CN105017363A - 3-酮-4-雄烯-17β羧酸及其甲酯的合成方法 - Google Patents
3-酮-4-雄烯-17β羧酸及其甲酯的合成方法 Download PDFInfo
- Publication number
- CN105017363A CN105017363A CN201510358116.7A CN201510358116A CN105017363A CN 105017363 A CN105017363 A CN 105017363A CN 201510358116 A CN201510358116 A CN 201510358116A CN 105017363 A CN105017363 A CN 105017363A
- Authority
- CN
- China
- Prior art keywords
- compound
- synthetic method
- generation
- solvent
- ketone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- YQACAXHKQZCEOI-UDCWSGSHSA-N (8s,9s,10r,13s,14s,17s)-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthrene-17-carboxylic acid Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(O)=O)[C@@H]4[C@@H]3CCC2=C1 YQACAXHKQZCEOI-UDCWSGSHSA-N 0.000 title abstract 3
- XWFWMYFLNHTEBF-YFWFAHHUSA-N methyl (8s,9s,10r,13s,14s,17s)-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthrene-17-carboxylate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)OC)[C@@]1(C)CC2 XWFWMYFLNHTEBF-YFWFAHHUSA-N 0.000 title abstract 3
- 238000001308 synthesis method Methods 0.000 title abstract 3
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 claims abstract description 21
- 229960003604 testosterone Drugs 0.000 claims abstract description 10
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 7
- 238000006266 etherification reaction Methods 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 71
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 52
- 238000006243 chemical reaction Methods 0.000 claims description 34
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 25
- 238000010189 synthetic method Methods 0.000 claims description 24
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 22
- 239000002904 solvent Substances 0.000 claims description 19
- 239000007818 Grignard reagent Substances 0.000 claims description 14
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 14
- -1 carboxylate methyl ester Chemical class 0.000 claims description 14
- 150000004795 grignard reagents Chemical class 0.000 claims description 14
- 239000011777 magnesium Substances 0.000 claims description 14
- 229910052749 magnesium Inorganic materials 0.000 claims description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 11
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 claims description 10
- CXHHBNMLPJOKQD-UHFFFAOYSA-M methyl carbonate Chemical compound COC([O-])=O CXHHBNMLPJOKQD-UHFFFAOYSA-M 0.000 claims description 9
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 8
- 235000011089 carbon dioxide Nutrition 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000003377 acid catalyst Substances 0.000 claims description 4
- 238000007259 addition reaction Methods 0.000 claims description 4
- 238000006713 insertion reaction Methods 0.000 claims description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 8
- 230000007613 environmental effect Effects 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 3
- QZLYKIGBANMMBK-UGCZWRCOSA-N 5α-Androstane Chemical compound C([C@@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CCC[C@@]2(C)CC1 QZLYKIGBANMMBK-UGCZWRCOSA-N 0.000 abstract 1
- 239000007795 chemical reaction product Substances 0.000 abstract 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 229960000583 acetic acid Drugs 0.000 description 5
- 235000019270 ammonium chloride Nutrition 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 150000004702 methyl esters Chemical class 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 5
