曲格列汀琥珀酸盐的合成工艺  

Optimized synthetic process of trelagliptin succinate

作　　者：于净平 陈武 朱雪焱 张喜全[2] 常晓辉 刘相奎 

机构地区：[1]中国医药工业总院创新药物与制药工艺国家重点实验室,上海200437 [2]江苏正大天晴药业股份有限公司,南京210038

出　　处：《中国新药杂志》2015年第9期1061-1064,共4页Chinese Journal of New Drugs

摘　　要：目的:确定并优化糖尿病药物曲格列汀琥珀酸盐的合成工艺。方法:以4-氟-2-甲基苯甲酸为原料,经氯代、氨解、脱水、溴代、取代、缩合、脱保护、成盐8步反应得到曲格列汀的琥珀酸盐。结果:本研究革除了文献[3]中高毒性,环境污染大的试剂,革除柱层析,优化了后处理及纯化的方法,通过8步反应合成目标化合物,降低了成本,简化了操作,合成总收率35.8%,纯度99.89%。结论:本方法成本低,操作简单,收率高,适合工业化生产。Objective： To optimize the synthetic process of trelagliptin succinate. Methods： Trelagliptin succinate was synthesized from 4-fluoro-2-methylbenzoic acid via eight steps, including chloro, aminolysis, dehy- dration, bromo, substitution, condensation, deprotection, and finally salifying. Results： Our process abolished the regents that are moderate-severely toxic environmental pollution reported in the primary literature. Meanwhile, the method of purification also abolished column chromatography, which was of lower cost and easier operation. The o- verall yield was 35.8% with a purity of 99.89%. Conclusion： This synthetic process is of easy operation and low cost, and is suitable for industrialization.

关 键 词：曲格列汀琥珀酸盐 合成 DPP-IV抑制剂 

分 类 号：R914.5[医药卫生—药物化学]