Synthesis of the CXCR3 antagonist AMG 487

ORGN 143

Michael G. Johnson, mgjohnso@amgen.com1, An-Rong Li, anrongl@amgen.com1, Jiwen Liu2, Andrew P. Marcus1, Alan X. Huang2, and Julio C. Medina1. (1) Amgen Inc, 1120 Veterans Blvd., South San Francisco, CA 94080, (2) Department of Chemistry, Amgen Inc, 1120 Veterans Blvd, South San Francisco, CA 94114
AMG 487 is a small molecule antagonist of the chemokine receptor CXCR3, a biological target expressed primarily on activated T cells and implicated in a variety of autoimmune diseases. In this poster we outline several synthetic routes to the 8-azaquinazolinone core found in AMG 487 and describe the optimized sequence that was employed to produce kilogram quantities of the final product in 6 steps, in 18% overall yield and >99% chemical and enantiomeric purity.

 

Asymmetric Reactions and Syntheses, Physical Organic Chemistry, Combinatorial Chemistry, Total Synthesis
8:00 PM-10:00 PM, Sunday, 26 March 2006 Georgia World Congress Center -- Ex. Hall B4, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 27 March 2006 Georgia World Congress Center -- Ex. Hall B4, Sci-Mix

Division of Organic Chemistry

The 231st ACS National Meeting, Atlanta, GA, March 26-30, 2006