Route Selection and Process Development of a Multikilogram Route to the Inhaled A_(2a) Agonist UK-432,097

摘要

This article describes the selection, process development, and scale-up of a synthetic route to a complex nucleoside analogue, the A_(2a) agonist UK-432,097 (1), that culminated in the manufacture of over 25 kg of the API. The key steps in the process were (1) a stereoselective glycosidation reaction; (2) a scalable bleach-TEMPO oxidation; and (3) an unusual elevated temperature crystallization process for the final API. The problems that were encountered with the scale-up of the route together with how they were overcome are also presented.