Expeditious process to CETP inhibitor candidate PF-03185043

ORGN 707

Brian Chekal, Roberto Colon-Cruz, Arun Ghosh, Brian P Jones, Danny G. Lafrance, Brett M. Lillie, Christopher N. McElwee, Jade D. Nelson, and Lulin Wei. Chemical Research and Development, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340
Development and optimization of an effective third-generation process to PF-03185043, a CETP inhibitor targeted for the treatment of hypoalphalipoproteinemia, is described. Highlights of this process include a high yielding Friedel-Crafts reaction to access a key quinolone intermediate, a high yielding reduction / acylation / oxidation sequence, and a highly diastereoselective reductive amination to incorporate the desired tetrazole.