A practical enantioselective synthesis of a potent dual PPAR alpha/gamma agonist

ORGN 273

Xinhua Qian, xinhua.qian@bms.com1, Rajendra P. Deshpande, rajendra.deshpande@bms.com2, Erqing Tang3, Junying Fan, junying.fan@bms.com3, Keming Zhu1, Shirley Wong4, Jingyang Zhu3, and Jale Muslehiddinoglu, jale.muslehiddinoglu@bms.com5. (1) Process Research and Development, Bristol-Myers Squibb Pharmaceutical Research Institute, 1 Squibb Drive, P.O. Box 191, New Brunswick, NJ 08903-0191, (2) Process Research And Development, Bristol-Myers Squibb, 1, Squibb drive, New brunswick, NJ 08903, (3) Process R&D, R&D, Bristol-Myers Squibb Company, 1 Squibb Drive, New Brunswick, NJ 08903, (4) Analytical Research and Development, Bristol-Myers Squibb Pharmaceutical Research Institute, One Squibb Drive, P. O. Box 191, New Brunswick, NJ 08903-0191, (5) Process Research and Development, Bristol-Myers Squibb Company, Pharmaceutical Research Institute, One Squibb Drive, New Brunswick, NJ 08903-0191
Target compound 1 is a potent activator of peroxisome proliferator-activated receptors (PPARs). Activation of PPAR alpha/gama receptors results in reduced plasma triglycerides, elevated level of plasma HDL cholesterol, and insulin sensitization in type 2 diabetic patients. This presentation will describe an efficient and practical synthesis of compound 1. The key step in the synthesis involves a chiral auxiliary assisted diastereoselective alkylation of an aldimine to introduce an S-methyl substituted benzylamine functionality in the molecule. Process development and optimization of individual synthetic steps will be presented.

 

Biologically Active Molecules
8:00 AM-12:00 PM, Tuesday, April 8, 2008 Morial Convention Center -- Rm. R05, Oral

Division of Organic Chemistry

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008