抗糖尿病药物利格列汀中间体合成中同分异构体杂质的结构表征  

Characterization of Isomeric Impurities in the Intermediate of Anti-diabetes Drug Linagliptin

作　　者：马卉芳 谢建伟 MA Hui-fang;XIE Jian-wei(School of Medicine&Health Sciences,Guangzhou Huashang College,Guangzhou 511300,China;College of Chemistry and Bioengineering,Hunan University of Science and Engineering,Yongzhou 425199,China)

机构地区：[1]广州华商学院健康医学院,广东广州511300 [2]湖南科技学院化学与生物工程学院,湖南永州425199

出　　处：《精细化工中间体》2023年第4期68-74,共7页Fine Chemical Intermediates

基　　金：湖南省自然科学基金资助项目(2021JJ30290)。

摘　　要：合成利格列汀中间体8-溴-7-(2-丁炔-1-基)-3,7-二氢-3-甲基-1-[(4-甲基-2-喹唑啉基)甲基]-1H-嘌呤-2,6-二酮(3)时,获得2个O-苄基同分异构体杂质A和B。其结构经HRMS、^(1)H NMR、^(13)C NMR、^(1)H-^(1)H COSY、^(1)H-^(13)C HSQC和^(1)H-^(13)C HMBC表征与结构确证,同时对其生成过程的机理进行了推理。为利格列汀原料药生产过程中杂质的监控提供了有益参考。Two O-benzylated isomeric impurities A and B were obtained during the preparation of intermediate 3 of Linagliptin.These two O-benzylated isomers were characterized by HRMS,^(1)H NMR,^(13)C NMR,^(1)H-^(1)H COSY,^(1)H-^(13)C HSQC,and ^(1)H-^(13)C HMBC.The structure of the two impurities was confirmed and the formation mechanism of these two compounds was also proposed.The results are beneficial for the monitoring of impurities in the production process of Linagliptin.

关 键 词：利格列汀中间体 O-苄基化异构体 药物杂质 核磁共振波谱 

分 类 号：O482.53[理学—固体物理]