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Development of a scalable atroposelective process to MRTX1719-an inhibitor of the PRMT5*MTA complex

By Cheng Yi Chen, Ph.D. Chemical Processing R&D, Mirati Therapeutics, San Diego, CA 92130, USA chenc@mirati.com A new approach to stereopure atropisomeric molecules is enabled by a continuous flow-crystallization process. Continuous accumulation of the product under its optimal crystallization conditions is combined with a parallel synthetic process occurring within its own optimal regime. Therefore, in a holistic sense, this approach constitutes an asymmetric synthesis via dynamic kinetic resolution (DKR). The application of Simultaneous Processing of Antagonistic Chemical Events methodology (SPACE) will be showcased on a densely functionalized active pharmaceutical ingredient (MRTX1719) for which significant yield improvement (from 60% to 85%) was realized on >10 kg scale.
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