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【结 构 式】 
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【药物名称】 【化学名称】5-Chloro-4-isopropoxy-2-methoxy-N-(2-methyl-1,2,3,4-tetrahydro-5-isoquinolinyl)benzamide 【CA登记号】201150-38-1 (monoHCl) 【 分 子 式 】C21H25ClN2O3 【 分 子 量 】388.898 |
【开发单位】GlaxoSmithKline (Originator) 【药理作用】Antiepileptic Drugs, NEUROLOGIC DRUGS |
合成路线1
Quaternization of 5-aminoisoquinoline (I) in acetone afforded isoquinolinium salt (II), which was reduced with NaBH4 to the tetrahydroisoquinoline (III). Alternatively, 5-nitroisoquinoline (IV) was quaternized to give (V) and subsequently reduced with NaBH4 to afford 2-methyl-5-nitro-1,2,3,4-tetrahydroisoquinoline (VI), which was further reduced to amine (III) by catalytic hydrogenation over Pd/C. Amine (III) was finally coupled with acid chloride (VII) in the presence of Et3N to provide the title benzamide).
| 【1】 Harling, J.D.; Thompson, M.; Identification of a series of 1,2,3,4-tetrahydrois. 216th ACS Natl Meet (Aug. 23-27, Boston) 1998, Abst MEDI 099. |
| 【2】 Harling, J.D.; Orlek, B.S.; Thompson, M. (SmithKline Beecham plc); Substd. benzamide derivs. and their use as anticon. EP 0906283; US 6110934; WO 9748683 . |
| 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) | 22799 | 5-isoquinolinylamine; 5-isoquinolinamine | 1125-60-6 | C9H8N2 | 详情 | 详情 |
| (II) | 22800 | 2-methyl-2lambda(5)-isoquinolin-5-ylamine; 2-methyl-2lambda(5)-isoquinolin-5-amine | C10H12N2 | 详情 | 详情 | |
| (III) | 22801 | 2-methyl-1,2,3,4-tetrahydro-5-isoquinolinylamine; 2-methyl-1,2,3,4-tetrahydro-5-isoquinolinamine | C10H14N2 | 详情 | 详情 | |
| (IV) | 22802 | 5-nitroisoquinoline | 607-32-9 | C9H6N2O2 | 详情 | 详情 |
| (V) | 22803 | 2-methyl-5-nitro-2lambda(5)-isoquinoline | C10H10N2O2 | 详情 | 详情 | |
| (VI) | 22804 | 2-methyl-5-nitro-1,2,3,4-tetrahydroisoquinoline | C10H12N2O2 | 详情 | 详情 | |
| (VII) | 22805 | 5-chloro-4-isopropoxy-2-methoxybenzoyl chloride | C11H12Cl2O3 | 详情 | 详情 |