Practical synthesis of a 5-aryl-1,3-thiazolidine-2,4-dione PPAR agonist

ORGN 77

Michael H. Kress1, M. David Weingarten2, Christopher J. Welch3, Maria Beconi4, David J. Mathre5, and James M. McNamara2. (1) Process Research, Merck Research Laboratories, 466 Devon Park Drive, Mailstop WYN-1, Wayne, PA 19087, (2) Process Research, Merck & Co. Inc, P.O. Box 2000, Rahway, NJ 07065, (3) Process Research, Laboratory Automation & Robotics, Merck and Co., Inc, PO Box 2000, RY800-C362, Rahway, NJ 07065, (4) Preclinical Drug Metabolism, Merck & Co. Inc, P.O. Box 2000, Rahway, NJ 07065, (5) Department of Process Research and the Catalysis and Reaction Discovery and Development Lab, Merck and Co., Inc, PO Box 2000, Rahway, NJ 07065-0900
The thiazolidinedione class of insulin-sensitizing agents have shown great promise for the treatment of Type II (adult-onset) diabetes. These agents are generally believed to be agonists of the peroxisome proliferator-activated receptor (PPAR), and are currently a major focus in the field of antidiabetic therapy. We have developed an efficient synthesis of one such analog racemic 5-{3-[4-phenoxy-2-propylphenoxy)propoxy]phenyl}-1,3-thiazolidine-2,4-dione (1) based on a one-pot, bis-Williamson ether synthesis strategy. In addition we have studied the fidelity of the 5-aryl stereocenter under a variety of chemical and physiochemical conditions.

 

Process R&D
1:00 PM-5:00 PM, Sunday, September 7, 2003 Sheraton New York -- Royal Ballroom B, Oral

Division of Organic Chemistry
The 226th ACS National Meeting, New York, NY, September 7-11, 2003