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.
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