Abstract
The initial process development of the novel beta-lactamase inhibitor WCK 6395 is described. All key intermediates were readily isolated by either crystallization or precipitation to eliminate related impurities. Seven possible process-related impurities were hypothesized, and initial control strategies were implemented. Additionally, process parameters were identified and improved to decrease or circumvent these impurities. The parameters of each step were optimized through prior knowledge and experimentation to improve yield and desired quality of WCK 6395 to support toxicological studies. The improved process effectively reduced the use of hazardous reagents, was robust on the kilogram scale, demonstrated at the pilot scale, and subsequently served as the basis for commercial route development.