- 229930182490 saponin Natural products 0.000 description 5
- 150000007949 saponins Chemical class 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 238000009413 insulation Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- LBJNMUFDOHXDFG-UHFFFAOYSA-N copper;hydrate Chemical compound O.[Cu].[Cu] LBJNMUFDOHXDFG-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- 238000003747 Grignard reaction Methods 0.000 description 2
- 235000010675 chips/crisps Nutrition 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000010025 steaming Methods 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- 235000020679 tap water Nutrition 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- 201000004384 Alopecia Diseases 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 235000003392 Curcuma domestica Nutrition 0.000 description 1
- 244000008991 Curcuma longa Species 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 235000003373 curcuma longa Nutrition 0.000 description 1
- 229960004199 dutasteride Drugs 0.000 description 1
- JWJOTENAMICLJG-QWBYCMEYSA-N dutasteride Chemical compound O=C([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)N[C@@H]4CC3)C)CC[C@@]21C)NC1=CC(C(F)(F)F)=CC=C1C(F)(F)F JWJOTENAMICLJG-QWBYCMEYSA-N 0.000 description 1
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
- 229960004039 finasteride Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 235000013976 turmeric Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J3/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by one carbon atom
- C07J3/005—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by one carbon atom the carbon atom being part of a carboxylic function
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Abstract
Description
Claims (10)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510358116.7A CN105017363B (zh) | 2015-06-25 | 2015-06-25 | 3-酮-4-雄烯-17β羧酸及其甲酯的合成方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510358116.7A CN105017363B (zh) | 2015-06-25 | 2015-06-25 | 3-酮-4-雄烯-17β羧酸及其甲酯的合成方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105017363A true CN105017363A (zh) | 2015-11-04 |
CN105017363B CN105017363B (zh) | 2016-12-07 |
Family
ID=54407709
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201510358116.7A Active CN105017363B (zh) | 2015-06-25 | 2015-06-25 | 3-酮-4-雄烯-17β羧酸及其甲酯的合成方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105017363B (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109467584A (zh) * | 2018-11-23 | 2019-03-15 | 湖南玉新药业有限公司 | 雄甾-4-烯-3-酮-17β-羧酸甲酯的合成方法 |
EP3875464A1 (en) * | 2020-03-06 | 2021-09-08 | F.I.S.- Fabbrica Italiana Sintetici S.p.A. | Process for the purification of etiocholenic acid |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1182091A (zh) * | 1996-11-29 | 1998-05-20 | 中国科学院上海有机化学研究所 | 一种含氟甾体5α-还原酶抑制剂、合成方法及其用途 |
CN1306005A (zh) * | 2001-01-18 | 2001-08-01 | 湖南正清制药集团股份有限公司 | 一种药物的生产方法 |
CN104262442A (zh) * | 2014-10-10 | 2015-01-07 | 湖南科瑞生物科技有限公司 | ***的制备方法 |
CN104327146A (zh) * | 2014-10-24 | 2015-02-04 | 湖南科瑞生物科技有限公司 | 一种合成17α-羟基***的新方法 |
-
2015
- 2015-06-25 CN CN201510358116.7A patent/CN105017363B/zh active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1182091A (zh) * | 1996-11-29 | 1998-05-20 | 中国科学院上海有机化学研究所 | 一种含氟甾体5α-还原酶抑制剂、合成方法及其用途 |
CN1306005A (zh) * | 2001-01-18 | 2001-08-01 | 湖南正清制药集团股份有限公司 | 一种药物的生产方法 |
