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.
Shilcrat
Susan C.
SC
Synthetic Chemistry Department, Chemical R&D, SmithKline Beecham Pharmaceuticals, P.O. Box 1539, King of Prussia, Pennsylvania 19406.
Mokhallalati
Mohamed K.
MK
Fortunak
Joseph M. D.
JM
Pridgen
Lendon N.
LN