Improved synthetic route of 4-[4-(3,4-methylenedioxyphenyl)-5-(2-pyridyl)-1H-imidazol-2-yl]benzamide

Aim To improve the synthetic procedure of the ALK5 inhibitor 4-[4-(3,4-methylene dioxyphenyl)-5-(2-pyridyl)-1H-imidazol-2-yl]benzamide(SB-431542).Methods The key intermediate 4-[4-(3,4-methylenedioxyphenyl)-5-(2-pyridyl)-N-1-hydroxyl-imidazol-2-yl]benzonitrile(1)was reduced with (Ti(Ⅲ))Cl_3 to give 4-[4-(3,4-methylenedioxyphenyl)-5-(2-pyridyl)-1H-imidazol-2-yl]benzonitrile(2).The cyano group of compound 2 was converted to amide by hydrolysis with KOH power in t-BuOH to give the SB-431542.Result and conclusion The ()~1H-NMR and MS data of the intermediates and the end product were identical to that in literature.This improved synthetic route is simpler,more efficient and convenient,its additional merits are furnishing more pure product and avoiding the usage of toxic reagent P(OEt)_3.