|
【结 构 式】 
|
【分子编号】22447 【品名】(8S,9S,10R,13S,14S,17S)-N-[2,5-bis(trifluoromethyl)phenyl]-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-carboxamide 【CA登记号】 |
【 分 子 式 】C28H31F6NO2 【 分 子 量 】527.5500992 【元素组成】C 63.75% H 5.92% F 21.61% N 2.66% O 6.07% |
合成路线1
该中间体在本合成路线中的序号：(IV)1) The reaction of 3-oxo-4-androstene-17beta-carboxylic acid (I) with SOCl2/pyridine in THF gives the acyl chloride (II), which is condensed with 2,5-bis(trifluoromethyl)aniline (III) by means of pyridine in refluxing THF, yielding amide (IV). The oxidation of (IV) with KMnO4/NaIO4/Na2CO3 in refluxing tert-butanol/water affords the seco-steroid (V), which is cyclized with NH3 in ethylene glycol at 180 C to give the 5-unsaturated azasteroid (VI). The hydrogenation of (VI) with H2 over PtO2 in acetic acid yields the saturated azasteroid (VII), which is finally dehydrogenated by means of 2,3-dichloro-5,6-dicyanobenzoquinone (DCQ)/bis(trimethylsilyl)trifluoroacetamide in dioxane.
| 【1】 Ellsworth, K.; Mosley, R.T.; Chang, B.; Rasmusson, G.H.; Harris, G.S.; Patel, G.F.; Tolman, R.L.; Bakshi, R.K.; 4-Aza-3-oxo-5alpha-androst-1-ene-17beta-N-aryl-car. J Med Chem 1995, 38, 17, 3189. |
| 【2】 Graul, A.; Silvestre, J.S.; Castañer, J.; Dutasteride. Drugs Fut 1999, 24, 3, 246. |
| 【3】 Rasmusson, G.H.; Reynolds, G.F.; Steinberg, N.G.; Walton, E.; Patel, G.F.; Liang, T.; Cascieri, M.A.; Cheung, A.H.; Brooks, J.R.; Berman, C.; Azasteroids: structure-activity relationships for inhibition of 5 alpha-reductase and of androgen receptor binding. J Med Chem 1986, 29, 11, 2298. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 14892 | (8S,9S,10R,13S,14S,17S)-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-carboxylic acid; 4-Androstene-3-oxo-17-beta-carboxylic acid | 7385-78-6 | C20H28O3 | 详情 | 详情 |
| (II) | 18977 | (8S,9S,10R,13S,14S,17S)-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-carbonyl chloride | C20H27ClO2 | 详情 | 详情 | |
| (III) | 22446 | 2,5-bis(trifluoromethyl)phenylamine; 2,5-bis(trifluoromethyl)aniline | 328-93-8 | C8H5F6N | 详情 | 详情 |
| (IV) | 22447 | (8S,9S,10R,13S,14S,17S)-N-[2,5-bis(trifluoromethyl)phenyl]-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-carboxamide | C28H31F6NO2 | 详情 | 详情 | |
| (V) | 22448 | 3-((3S,3aS,5aS,6R,9aS,9bS)-3-[[2,5-bis(trifluoromethyl)anilino]carbonyl]-3a,6-dimethyl-7-oxododecahydro-1H-cyclopenta[a]naphthalen-6-yl)propionic acid | C27H31F6NO4 | 详情 | 详情 | |
| (VI) | 22449 | (4aR,4bS,6aS,7S,9aS,9bS)-N-[2,5-bis(trifluoromethyl)phenyl]-4a,6a-dimethyl-2-oxo-2,3,4,4a,4b,5,6,6a,7,8,9,9a,9b,10-tetradecahydro-1H-indeno[5,4-f]quinoline-7-carboxamide | C27H30F6N2O2 | 详情 | 详情 | |
| (VII) | 22450 | (4aR,4bS,6aS,7S,9aS,9bS,11aR)-N-[2,5-bis(trifluoromethyl)phenyl]-4a,6a-dimethyl-2-oxohexadecahydro-1H-indeno[5,4-f]quinoline-7-carboxamide | C27H32F6N2O2 | 详情 | 详情 |