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Pure Appl. Chem., 2002, Vol. 74, No. 8, pp. 1349-1357

Development of a general process for the synthesis of highly substituted imidazoles

Joseph Sisko* and Mark Mellinger

Synthetic Chemistry, GlaxoSmithKline, 709 Swedeland Road, P.O. Box 1539, UW2820, King of Prussia, PA 19406-0939, USA

Abstract: Several highly substituted imidazoles have been under investigation at GlaxoSmithKline as potential therapies for the treatment of rheumatoid arthritis and have spawned the need for a general synthetic method for their preparation on a multikilogram scale. We describe herein the optimization of a general method for the preparation of aryl-substituted TosMIC reagents and the ease with which they undergo [3+2] cycloadditions with a host of imines, prepared in situ, to generate densely functionalized imidazoles with various substitution patterns in a completely regioselective manner.