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【结 构 式】 
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【分子编号】30071 【品名】(3S,8R,9S,10R,13S,14S,16R)-16-fluoro-3-hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one 【CA登记号】 |
【 分 子 式 】C19H27FO2 【 分 子 量 】306.4205832 【元素组成】C 74.48% H 8.88% F 6.2% O 10.44% |
合成路线1
该中间体在本合成路线中的序号：(IV)Beckmann rearrangement of oxime (I) in the presence of p-acetamidobenzenesulfonyl chloride and pyridine afforded acetamide (II). Subsequent fluorination of (II) using perchloryl fluoride produced fluoroenamide (III), which was hydrolyzed with HCl to give fluoroketone (IV). After treatmentof (IV) with o-phenylenephosphorochloridite (V) and pyridine, the intermediate phosphite ester (VI) was converted to iodide (VII) by means of iodine in CH2Cl2. Finally, reductive deiodination of (VI) with Zn in AcOH produced the target compound.
| 【1】 Lewbart, M.L.; Schwartz, A.G. (Research Corporation Technologies, Inc.); Steroids useful as anti-cancer and anti-obesity agents, a therapeutic compsn. containing them and use thereof for the preparation of a therapeutic compsn.. EP 0246650; JP 1987283993 . |
| 【2】 Schwartz, A.G.; Lewbart, M.L.; 17-Hydroxy-steroids. US 4898694 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 19362 | 4-(acetamido)benzenesulfonyl chloride; N-acetylsulfanilyl chloride | 121-60-8 | C8H8ClNO3S | 详情 | 详情 |
| (I) | 30068 | (3S,8R,9S,10R,13S,14S)-17-ethanimidoyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C23H33NO3 | 详情 | 详情 | |
| (II) | 30069 | (3S,8R,9S,10R,13S,14S)-17-(acetamido)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C23H33NO3 | 详情 | 详情 | |
| (III) | 30070 | (3S,8R,9S,10R,13S,14S)-17-(acetamido)-16-fluoro-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C23H32FNO3 | 详情 | 详情 | |
| (IV) | 30071 | (3S,8R,9S,10R,13S,14S,16R)-16-fluoro-3-hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one | C19H27FO2 | 详情 | 详情 | |
| (V) | 30072 | 2-chloro-1,3,2-benzodioxaphosphole | 1641-40-3 | C6H4ClO2P | 详情 | 详情 |
| (VI) | 30073 | (3S,8R,9S,10R,13S,14S,16R)-3-(1,3,2-benzodioxaphosphol-2-yloxy)-16-fluoro-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one | C25H30FO4P | 详情 | 详情 | |
| (VII) | 30074 | (3S,8R,9S,10R,13S,14S,16R)-16-fluoro-3-iodo-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one | C19H26FIO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)Dehydroepiandrosterone (VIII) was first brominated with CuBr2 to give bromoketone (XIV), which was hydrolyzed to hydroxyketone (XV). After protection of (XV) as the monoacetate (XVI), fluorination at position 16 by means of (2-chloro-1,1,2-trifluoroethyl)amine (XIII) afforded fluoroketone (XVII). Ester hydrolysis in (XVI) then gave intermediate (IV).
| 【1】 Schwartz, A.G.; Lewbart, M.L.; 17-Hydroxy-steroids. US 4898694 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 30071 | (3S,8R,9S,10R,13S,14S,16R)-16-fluoro-3-hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one | C19H27FO2 | 详情 | 详情 | |
| (VIII) | 11713 | Dehydroepiandrosterone;prasterone；(3S,8R,9S,10R,13S,14S)-3-Hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one | 53-43-0 | C19H28O2 | 详情 | 详情 |
| (XIII) | 30079 | 2-chloro-N,N-diethyl-1,1,2-trifluoro-1-ethanamine; N-(2-chloro-1,1,2-trifluoroethyl)-N,N-diethylamine | C6H11ClF3N | 详情 | 详情 | |
| (XIV) | 30080 | (3S,8R,9S,10R,13S,14S,16R)-16-bromo-3-hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one | C19H27BrO2 | 详情 | 详情 | |
| (XV) | 30081 | (3S,8R,9S,10R,13S,14S,16R)-3,16-dihydroxy-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one | C19H28O3 | 详情 | 详情 | |
| (XVI) | 30082 | (3S,8R,9S,10R,13S,14S,16R)-16-hydroxy-10,13-dimethyl-17-oxo-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C21H30O4 | 详情 | 详情 | |
| (XVII) | 30083 | (3S,8R,9S,10R,13S,14S,16R)-16-fluoro-10,13-dimethyl-17-oxo-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C21H29FO3 | 详情 | 详情 |