PILOT-SCALE SYNTHESIS OF A NOVEL NONPEPTIDE ANGIOTENSIN-II RECEPTOR ANTAGONIST

FR143187 is a novel nonpeptide angiotensin II receptor antagonist unde r development at Fujisawa Pharmaceutical Co. for the treatment of hype rtension, Development of a process for preparation on a large scale is described. The optimized process is 10 steps in length and uses only commercially available materials for each step. Efficient methylation of the 2-position of a pyrrole derivative was achieved by reduction of a Mannich base via the quaternary ammonium salt, Selective cyanation directed by a soh:ent effect was also investigated. Process improvemen t efforts focused on optimized reaction conditions for each step, lead ing to a high-quality product according to a new and concise synthetic route.