Pilot-Plant Preparation of an αvβ3 Integrin Antagonist: Process Development of a Carbonyldiimidazole Peptide Coupling

The process development of a peptide coupling with CDI is discussed. Various solvents, addition orders, stoichiometries, and reaction temperatures were investigated. A reliable crystallization procedure was also developed. The new process was piloted to provide 342 kg of product in two batches with an average 85% yield and 99% assay.