部中央標车局具工消费合作社印繁 (请先閲讀背面之注意事項再填寫本頁) 基、四氫吡咯基或A-NH-B-基團（其中a 為氫原子或直鏈或分枝狀q -C5燒基；B 為直鏈或分枝狀次貌基、-CH2- conh-ch2 -或-ch2 ch2 ch2 -CH(NH2)-); R3與R4 各獨立為氫或鹵原子或C】_5燒氧基；及 Z、Q及X-均如申請專利範圍第1項中之定義。 _ -11 - 本紙張Aviit财CNS ) A4^ ( 21GX297公釐)Ministry of Economic Affairs, the Bureau of Staff of the Bureau of Economic Affairs, printed the reaction of the consumer cooperatives with compounds of the general formula (III) (III) where R1 to R4 are the same as the scope of the patent application, and the amine group in Ri or R2 can be In a protected form; and L is a leaving group, followed by 'removing the protecting group if necessary and / or performing salt formation. 7. Method according to item 6 of the scope of patent application 'It is used to manufacture according to Shen-10-This paper size uses Chinese National Kneading Rate (CNS) Α4 Washing (210X297 mm) 455947 A8 BS C8 D8 Month Η ΤΓ-, i, patent application scope •• One above 丨 Company No. 2 in the scope of patent application, which includes a general formula (II) compound in accordance with the scope of patent application No. 6 Reaction of a compound of formula (II), wherein one of R1 or R2 is a hydroxyl group, followed by a reaction of the formed compound with formula R5COL, wherein R5CO is a fluorenyl residue of an N-protected amino acid, or R5 is hydrogen, Cw An alkoxy group or a Cw alkyl group may be optionally substituted with a aryl group, an amine group, a Q_5 alkylamino group with or without a protective group, a pyridyl group, or a phenyl group, and l is an leaving group. 8. An antifungal composition comprising a compound according to any one of claims 1 to 4, and a carrier "9. A compound according to any one of claims 1 to 4, It is used in the manufacture of a medicament for the treatment of fungal infections = 10. The compound according to item 1 of the scope of patent application, which has the formula I 'P ^ -COO- ^ V ^ M + ^ i. X, · (1-).' V ^ NQ Among them: R is a straight bond or branched Ci-C5 burnt! Base 'phenyl, E bite, Ministry of Economic Affairs, Central Standard Vehicle Bureau, Gugong Consumer Cooperative, India (please read the precautions on the back before filling this page) Group, tetrahydropyrrolyl group or A-NH-B- group (where a is a hydrogen atom or a linear or branched q-C5 alkyl group; B is a linear or branched subordinate group, -CH2- conh -ch2-or -ch2 ch2 ch2 -CH (NH2)-); R3 and R4 are each independently a hydrogen or halogen atom or C] _5 alkoxy; and Z, Q, and X- are as described in item 1 of the scope of patent application Definition. _ -11-Aviit Choi CNS of this paper) A4 ^ (21GX297 mm) 455947 A8 BS C8 D8 Month Τ Γ-, BU i, patent application scope Reacting a compound of general formula (II) according to item 6 of the patent application with a compound of general formula (II) according to item 6 of the patent application, wherein one of R1 or R2 is a hydroxyl group, followed by the formed compound and the compound of formula R5COL Reaction, in which R5CO is a fluorenyl residue of an N-protected amino acid, or R5 is hydrogen, Cw alkoxy, Cw alkyl ', which may optionally be protected by several groups, amine groups, with or without protective groups Q-5 alkylamino, pyridyl or phenyl substituted, and l is a leaving group. 8. An antifungal composition comprising a compound according to any one of claims 1 to 4, and a carrier "9. A compound according to any one of claims 1 to 4, It is used in the manufacture of a medicament for the treatment of fungal infections = 10. The compound according to item 1 of the scope of patent application, which has the formula I 'P ^ -COO- ^ V ^ M + ^ i. X, · (1-).' V ^ NQ Among them: R is a straight bond or branched Ci-C5 burnt! Base 'phenyl, E bite, Ministry of Economic Affairs, Central Standard Vehicle Bureau, Gugong Consumer Cooperative, India (please read the precautions on the back before filling this page) Group, tetrahydropyrrolyl group or A-NH-B- group (where a is a hydrogen atom or a linear or branched q-C5 alkyl group; B is a linear or branched subordinate group, -CH2- conh -ch2-or -ch2 ch2 ch2 -CH (NH2)-); R3 and R4 are each independently a hydrogen or halogen atom or C] _5 alkoxy; and Z, Q, and X- are as described in item 1 of the scope of patent application Definition. _ -11-Aviit Choi CNS of this paper) A4 ^ (21GX297 mm) 々、申請專利範圍 11.根據申請專利範圍第1或2項之經取代唑化合物，其中Q 為下式基團 B C范围 、 Scope of patent application 11. The substituted azole compound according to item 1 or 2 of the scope of patent application, wherein Q is a group of the formula B C CM (Q 或 、ch2CM (Q or, ch2 丁 (請先聞讀背面之注意事項再填寫本頁) 訂 其中 D為Cw烷醯基或下式基團Ding (please read the precautions on the back before filling this page) Order D is Cw alkyl group or the following formula 經濟部中央棣隼局員工消費合作社印装 R7為鹵原子；及 · R8為直鏈或分枝狀^-仏烷基 -12 本紙》尺度適用中國國家#準（CNS ) A4規格（210X297公釐）The R7 is a halogen atom printed on the Consumer Cooperatives of the Central Government Bureau of the Ministry of Economic Affairs; ) 々、申請專利範圍 11.根據申請專利範圍第1或2項之經取代唑化合物，其中Q 為下式基團 B C范围 、 Scope of patent application 11. The substituted azole compound according to item 1 or 2 of the scope of patent application, wherein Q is a group of the formula B C CM (Q 或 、ch2CM (Q or, ch2 丁 (請先聞讀背面之注意事項再填寫本頁) 訂 其中 D為Cw烷醯基或下式基團Ding (please read the precautions on the back before filling this page) Order D is Cw alkyl group or the following formula 經濟部中央棣隼局員工消費合作社印装 R7為鹵原子；及 · R8為直鏈或分枝狀^-仏烷基 -12 本紙》尺度適用中國國家#準（CNS ) A4規格（210X297公釐）The R7 is a halogen atom printed on the Consumer Cooperatives of the Central Government Bureau of the Ministry of Economic Affairs; )