Palladium catalysis and removal in API synthesis: Key factors for the development of a scaleable Sonogashira coupling

ORGN 464

Tong Xiao1, Sergio Cesco-Cancian2, David C. Palmer2, Mayra B. Reyes2, and Kirk L. Sorgi3. (1) Global Chem Pharm, Chemical Development, Johnson & Johnson Pharmaceutical Research & Development, 1000 US 202 Highway, Box 300, Raritan, NJ 08869, (2) Global Chemical and Pharmaceutical Development, Johnson & Johnson Pharmaceutical Research & Development, 1000 US 202 Highway, Box 300, Raritan, NJ 08869, (3) Global Chem Pharm, Chemical Development, Johnson & Johnson Pharmaceutical Research & Development, LLC, 1000 US 202 Highway, Box 300, Raritan, NJ 08869
Palladium catalysis provides ready access to heterocycles with a wide variety of substitution patterns. This methodology is increasingly important for rapid assembly of the complex heterocycles found in many Active Pharmaceutical Intermediates (API's) and is the subject of continued process research and development. However, to be really effective, a process must also incorporate methodology for removal of residual palladium to levels acceptable in an API. We will describe our work leading to an efficient, high yield Sonogashira coupling to assemble the indole sulfide 3 directly. The process includes no isolated intermediates and a novel precipitation method for palladium removal which was successfully scaled to prepare multi-kilo amounts of final drug substance.

 

Modern Acetylene Chemistry
8:00 PM-10:00 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster

Division of Organic Chemistry

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