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

Abstract 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 Pd 2 dba 3 and XANTPHOS in the presence of excess Cs 2 CO 3 afforded good yields of the coupled products. Subsequent reduction and cyclization of these intermediates provided the desired benzimidazole compounds.