Regioselective synthesis of benzimidazole thiophene inhibitors of polo-like kinase 1

A regioselective synthesis of novel 1-(2-thienyl)-benzimidazole inhibitors of polo-like kinase 1 is described. Amination of substituted 2-iodo or -bromo nitrobenzenes with a 2-aminothiophene derivative catalyzed by Pd2dba3 and XANTPHOS in the presence of excess Cs2CO3 afforded good yields of the coupled products. Subsequent reduction and cyclization of these intermediates provided the desired benzimidazole compounds.