抗阿尔茨海默病药物盐酸多奈哌齐的合成  

Synthesis of Donepezil Hydrochloride for Alzheimer’s Disease

作　　者：胡昆[1] 谢宇轩 任杰[1] HU Kun;XIE Yu-xuan;REN Jie(School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou 213164, China)

机构地区：[1]常州大学制药与生命科学学院,江苏常州213164

出　　处：《合成化学》2021年第4期308-314,共7页Chinese Journal of Synthetic Chemistry

基　　金：江苏省研究生科研与实践创新计划项目(SJCX19_0633)。

摘　　要：以4-哌啶甲酸为原料,经酯化、烷基化、酯水解、酰化、脱水和还原反应合成中间体N-苄基-4-哌啶甲醛8;再以3,4-二甲氧基苯甲醛为原料,经缩合、还原、分子内环化反应合成中间体5,6-二甲氧基-1-茚酮9;最后中间体8和中间体9经缩合、还原反应后成盐合成了抗阿尔茨海默病药物盐酸多奈哌齐,总收率56.8%,其结构经^(1)H NMR和^(13)C NMR确证。该路线具有原料廉价易得、操作简便、反应条件温和、后处理简便、收率较高等优点。The intermediate N-benzyl-4-piperidinecarboxaldehyde(8)was synthesized through esterification,alkylation,ester hydrolysis,acylation,dehydration and reduction using 4-piperidinecarboxylic acid as the raw material.Then intermediate 5,6-dimethoxy-1-indanone(9)was synthesized through condensation,reduction and intramolecular cyclization using 3,4-di methoxybenzaldehyde as the raw material.Finally,intermediate 8 and intermediate 9 undergo condensation and reduction reactions to form a salt to obtain donepezil hydrochloride.The total yield was 56.8%.The structure was confirmed by ^(1)H NMR and ^(13)C NMR.The synthetic route has the advantages of cheap and easily obtained raw materials,simple operation,mild reaction conditions,simple post-treatment,and good yield,and has a high industrial production prospect.

关 键 词：4-哌啶甲酸 3 4-二甲氧基苯甲醛 缩合 盐酸多奈哌齐 合成 阿尔茨海默病 制药 

分 类 号：O62[理学—有机化学] R914.5[理学—化学]