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【结 构 式】 
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【分子编号】46740 【品名】2-bromo-1-[(3R,5S,8R,9S,10S,13S,14S,17S)-3-hydroxy-3-(methoxymethyl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]-1-ethanone 【CA登记号】 |
【 分 子 式 】C23H37BrO3 【 分 子 量 】441.44898 【元素组成】C 62.58% H 8.45% Br 18.1% O 10.87% |
合成路线1
该中间体在本合成路线中的序号：(IV)Regioselective addition of dimethylsulfoxonium methylide to 5-alpha-pregnane-3,20-dione (I) gave the epoxide (II). Opening of the epoxide ring of (II) with sodium methoxide produced the hydroxy ether (III). Bromination of (III) with Br2 in the presence of a catalytic amount of HBr afforded bromo ketone (IV). This was then condensed with imidazole (V) in refluxing acetonitrile to furnish the title compound.
| 【1】 Hogenkamp, D.J.; et al.; Synthesis and in vitro activity of 3beta-substituted-3alpha-hydroxypregnan-20-ones: Allosteric modulators of the GABAA receptor. J Med Chem 1997, 40, 1, 61. |
| 【2】 Hogenkamp, D.L. (CoCensys, Inc.); 3alpha-Hydroxy-3beta methoxymethyl-21-heterocycle substd. steroids with anesthetic activity. WO 0066614 . |
| 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) | 46737 | (5S,8R,9S,10S,13S,14S,17S)-17-acetyl-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one | 566-65-4 | C21H32O2 | 详情 | 详情 |
| (II) | 46738 | C22H34O2 | 详情 | 详情 | ||
| (III) | 46739 | 1-[(3R,5S,8R,9S,10S,13S,14S,17S)-3-hydroxy-3-(methoxymethyl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]-1-ethanone | C23H38O3 | 详情 | 详情 | |
| (IV) | 46740 | 2-bromo-1-[(3R,5S,8R,9S,10S,13S,14S,17S)-3-hydroxy-3-(methoxymethyl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]-1-ethanone | C23H37BrO3 | 详情 | 详情 | |
| (V) | 10255 | Imidazole; 1H-Imidazole | 288-32-4 | C3H4N2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)Regioselective addition of dimethylsulfoxonium methylide to 5-alpha-pregnane-3,20-dione (I) gave the epoxide (II). Opening of the epoxide ring of (II) with sodium methoxide produced the hydroxy ether (III). Bromination of (III) with Br2 in the presence of a catalytic amount of HBr afforded bromo ketone (IV). This was then condensed with 6-hydroxyquinoline (V) in the presence of potassium tert-butoxide to furnish the quinolinyl ether (VI). The quinoline ring was then oxidized with m-chloroperbenzoic acid, yielding the title N-oxide.
| 【1】 Hogenkamp, D.J.; et al.; Synthesis and in vitro activity of 3beta-substituted-3alpha-hydroxypregnan-20-ones: Allosteric modulators of the GABAA receptor. J Med Chem 1997, 40, 1, 61. |
| 【2】 Hogenkamp, D.L. (CoCensys, Inc.); 3alpha-Hydroxy-3beta methoxymethyl-21-heterocycle substd. steroids with anesthetic activity. WO 0066614 . |
| 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) | 46737 | (5S,8R,9S,10S,13S,14S,17S)-17-acetyl-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one | 566-65-4 | C21H32O2 | 详情 | 详情 |
| (II) | 46738 | C22H34O2 | 详情 | 详情 | ||
| (III) | 46739 | 1-[(3R,5S,8R,9S,10S,13S,14S,17S)-3-hydroxy-3-(methoxymethyl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]-1-ethanone | C23H38O3 | 详情 | 详情 | |
| (IV) | 46740 | 2-bromo-1-[(3R,5S,8R,9S,10S,13S,14S,17S)-3-hydroxy-3-(methoxymethyl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]-1-ethanone | C23H37BrO3 | 详情 | 详情 | |
| (V) | 46742 | 6-Hydroxyquinoline; 6-quinolinol | 580-16-5 | C9H7NO | 详情 | 详情 |
| (VI) | 46741 | 1-[(3R,5S,8R,9S,10S,13S,14S,17S)-3-hydroxy-3-(methoxymethyl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-(6-quinolinyloxy)-1-ethanone | C32H43NO4 | 详情 | 详情 |