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。
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.
出处
《中国现代应用药学》
CAS
CSCD
2015年第9期1090-1093,共4页
Chinese Journal of Modern Applied Pharmacy
关键词
甲磺酸达比加群酯
降解杂质
合成
dabigatran etexilate mesylate
degradation of impurity
synthesis