维格列汀中间体的合成工艺改进  

Improved synthesis process of a vildagliptin intermediate

作　　者：江澜 李毓飞 张立 蔡林宏 官晓书 胡湘南[2] JIANG Lan;LI Yu-fei;ZHANG Li;CAI Lin-hong;GUAN Xiao-shu;HU Xiang-nan(College of Environment and Resources,Chongqing Technology and Business University,Chongqing 400067,China;School of Pharmacy,Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆工商大学环境与资源学院,重庆400067 [2]重庆医科大学药学院,重庆400016

出　　处：《中国药物化学杂志》2021年第4期280-285,共6页Chinese Journal of Medicinal Chemistry

基　　金：重庆市科委资助项目(cstc2019jscx-msxmX0096)。

摘　　要：目的制备维格列汀的重要中间体(S)-1-(2-氯乙酰基)吡咯烷-2-甲腈,并对其合成工艺进行优化。方法以L-脯氨酸为原料,先经无溶剂条件下氯乙酰化反应,再经氨基甲酸乙酯和氯化亚砜反应合成得到(S)-1-(2-氯乙酰基)吡咯烷-2-甲腈,并应用星点设计-效应面法优化合成工艺。结果 (S)-1-(2-氯乙酰基)吡咯烷-2-甲腈的结构经IR、^(1)H-NMR、^(13)C-NMR和MS确正。结论该合成路线具备原料价格便宜、步骤较少、操作简单等优点,具有实际的应用价值。The synthesis process of the important intermediate of vildagliptin,(S)-1-(2-chloroacetyl)pyrro-lidine-2-carbonitrile was optimized.And the intermediate was prepared from L-proline via chloroacetylation, amidation and dehydration.The process was optimized by the central composite design-response surface methodology.The improved synthetic route has advantages of lower raw materials cost, fewer reaction steps and simple operation, and owns important application value.

关 键 词：维格列汀 (S)-1-(2-氯乙酰基)吡咯烷-2-甲腈 星点设计-效应面法 工艺优化 

分 类 号：R914[医药卫生—药物化学]