Snapdragon Chemistry Fortunate to Collaborate with Amgen on Publication in OPR&D
Waltham, MA – August 25, 2022 – In this collaboration with Amgen, we describe the development and kilogram-scale demonstration of a high-temperature continuous-flow racemization process to recycle the off-enantiomer of an atropisomeric sotorasib intermediate.
In this article, we describe the development and kilogram-scale demonstration of a high-temperature continuous-flow racemization process to recycle the off-enantiomer of an atropisomeric sotorasib intermediate. Part 1 of this two-part series details the design and execution of a classical resolution to generate atropisomer M-1 from a racemic precursor (rac-1). In parallel, the team sought to develop a racemization process to enable recycling of the classical resolution waste stream and maximize productivity and sustainability. Computational and experimental methods revealed a high barrier to rotation (ca. 42 kcal/mol) prompting the design of a high-temperature (>300 °C) racemization protocol for recovery of the racemic compound. Described herein are the determination of the barrier to rotation, optimization of conditions to enable racemization, proof-of-concept for a continuous-flow process to execute the process, and kilogram-scale demonstration, including (1) recovery of the undesired atropisomer as a crystalline solid from the classical resolution waste stream, (2) thermal racemization by a high-temperature continuous-flow process, and (3) isolation of the racemic compound by crystallization directly from the reaction stream.
About Snapdragon Chemistry
Snapdragon Chemistry specializes in active pharmaceutical ingredient (API) batch and continuous flow process development, utilizing state-of-the-art automation technology and proprietary equipment to solve complex process and analytical development challenges. With R&D and manufacturing headquartered in Waltham, Massachusetts, Snapdragon’s 70+ employees come with strong ties to the local scientific community, with 31 PhD scientists on staff. For more information, please contact firstname.lastname@example.org.