|
【结 构 式】 
|
【药物名称】Icopezil maleate, CP-118954-11, CP-118954 【化学名称】3-[2-(1-Benzylpiperidin-4-yl)ethyl]-6,7-dihydro-5H-pyrrolo[3,2-f]-1,2-benzisoxazol-6-one maleate salt (1:1) 【CA登记号】145815-98-1, 145508-78-7 (free base) 【 分 子 式 】C27H29N3O6 【 分 子 量 】491.54868 |
【开发单位】Pfizer (Originator) 【药理作用】Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, Acetylcholinesterase Inhibitors |
合成路线1
The Friedel Crafts condensation of 6-methoxyindolin-2-one (I) with acetyl chloride and AlCl3 gives the 5-acetyl-6-methoxyindolin-2-one (II), which is treated with hydroxylamine and acetic anhydride to yield the O-acetyloxime (III). The cyclization of (III) affords the 3-methyl-6,7-dihydro-5H-isoxazolo[4,5-f]indol-6-one (IV), which is condensed with 4-(iodomethyl)piperidine-1-carboxylic acid tert-butyl ester (V) to provide the adduct (VI). Finally this compound is deprotected with TFA and benzylated with benzyl bromide (VII) to furnish the target compound.
| 【1】 Maggi, A.; Brufani, M.; Lappa, S.; Filocamo, L.; New acetylcholinesterease inhibitors. Drugs Fut 1997, 22, 4, 397. |
| 【2】 Villalobos, A.; et al.; 5, 7-Dihydro-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-6H-pyrrolo[3,2-f]-1,2-benzisoxaxol-6-one: A potent and centrally-selective inhibitor of acetylcholinesterase with an improved margin of safety. J Med Chem 1995, 38, 15, 2802. |
| 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) | 41235 | 6-methoxy-1,3-dihydro-2H-indol-2-one | C9H9NO2 | 详情 | 详情 | |
| (II) | 41236 | 5-acetyl-6-hydroxy-1,3-dihydro-2H-indol-2-one | C10H9NO3 | 详情 | 详情 | |
| (III) | 41237 | 5-ethanimidoyl-6-hydroxy-1,3-dihydro-2H-indol-2-one | C12H12N2O4 | 详情 | 详情 | |
| (IV) | 41238 | 3-methyl-5,7-dihydro-6H-isoxazolo[4,5-f]indol-6-one | C10H8N2O2 | 详情 | 详情 | |
| (V) | 41239 | tert-butyl 4-(iodomethyl)-1-piperidinecarboxylate | C11H20INO2 | 详情 | 详情 | |
| (VI) | 41240 | tert-butyl 4-[2-(6-oxo-6,7-dihydro-5H-isoxazolo[4,5-f]indol-3-yl)ethyl]-1-piperidinecarboxylate | C21H27N3O4 | 详情 | 详情 | |
| (VII) | 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 |