CN104262442A (zh) * | 2014-10-10 | 2015-01-07 | 湖南科瑞生物科技有限公司 | ***的制备方法 |
CN104327146A (zh) * | 2014-10-24 | 2015-02-04 | 湖南科瑞生物科技有限公司 | 一种合成17α-羟基***的新方法 |
Non-Patent Citations (1)
Title |
---|
GAMAL A. ELMEGEED ET AL.: "Cytotoxicity and gene expression profiles of novel synthesized steroid derivatives as chemotherapeutic anti-breast cancer agents", 《BIOORGANIC & MEDICINAL CHEMISTRY》 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109467584A (zh) * | 2018-11-23 | 2019-03-15 | 湖南玉新药业有限公司 | 雄甾-4-烯-3-酮-17β-羧酸甲酯的合成方法 |
CN109467584B (zh) * | 2018-11-23 | 2021-05-11 | 湖南玉新药业有限公司 | 雄甾-4-烯-3-酮-17β-羧酸甲酯的合成方法 |
EP3875464A1 (en) * | 2020-03-06 | 2021-09-08 | F.I.S.- Fabbrica Italiana Sintetici S.p.A. | Process for the purification of etiocholenic acid |
CN113429449A (zh) * | 2020-03-06 | 2021-09-24 | F.I.S.-菲博利佳意大利合成面料股份公司 | 纯化本胆烯酸的方法 |
Also Published As
Publication number | Publication date |
---|---|
CN105017363B (zh) | 2016-12-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN104876995A (zh) | 鹅去氧胆酸衍生物的制备方法 | |
CN105348045A (zh) | 一种利用连续流反应合成五氟苯酚的方法 | |
CN102030652A (zh) | 复合催化合成偏苯三酸三辛酯的工业化生产方法 | |
CN105017363A (zh) | 3-酮-4-雄烯-17β羧酸及其甲酯的合成方法 | |
CN104311625B (zh) | 一种醋酸氟轻松中间体的制备方法 | |
CN103275308B (zh) | 含磷阻燃水性醇酸树脂及其制备方法 | |
CN102633836B (zh) | 一种合成双(二苯基膦)烷烃的方法 | |
CN104945458A (zh) | 一种***的合成方法 | |
CN102942444B (zh) | 一种2,2’-二溴-9,9’-螺二芴的合成方法 | |
CN105859761B (zh) | 一种芳香硼酸酯化合物合成方法 | |
CN103421023B (zh) | 一种替西罗莫司的合成工艺 | |
CN106518944A (zh) | 甲基***的制备方法 | |
CN104558091B (zh) | 一种醋酸阿比特龙的合成方法 | |
CN104860821A (zh) | 一种二元酸单酸单酯及其制备方法 | |
CN105399790A (zh) | 一种3-酮-4-雄烯-17β羧酸的合成方法 | |
CN104513222B (zh) | 一种药物中间体的合成方法 | |
CN101823943A (zh) | 反-4-(反-4′-烷基环己基)环己基甲醛的制备方法 | |
CN104592283A (zh) | 硅烷偶联剂Si-69的合成工艺 | |
CN106916089B (zh) | 一种选择性合成顺式4-正戊基环己硫醇的制备方法 | |
CN102503795A (zh) | 紫外线吸收剂uv-531的合成工艺 | |
CN101747357A (zh) | 一种制备辛伐他汀中间体-辛伐酰胺二硅醚的方法 | |
CN110294782B (zh) | 一种11烯甾体化合物的制备方法 | |
CN105732757A (zh) | ***的制备方法 | |
CN116574084A (zh) | 一种噻吩衍生物及其合成方法与应用 | |
CN101475508A (zh) | 2,6-二乙基-n-(2-丙氧乙基)乙酰苯胺的生产工艺 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
CB02 | Change of applicant information |
Address after: 422900 Xinshao Economic Development Zone, Shaoyang Province, Xing Road, economic development zone, Hunan Applicant after: HUNAN KEREY PHARMACEUTICAL Co.,Ltd. Address before: 422900 Xinshao Economic Development Zone, Shaoyang Province, Xing Road, economic development zone, Hunan Applicant before: HUNAN KERY BIOTECHNOLOGY CO.,LTD. |
|
COR | Change of bibliographic data | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Synthesis of 3-keto-4-androsten-17 b carboxylic acid and its methyl ester Effective date of registration: 20200928 Granted publication date: 20161207 Pledgee: China Co. truction Bank Corp Xinshao branch Pledgor: HUNAN KEREY PHARMACEUTICAL Co.,Ltd. Registration number: Y2020980006554 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20230131 Granted publication date: 20161207 Pledgee: China Co. truction Bank Corp Xinshao branch Pledgor: HUNAN KEREY PHARMACEUTICAL Co.,Ltd. Registration number: Y2020980006554 |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: 3-keto-4-androsten-17 b Synthesis methods of carboxylic acids and their methyl esters Granted publication date: 20161207 Pledgee: Industrial and Commercial Bank of China Limited Shaoyang Beita Branch Pledgor: HUNAN KEREY PHARMACEUTICAL Co.,Ltd. Registration number: Y2024980006163 |