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【结 构 式】 
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【分子编号】59455 【品名】(4aS,4bR,5S,6aS,8R,9aR,10aS,10bS,12S)-5-(acetyloxy)-4b,12-difluoro-4a,6a-dimethyl-2-oxo-8-propyl-2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxole-6b-carboxylic acid 【CA登记号】 |
【 分 子 式 】C26H32F2O7 【 分 子 量 】494.5326864 【元素组成】C 63.15% H 6.52% F 7.68% O 22.65% |
合成路线1
该中间体在本合成路线中的序号：(XII)In a related method, the dihydroxy steroid (IX) was converted to the 11-acetate ester (XI) via diacetylation with Ac2O and DMAP, followed by selective hydrolysis of the resultant 11,21-diacetate (X) under acidic conditions. Oxidative cleavage of the hydroxy ketone moiety of (XI) using periodic acid furnished the carboxylic acid (XII). The 1,2-double bond of (XII) was selectively reduced by hydrogenation in the presence of tris(triphenylphosphine)rhodium chloride to yield (XIII). Activation of (XIII) as the corresponding mixed anhydride with diethyl chlorophosphate, followed by coupling with N-hydroxy-2-thiopyridone (XIV), furnished the pyridyl ester (XV). Radical decarboxylation of (XV) in the presence of dimethyl disulfide gave rise to the methyl thioether (XVI). The acetate ester of (XVI) was finally hydrolyzed using LiOH in aqueous EtOH or, alternatively, K2CO3, NaOH or KOH in MeOH/H2O.
| 【1】 Bridge, A.W.; Mcfarlane, I.M.; Parkinson, N.C. (Aventis Pharma SA); Process for the preparation of (20R)-16alpha, 17alpha-butylidenedioxy-6alpha, 9alpha-difluoro-11beta-hydroxy-17beta-(methylthio)androst-4-en-3-one. WO 9631524 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 47570 | (4aS,4bR,5S,6aS,6bS,8R,9aR,10aS,10bS,12S)-4b,12-difluoro-6b-glycoloyl-5-hydroxy-4a,6a-dimethyl-8-propyl-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-2-one | C25H32F2O6 | 详情 | 详情 | |
| (X) | 59453 | 2-[(4aS,4bR,5S,6aS,8R,9aR,10aS,10bS,12S)-5-(acetyloxy)-4b,12-difluoro-4a,6a-dimethyl-2-oxo-8-propyl-2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-6-yl]-2-oxoethyl acetate | C29H36F2O8 | 详情 | 详情 | |
| (XI) | 59454 | (4aS,4bR,5S,6aS,6bS,8R,9aR,10aS,10bS,12S)-4b,12-difluoro-6b-glycoloyl-4a,6a-dimethyl-2-oxo-8-propyl-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-5-yl acetate | C27H34F2O7 | 详情 | 详情 | |
| (XII) | 59455 | (4aS,4bR,5S,6aS,8R,9aR,10aS,10bS,12S)-5-(acetyloxy)-4b,12-difluoro-4a,6a-dimethyl-2-oxo-8-propyl-2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxole-6b-carboxylic acid | C26H32F2O7 | 详情 | 详情 | |
| (XIII) | 59456 | (4aS,4bR,5S,6aS,8R,9aR,10aS,10bS,12S)-5-(acetyloxy)-4b,12-difluoro-4a,6a-dimethyl-2-oxo-8-propyl-2,3,4,4a,4b,5,6,6a,9a,10,10a,10b,11,12-tetradecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxole-6b-carboxylic acid | C26H34F2O7 | 详情 | 详情 | |
| (XIV) | 59457 | 1-hydroxy-2(1H)-pyridinethione | C5H5NOS | 详情 | 详情 | |
| (XV) | 59458 | (4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS,12S)-4b,12-difluoro-4a,6a-dimethyl-2-oxo-8-propyl-6b-({[2-thioxo-1(2H)-pyridinyl]oxy}carbonyl)-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-5-yl acetate | C31H35F2NO7S | 详情 | 详情 | |
| (XVI) | 59459 | (4aS,4bR,5S,6aS,6bR,8R,9aR,10aS,10bS,12S)-4b,12-difluoro-4a,6a-dimethyl-6b-(methylsulfanyl)-2-oxo-8-propyl-3,4,4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-tetradecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-5-yl acetate | C26H36F2O5S | 详情 | 详情 |