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【结 构 式】 
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【药物名称】M-30 【化学名称】(4aalpha,5beta,8aalpha)-N-(Decahydro-2-methyl-5-isoquinolinyl)-3,4,5-trimethoxybenzamide 【CA登记号】19590-85-3 【 分 子 式 】C20H30N2O4 【 分 子 量 】362.4731 |
【开发单位】Aventis Pharma (Originator) 【药理作用】Antiarrhythmic Drugs, CARDIOVASCULAR DRUGS |
合成路线1
The reduction of 5-nitro-2-methylisoquinolinium p-toluenesulfonate (I) with H2 over PtO2 in acetic acid H2SO4 gives 5-amino-2-methyldecahydroisoquinoline (II), which is acetylated with acetic anhydride in DMF and submitted to fractionated crystallization to give cis-5,9,10-H-5-acetamido-2-methyldecahydroisoquinoline (III). Hydrolysis of (III) with H2SO4 in refluxing water yields cis-5,9,10-H-5-amino-2-methylisoquinoline (IV), which is finally acylated with 3,4,5-trimethoxybenzoyl chloride (V) by means of KHCO3 in benzene.
| 【1】 Peters, E.R.; Marthinson, I.W.; Fowler, S.J.; Lawson, J.W.; Gueldner, R.C.; The stereochemistry of 5-substituted decahydroisoquinolines and their antiarrhythmic activity. J Med Chem 1968, 11, 5, 997. |
| 【2】 Mathison, I.W. (Aventis Pharmaceuticals, Inc.); Benzamido 2 lower alkyl decahydroisoquinolines. DE 1900948; FR 2004748; GB 1246051; JP 7114060; US 3674791 . |
| 【3】 Sneddon, J.; M-30 and M-32. Drugs Fut 1985, 10, 3, 202. |
| 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) | 29055 | 2-methyl-5-nitroisoquinolinium phenylmethanesulfonate | C17H16N2O5S | 详情 | 详情 | |
| (II) | 29056 | 2-methyldecahydro-5-isoquinolinamine | C10H20N2 | 详情 | 详情 | |
| (III) | 29057 | N-[(4aS,5R,8aS)-2-methyldecahydro-5-isoquinolinyl]acetamide | C12H22N2O | 详情 | 详情 | |
| (IV) | 29058 | (4aS,5R,8aS)-2-methyldecahydro-5-isoquinolinamine | C10H20N2 | 详情 | 详情 | |
| (V) | 13571 | 3,4,5Ttrimethoxybenzoyl chloride | 4521-61-3 | C10H11ClO4 | 详情 | 详情 |