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【结 构 式】 
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【分子编号】52503 【品名】8-(methyloxy)-3,4-dihydro-1(2H)-isoquinolinone 【CA登记号】 |
【 分 子 式 】C10H11NO2 【 分 子 量 】177.20288 【元素组成】C 67.78% H 6.26% N 7.9% O 18.06% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Acylation of 3-methoxyphenethyl amine (VI) with methyl chloroformate gave the corresponding carbamate (VII). Intramolecular cyclization of (VII) with hot polyphosphoric acid produced a mixture of isomeric isoquinolinones (VIII) and (IX) from which the desired 6-methoxy isomer (IX) was isolated by column chromatography. Reduction of (IX) with LiAlH4 furnished the tetrahydro isoquinoline (X). Then reductive alkylation of amine (X) with ketone (V) in the presence of NaBH(OAc)3 produced the corresponding cyclohexyl amine as a mixture of cis/trans isomers. The title trans compound was obtained from the reaction mixture by chromatographic separation.
| 【1】 Meagher, K.L.; et al.; Studies towards the next generation of antidepressants. Part 1: Indolylcyclohexylamines as potent serotonin reuptake inhibitors. Bioorg Med Chem Lett 2001, 11, 14, 1885. |
| 【2】 Meagher, K.L.; Mewshaw, R.E. (American Home Products Corp.); Tetrahydroisoquinolinyl-indole derivs. for the treatment of depression. WO 0064886 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 47079 | 3-(4-oxocyclohexyl)-1H-indole-5-carbonitrile | C15H14N2O | 详情 | 详情 | |
| (VI) | 37185 | 2-(3-methoxyphenyl)-1-ethanamine; 3-methoxyphenethylamine | 2039-67-0 | C9H13NO | 详情 | 详情 |
| (VII) | 47076 | methyl 3-methoxyphenethylcarbamate | C11H15NO3 | 详情 | 详情 | |
| (VIII) | 52503 | 8-(methyloxy)-3,4-dihydro-1(2H)-isoquinolinone | C10H11NO2 | 详情 | 详情 | |
| (IX) | 47077 | 6-methoxy-3,4-dihydro-1(2H)-isoquinolinone | C10H11NO2 | 详情 | 详情 | |
| (X) | 47078 | methyl 1,2,3,4-tetrahydro-6-isoquinolinyl ether; 6-methoxy-1,2,3,4-tetrahydroisoquinoline | C10H13NO | 详情 | 详情 |