Development of a large-scale stereoselective process for novel CETP inhibitors

ORGN 138

Bruce Bechle, bruce.m.bechle@pfizer.com1, Michael Castaldi, michael.j.castaldi@pfizer.com2, Mary Didiuk, mary.didiuk@pfizer.com1, Ryan Kelley, ryan.m.kelley@pfizer.com1, David Whritenour3, Michael R. Makowski4, David A. Perry, David_A_Perry@groton.pfizer.com4, and Thomas A. Brandt3. (1) Medicinal Chemistry, Pfizer Inc, eastern point rd, Groton, CT 06340, (2) Chemical Research and Development, Pfizer Inc, Eastern Point Rd, Groton, CT 06340, (3) Chemical Research and Development, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, (4) Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340
Inhibition of CETP has been identified as a strategy to increase HDL-C levels. To date, several CETP inhibitors have been reported in the literature. We will describe the large scale preparation of two closely related inhibitors 1a & 1b. The original synthesis was twelve steps and was not amendable to scale up due to safety concerns. As a result, we developed an innovative five step convergent process for these compounds starting from the same advanced ketone intermediate 2. The new route provided multi-gram quantities of a stable mesylate salt form and removed the need for chromatography.

 

Physical Organic Chemistry, Combinatorial and Process Chemistry, New Reactions and Methodology, Peptides, Proteins and Amino Acids
8:00 PM-10:00 PM, Sunday, April 6, 2008 Morial Convention Center -- Hall A, Poster

Division of Organic Chemistry

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