Synthesis of DP-IV inhibitor MK-0431

ORGN 667

Michele E. Kubryk, Michele_Kubryk@merck.com1, Karl Hansen1, Jaume Balsells1, Yi Xiao1, Nelo Rivera2, Eugenia Njolito1, Bryon Simmons1, Feng Xu1, and Joseph D. Armstrong III1. (1) Department of Process Research, Merck Research Laboratories, 126 East Lincoln Avenue, Rahway, NJ 07065, (2) Process Research, Merck Research Laboratories, P.O.Box 2000, Rahway, NJ 07065
The DP-IV inhibitor, MK-0431, is a new treatment for type II diabetes currently being evaluated in clinical studies. Two different syntheses of MK-0431, developed by MRL Process Research, will be presented. The first route consists of coupling the triazole fragment 3 with chiral amino acid 2. The stereogenic center of 2 is established via Noyori asymmetric reduction of a ketoester. The second route, which is currently used to prepare MK-0431, consists of installing the stereogenic center of 1 in the final chemical step via a catalytic asymmetric reduction of enamine amide 4, which is prepared in a three step through-process from an aryl carboxylic acid precursor.


Asymmetric Reactions, Heterocycles, Aromatics, Combinatorial, and Physical Organic Chemistry
8:00 PM-10:00 PM, Wednesday, 31 August 2005 Washington DC Convention Center -- Hall A, Poster

8:00 PM-10:00 PM, Monday, 29 August 2005 Washington DC Convention Center -- Hall A, Sci-Mix

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005