伊伐布雷定的合成工艺改进  

Improved synthesis of ivabradine

作　　者：叶晓娟[1] 吴勇[1] 廖守主[1] 钱珊[1] 

机构地区：[1]四川大学华西药学院,四川成都610041

出　　处：《中国药物化学杂志》2010年第2期106-109,共4页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(29972013)

摘　　要：目的改进伊伐布雷定的合成工艺。方法以3,4-二甲氧基苯甲醛为起始原料,经溴代、缩合、还原、脱羧、环合、氢化、拆分、水解、氯甲酸乙酯保护、还原得到(1S)-4,5-二甲氧基-1-(甲基氨基甲基)-苯并环丁烷(11),将11与苯并氮杂部分(12)进行偶合,得到目标化合物伊伐布雷定。结果与结论目标化合物结构经1H-NMR谱和质谱确证。通过改进合成目标化合物的反应试剂和后处理方法等,使反应操作简单,易于纯化,适合于工业化生产,总产率由7.8%提高到12.9%。Aim To improve the synthetic procedure of ivabradine.Methods 3,4-Dimethoxybenzaldehyde was used as the starting material to give（1S）-4,5-dimethoxyl-1-（methylaminomethyl）benzocyclobutane（11） by bromination,condensation,reduction,decarboxylation,cyclization,hydrogenation,resolution,hydrolysis,ethyl chlorformate protection and reduction.Then the target compound was obtained by the condensation of 11 and 12.Results and conclusion The structure of the target compound was confirmed by 1H-NMR,MS.The proportion of the ingredients and the method of the postprocessing had been improved in the process of synthesis of the target compound.The improved syntheic way is convenient and might be applied to the industrial manufacture with the increased overall yield from 7.8% to 12.9%.

关 键 词：伊伐布雷定 合成 偶合 

分 类 号：TQ463.2[化学工程—制药化工]