(543a) Development and De-Risking of a Green, Drug Substance Intermediate Process Using Data-Rich Experimentation

A case study is presented describing the development of a green, robust process to produce a drug substance intermediate as an isolated solid. In the first-generation process, the intermediate was telescoped to the subsequent step as a free base solution. The new process improves upon the purity, the process mass intensity (PMI), the reproducibility, and the robustness. The process encompasses multiple Green Chemistry principles, including safer solvents and renewable feedstocks, and the development was expedited by incorporating mathematical modeling and data-rich experimentation into the workflow. This presentation will focus on the experimentation and modeling required to identify appropriate reaction, workup, crystallization, and isolation conditions.