title: Regioselective synthesis of 1,4-disubstituted imidazoles.
abstract: A short and efficient synthesis of 1,4-disubstituted imidazoles has been developed which provides the desired products with complete regioselectivity. This protocol allows preparation of compounds which are challenging to prepare by current literature methods in a regioselective fashion, a sterically and electronically diverse range of N-substituents being accessible. The sequence involves an unusual double aminomethylenation of a glycine derivative, to yield a 2-azabuta-1,3-diene, onto which addition of an amine nucleophile results in a transamination/cyclization to prepare the substituted imidazole. The cyclization event is surprisingly insensitive to steric and electronic variations on the amine component, enabling a diverse range of imidazoles to be prepared.
authors.affiliation: Chemical Development, Bristol-Myers Squibb Company, 1 Squibb Drive, New Brunswick, New Jersey 08903, USA. Michael.Schmidt@bms.com
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schmidt
authors.forename: Martin D
authors.initials: MD
authors.lastname: Eastgate
mesh_terms: D060326:Chemistry Techniques, Synthetic; D003500:Cyclization; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D007093:Imidazoles