Evolution of the Process for the Preparation of a Selective ErbB VEGF Receptor Inhibitor.

An efficient synthetic route to the potent and selective ErbB VEGF receptor inhibitor, BMS-690514 (1) is described. Strategic modifications in both approach and procedure addressed several issues, which led to a safe, efficient, and economical process for the preparation of multi-kilogram quantities of 1. The convergent route involves alkylation of a suitably protected (3R,4R)-4-aminopiperidin-3-ol with the triethyl(alkyl)ammonium salt of a functionalized pyrrolotriazine 3a followed by deprotection to provide 1 as the crystalline free base. [ABSTRACT FROM AUTHOR]