A short and efficient synthesis of valsartan via a Negishi reaction

Abstract

An efficient synthesis of the angiotensin-II inhibitor valsartan (Diovan®) is presented. Directed ortho-metalation of 5-phenyl-1-trityl-1H-tetrazole (6) and its Negishi coupling with aryl bromide 5 are the key steps of the synthesis. This method overcomes many of the drawbacks associated with previously reported syntheses.