| 引用本文: | 李振中,武峥,宋波,刘沫毅.达比加群酯降解杂质的合成[J].中国现代应用药学,2015,32(9):1090-1093. |
| LI Zhenzhong,WU Zheng,SONG Bo,LIU Moyi.Synthesis of the Degradation Impurities of Dabigatran Etexilate Mesylate[J].Chin J Mod Appl Pharm(中国现代应用药学),2015,32(9):1090-1093. |
|
| 摘要: |
| 目的 为了更好的控制甲磺酸达比加群酯的质量，合成达比加群酯的5个降解杂质。方法 以N-[2-[[(4-氰基苯基)氨基]甲基]-1甲基-1H-5-苯并咪唑]羰基]-N-2-吡啶基-β-氨基丙酸乙酯为原料，经过成脒反应、酰胺反应、水解反应制备了杂质A~E。结果 所得产物经1H-NMR，LC-MS和13C-NMR初步确证了结构，收率≥65%。结论 该合成路线反应条件温和，产品纯度高。 |
| 关键词: 甲磺酸达比加群酯 降解杂质 合成 |
| DOI： |
| 分类号:R284.1；R917.101 |
| 基金项目: |
|
| Synthesis of the Degradation Impurities of Dabigatran Etexilate Mesylate |
|
LI Zhenzhong, WU Zheng, SONG Bo, LIU Moyi
|
|
Industrial Engineering Technology Research Center for Oral Soild Preparation of Beijing, China Resources Saike Pharmaceutical Co., Ltd., Beijing 101111, China
|
| Abstract: |
| OBJECTIVE To perform the quality control of dabigatran etexilate mesylate, five degradation impurities recorded in quality specifications are prepared. METHODS Five degradation impurities A-E were synthesized from N-[[2-[[(4-cyanophenyl)amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl]-N-2-pyridinyl-β-alanine ethyl ester, via amidine reaction, amidation reaction and hydrolytic reaction. RESULTS The strutures of five degradation impurities were established by 1H-NMR, LC-MS and 13C-NMR, with yield ≥65%. CONCLUSION The reaction condition is mild, and the purity is high. |
| Key words: dabigatran etexilate mesylate degradation of impurity synthesis |
