A New Regioselective Synthesis of 1,2,5-Trisubstituted 1H-Imidazoles and Its Application to the Development of Eprosartan

A new method is presented for the preparation of 1,2-disubstitued-1H-imidazole-5-carboxaldehydes by the reaction of N-monosubstituted amidines with 2-halo-3-alkoxy-2-propenals. The reaction is highly regioselective with ratios of 1,2,5:1,2,4-imidazolecarboxaldehydes ranging from 85:15 to 100:0. This methodology could be extended with similar results to the synthesis of imidazole-5-nitriles by the reaction of 2-bromo-3-methoxy-2-propenenitrile with N-monosubstituted amidines.