The process development of a novel aldose reductase inhibitor, FK366. Part 1. Improvement of discovery process and new syntheses of 1-substituted quinazolinediones

This contribution describes part 1 of process development of a novel aldose reductase inhibitor FK366 (1). The original process applied on a laboratory scale was improved from the safety viewpoint to manufacture materials on 500-L scale suitable for toxicological and pharmacological evaluations. A new process, including regioselective alkylation of silylated quinazolinedione, provided a practical and cost-effective synthesis of FK366 in a dramatically increased yield.