American Chemical Society
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Synthesis of Imatinib by C–N Coupling Reaction of Primary Amide and Bromo-Substituted Pyrimidine Amine

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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 Liu
A 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.