title: A New Regioselective Synthesis of 1,2,5-Trisubstituted 1H-Imidazoles and Its Application to the Development of Eprosartan.
abstract: 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.
authors.affiliation: Synthetic Chemistry Department, Chemical R&D, SmithKline Beecham Pharmaceuticals, P.O. Box 1539, King of Prussia, Pennsylvania 19406.
authors.forename: Susan C.
authors.initials: SC
authors.lastname: Shilcrat
authors.forename: Mohamed K.
authors.initials: MK
authors.lastname: Mokhallalati
authors.forename: Joseph M. D.
authors.initials: JM
authors.lastname: Fortunak
authors.forename: Lendon N.
authors.initials: LN
authors.lastname: Pridgen