|
【结 构 式】 
|
【药物名称】 【化学名称】2-(4-Fluorophenyl)-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one 【CA登记号】283172-76-9 【 分 子 式 】C17H13FN2O 【 分 子 量 】280.30436 |
【开发单位】Agouron (Originator), Cancer Research UK (Originator) 【药理作用】Antineoplastic Enhancing Agents, Modulators of the Therapeutic Activity of Antineoplastic Agents, ONCOLYTIC DRUGS, Poly(ADP-ribose)polymerase-1 (PARP-1) Inhibitors |
合成路线1
Condensation of methyl indole-4-carboxylate (I) with 2-nitroethyl acetate (II) produced the 3-nitroethyl indole (III). After reduction of the nitro group to amine (IV) using Zn and HCl, cyclization under basic conditions gave rise to lactam (V). Electrophilic bromination of (V) employing pyridinium tribromide furnished (VI). Finally, Suzuki coupling of bromide (VI) with 4-fluorobenzeneboronic acid (VII) yielded the title compound.
| 【1】 Thoresen, L.H.; Webber, S.E.; Tikhe, J.; Canan-Koch, S.S. (Agouron Pharmaceuticals, Inc.; Cancer Research Campaign Technology Ltd.); Tricyclic inhibitors of poly(ADP-ribose) polymerases. EP 1140936; WO 0042040 . |
| 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) | 50446 | Indole-4-carboxylic acid methyl ester | 39830-66-5 | C10H9NO2 | 详情 | 详情 |
| (II) | 50447 | 2-nitroethyl acetate | C4H7NO4 | 详情 | 详情 | |
| (III) | 50448 | methyl 3-(2-nitroethyl)-1H-indole-4-carboxylate | C12H12N2O4 | 详情 | 详情 | |
| (IV) | 50449 | methyl 3-(2-aminoethyl)-1H-indole-4-carboxylate | C12H14N2O2 | 详情 | 详情 | |
| (V) | 50450 | 1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one | C11H10N2O | 详情 | 详情 | |
| (VI) | 50451 | 2-bromo-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one | C11H9BrN2O | 详情 | 详情 | |
| (VII) | 38403 | 4-fluorophenylboronic acid | 1765-93-1 | C6H6BFO2 | 详情 | 详情 |