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Synthesis of Imatinib by C–N Coupling Reaction of Primary Amide and Bromo-Substituted Pyrimidine Amine
journal contribution
posted on 2019-08-14, 15:34 authored by Cuiling Wang, Xiao Bai, Rui Wang, Xudong Zheng, Xiumei Ma, Huan Chen, Yun Ai, Yajun Bai, Yifeng LiuA new
method for imatinib synthesis is described by using the C–N
coupling reaction of 4-(4-methylpiperazine-1-methyl)benzamide with N-(5-bromo-2-tolyl)-4-(3-pyridyl)pyrimidin-2-amine to form
imatinib. In this synthetic route, the high efficiency and high selectivity
of nano-ZnO as a catalyst is key to the mild hydrolysis of 4-(4-methylpiperazine-1-methyl)benzonitrile
into the corresponding amide. The total imatinib yield was 51.3%,
and the purity was 99.9%. This simple and effective synthetic pathway
avoids gene-impurity production (as classified by the FDA Center for
Drug Evaluation and Research), and the synthesis is environmentally
friendly with a short reaction time.