Development of a Scalable Synthesis of Dipeptidyl Peptidase-4 Inhibitor ABT-279

…, TB Borchardt, KM Engstrom, J Gandarilla…

Index: McDermott, Todd S.; Bhagavatula, Lakshmi; Borchardt, Thomas B.; Engstrom, Kenneth M.; Gandarilla, Jorge; Kotecki, Brian J.; Kruger, Albert W.; Rozema, Michael J.; Sheikh, Ahmad Y.; Wagaw, Seble H.; Wittenberger, Steven J. Organic Process Research and Development, 2009 , vol. 13, # 6 p. 1145 - 1155

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Citation Number: 8

Abstract

A convergent, scalable synthesis of dipeptidyl peptidase-4 inhibitor, ABT-279, has been developed and demonstrated on multikilogram scale. The cis-2, 5-disubstituted pyrrolidine is generated by cyclization of a Boc-amine onto an alkynyl ketone followed by stereospecific reduction of the resulting acyliminium intermediate. The amine coupling partner was prepared by a novel Hofmann rearrangement promoted by 1, 3-dibromo-5, 5- ...