Synthesis of the Impurities of Dabigatran Etexilate Mesylate
GAO Hang1,3， ZONG Xin-jie2,3， CHEN Hui-hui3， LIU Chang-ying3， WANG Song-hui3， LI Chuan3， XU Wei-ren3
1. Graduate school, Tianjin Medical University, Tianjin 300070, China; 2. Graduate school, Tianjin University of Chinese Traditional Medicine, Tianjin 300193, China; 3. Tianjin Key Laboratory of Molecular Design and Drug Discovery， Tianjin Institute of Pharmaceutical Research Co., Ltd, Tianjin 300193, China
Abstract：According to the synthetic route of dabigatran exetilate mesylate, seven kinds of impurities were synthesized: 3-【【【2-｛［(4-cyanophenyl)amino］methyl｝-1-methyl-1H-benzimidazol-5-yl】carbonyl】pyridin-2-ylamino】propionic acid(A), ethyl 3-【【【2-【｛［4-(ethoxy) tertiary amine］phenyl｝amino】methyl】-1-methyl-1H-benzimidazol-5-yl］carbonyl】pyridin-2-ylamino】propanoate hydrochlorid(B), ethyl 3-【【【2-【｛［(4-N′-methylcarbamimidoyl)phenyl］amino｝methyl】-1-methyl-1H-benzimidazol-5-yl】carbonyl】pyridin-2-ylamino】propanoate hydrochlorid(C), methyl 3-【【【2-【【【4-｛［(hexyloxy)carbonyl］carbamimidoyl｝phenyl】amino】methyl】-1-methyl-1H-benzimidazol-5-yl】carbonyl】(pyridin-2-yl)amino】propanoate hydrochlorid(D), ethyl 3-【【【2-【【【4-【｛［(hexyloxy)carbonyl］amino｝carbonyl】phenyl】amino】methyl】-1-methyl-1H-benzimidazol-5-yl】carbonyl】(pyridin-2-yl)amino】propanoate(E), 3-【【【2-【【【4-｛［(hexyloxy)carbonyl］carbamimidoyl｝phenyl】amino】methyl】-1-methyl-1H-benzimidazol-5-yl】-carbonyl】(pyridin-2-yl)amino】propanoic acid(F), ethyl (Z)-3-【【【2-【【【4-{［(N,N′-bishexyloxy)carbonyl］carbamimidoyl｝phenyl】amino】methyl】-1-methyl-1H-benzimidazol-5-yl】carbonyl】(pyridin-2-yl)amino】propanoate(G). The structures were confirmed by 1H NMR and ESI-MS.
2015, Vol. 23 
