Recently, GSK’772 emerged as a highly potent receptor-interacting protein-1 (RIP1) kinase inhibitor with broad therapeutic potential.  The initial supply route for GSK’772A was sufficiently designed for speed of execution, with a highly telescoped front end that required chromatography of a late stage intermediate in order to produce high quality API.  While this approach was suitable for early pre-clinical toxicology studies and clinical supply, it was did not meet our criteria for a long-term manufacturing process.  As such, our strategy commenced with new route exploration to identify the most direct method to construct the API from commodity chemicals followed by implementation of new and enabling technologies to ensure process robustness and sustainability.  Herein, we wish to share a story of the design and execution of the new manufacturing process for GSK’772, highlighted by efficient construction of the benzoxazapine core and an innovative approach to attach the triazole subunit.  The newly developed manufacturing process features a short synthetic sequence from commodity materials, high overall yield, and significant reduction in process mass intensity (PMI).

The design and development of a manufacturing process for GSK’772

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.