Efficient synthesis of losartan, a nonpeptide angiotensin II receptor antagonist

Article abstract of DOI:10.1021/jo00100a048

A highly efficient, convergent approach to the synthesis of the angiotensin II receptor antagonist losartan (1) is described. Directed ortho-metalation of 2-trityl-5-phenyltetrazole provides the key boronic acid intermediate 10 for palladium-catalyzed biaryl coupling with bromide 5 obtained from the regioselective alkylation of the chloroimidazole 2. This methodology overcomes many of the drawbacks associated with previously reported syntheses.