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【结 构 式】 
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【分子编号】21865 【品名】ethyl 1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydro-4-isoquinolinecarboxylate 【CA登记号】 |
【 分 子 式 】C23H27NO6 【 分 子 量 】413.47052 【元素组成】C 66.81% H 6.58% N 3.39% O 23.22% |
合成路线1
该中间体在本合成路线中的序号：(IV)The condensation of ethyl 2-(aminomethyl)-2-(3,4-dimethoxyphenyl)acetate (I) with 3,4-dimethoxyphenylacetyl chloride (II) by means of NaOH in hot toluene gives ethyl 2-(3,4-dimethoxyphenyl)-3-(3,4-dimethoxyphenylacetamido)propionate (III), which is cyclized by means of Cl3PO in refluxing acetonitrile yielding ethyl 1-(3,4 dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline-4-carboxylate (IV). Aromatization of (IV) with sulfur at 150 C affords the corresponding isoquinoline derivative (V), which is reduced with sodium bis(2 methoxyethoxy)aluminum hydride in THF to give1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline-4-methanol (VI). The reaction of (VI) with SOCl2 in dichloromethane affords 4-(chloromethyl)-6,7-dimethoxy-1-(3,4-dimethoxybenzyl)isoquinoline (VII), which is finally condensed with 1-(2-methoxyphenyl)piperazine (VIII) by means of triethyl amine in hot DMSO.
| 【1】 Bruderer, H.; Kierstead, R.W.; Mullin, J.G. Jr.; Nakamura, K.; O'Brien, J.P.; Sidney, T.; Tateishi, M. (F. Hoffmann-La Roche AG); Substd. isoquinolines. EP 0126480; ES 8601141; JP 1984222478; US 4544657 . |
| 【2】 Castaner, J.; Prous, J.; Elziverine. Drugs Fut 1988, 13, 2, 120. |
| 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) | 21862 | ethyl 3-amino-2-(3,4-dimethoxyphenyl)propanoate | C13H19NO4 | 详情 | 详情 | |
| (II) | 20594 | 2-(3,4-dimethoxyphenyl)acetyl chloride | C10H11ClO3 | 详情 | 详情 | |
| (III) | 21864 | ethyl 2-(3,4-dimethoxyphenyl)-3-[[2-(3,4-dimethoxyphenyl)acetyl]amino]propanoate | C23H29NO7 | 详情 | 详情 | |
| (IV) | 21865 | ethyl 1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydro-4-isoquinolinecarboxylate | C23H27NO6 | 详情 | 详情 | |
| (V) | 21866 | ethyl 1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-4-isoquinolinecarboxylate | C23H25NO6 | 详情 | 详情 | |
| (VI) | 21867 | [1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-4-isoquinolinyl]methanol | C21H23NO5 | 详情 | 详情 | |
| (VII) | 21868 | 4-(chloromethyl)-1-(3,4-dimethoxybenzyl)-6-methoxy-7-isoquinolinyl methyl ether; 4-(chloromethyl)-1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline | C21H22ClNO4 | 详情 | 详情 | |
| (VIII) | 11882 | 1-(2-Methoxyphenyl)piperazine; Methyl 2-piperazinophenyl ether; 1-(2-Methoxyphenyl)-piperazine | 35386-24-4 | C11H16N2O | 详情 | 详情 |