In this paper (Gonzalez et al., Org. Process Res. Dev. 2019, 23, 6, 1143-1151) from the Chemical and Synthetic Development team at Bristol-Myers Squibb, DoE and QbD methodologies have been used to develop a telescoped process for the API step in the route to a reversible inhibitor of BTK. (Scheme 1) Scheme 1: Two step

Whereas process parameter risk quantification is conducted using mathematical calculations (Monte Carlo simulations) based on a process model, risk analysis is a semi-subjective methodology, of value for both early, as well as for late process development work. Herein we will focus on early process development, when little experimental information is available. In spite of its