Synthesis of the Degradation Impurities of Dabigatran Etexilate Mesylate

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)aminomethyl-1-methyl-1H-benzimidazol-5-ylcarbonyl-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.