Synthesis of a p38 antagonist via a Heck tandem cyclization to form naphthyridinones

ORGN 427

R. J. Cvetovich, raymond_cvetovich@merck.com, John Y. L. Chung, john_chung@merck.com, Mark McLaughlin, mark_mclaughlin@merck.com, Joseph S. Amato, F-R. Tsay, Mark Jensen, Steven Weissman, weissman@merck.com, and Daniel Zewge, Daniel_Zewge@Merck.com. Department of Process Research, Merck Research Laboratories, PO Box 2000; R800-B375, Rahway, NJ 07065
The synthesis of naphthyridinone intermediate 2 used in the synthesis of 3 was achieved via a unique Heck tandem cyclization reaction. By reacting acrylanilides with tri-halosubstituted pyridine 2 using palladium acetate cyclization products are made competitively to Heck or bis-Heck products. A discussion of the optimization this reaction will be presented.

 

Process R&D and Practical Syntheses of Medicinal Agents
1:00 PM-4:40 PM, Tuesday, 12 September 2006 Moscone Center -- Room 132, Oral

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006