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【结 构 式】 
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【分子编号】65866 【品名】2-bromo-8-fluoro-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-one 【CA登记号】 |
【 分 子 式 】C11H8BrFN2O 【 分 子 量 】283.0998032 【元素组成】C 46.67% H 2.85% Br 28.22% F 6.71% N 9.9% O 5.65% |
合成路线1
该中间体在本合成路线中的序号：(III)Reductive cyclization of 6-fluoro-3-(2-nitroethyl)-1H-indole-4-carboxylic acid methyl ester (I) by means of Zn and HCl in methanol/water gives 8-fluoro-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-one (II), which is brominated by means of Pyr/HBr/Br2 in THF/dichloromethane to afford the 2-bromo derivative (III). Condensation of the brominated compound (III) with 4-formylphenylboronic acid (IV) by means of Pd(PPh3)4 and Na2CO3 in refluxing H2O/ethanol/toluene provides 8-fluoro-2-(4-formylphenyl)-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-one (V), which is finally reductocondensed with methylamine (VI) by means of NaBH4 (1). Scheme 1.
| 【1】 Webber, S.E., Thoresen, L.H., Tikhe, H., Canan-Koch, S.S. (Agouron Pharmaceuticals, Inc.; Cancer Research UK). Tricyclic inhibitors of poly(ADP-ribose) polymerases. CA 2360003, EP 1140936, JP 2002534523, US 6495541, WO 2000042040. |
| 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) | 65864 | 6-fluoro-3-(2-nitroethyl)-1H-indole-4-carboxylic acid methyl ester | C12H11FN2O4 | 详情 | 详情 | |
| (II) | 65865 | 8-fluoro-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-one | C11H9FN2O | 详情 | 详情 | |
| (III) | 65866 | 2-bromo-8-fluoro-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-one | C11H8BrFN2O | 详情 | 详情 | |
| (IV) | 61564 | 4-Formylphenylboronic acid; 4-Formylbenzeneboronic acid; 4-Boronobenzaldehyde; Benzaldehyde-4-boronic acid; 4-Formylphenylboronic acid | 87199-17-5 | C7H7BO3 | 详情 | 详情 |
| (V) | 65867 | 8-fluoro-2-(4-formylphenyl)-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-one | C18H13FN2O2 | 详情 | 详情 | |
| (VI) | 11021 | Methanamine; Methylamine | 74-89-5 | CH5N | 详情 | 详情 |