Elziverine, Ro-224839
依齐维林Chemical Name: 1-(3,4-Dimethoxybenzyl)-6,7-dimethoxy-4-[4-(2-methoxyphenyl)piperazin-1-ylmethyl]isoquinoline
CAS No. 95520-81-3
项目整合开发状态: Phase II
项目研究机构: Roche (Originator)
合成路线: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.
📌 参考资料/链接：
参考文献标题:Substd.isoquinolines
文献作者:Bruderer,H.; Kierstead,R.W.; Mullin,J.G.Jr.; Nakamura,K.; O'Brien,J.P.; Sidney,T.; Tateishi,M.(F.Hoffmann-La Roche AG)
参考来源:EP 0126480; ES 8601141; JP 1984222478; US 4544657
📄 详细内容
合成路线: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.
参考文献标题:Elziverine
文献作者:Castar,J.; Prous,J.
参考来源:Drugs Fut 1988,13(2),120
产品链接: CAS No. 95520-81-3››