ACS Publications Industry Webinar

Development of an Improved Process for a Key Sotorasib Intermediate

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Watch a webinar recording featuring Amanda Stahl, a process chemist at Amgen, as she unveils the fascinating journey behind the development of the second-generation process for producing rac-4, a key intermediate in the manufacture of Sotorasib.

Through innovation, the improved process has achieved remarkable results:

97% reduction in organic solvent usage
71% reduction in wastewater generation

Whether you're deep in the lab or leading process development, this session presents actionable insights for process chemists aiming to enhance sustainability and boost efficiency—particularly in drug manufacturing.

Don’t miss this opportunity to elevate your expertise, connect with fellow process chemists, and spark fresh inspiration for your own projects.

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SPEAKER INFORMATION

Amanda Stahl

Process Development Sr. Associate | DST Synthetics | Amgen

Amanda Stahl is a Process Development Senior Associate at Amgen, specializing in small molecule and hybrid modality process development. She focuses on advancing efficient and sustainable approaches to drug substance manufacturing, most recently developing a second-generation, more environmentally friendly synthesis for a key Sotorasib intermediate.

Beyond her role at Amgen, Amanda is dedicated to inspiring the next generation of scientists. She teaches undergraduate chemistry as an adjunct faculty member at Pepperdine University, infusing her courses with practical, real-world applications. She earned her B.S. in Chemistry from Pepperdine University and her M.S. from Ohio University.

RESEARCH SPOTLIGHT

Development of an Improved Process To Prepare a Key Intermediate in the Manufacture of Sotorasib

Org. Process Res. Dev. 2025, 29, 6, 1456–1464

https://doi.org/10.1021/acs.oprd.5c00043

Sotorasib is a first-in-class KRAS^G12C inhibitor with a unique carbon–nitrogen atropisomer. Described herein is the development of an improved second-generation process to manufacture a key sotorasib intermediate, rac-4. Notable improvements to the second-generation process include the development of a three-step fully telescoped sequence in acetonitrile and the use of phosgene as an isocyanating agent, which allowed for dichloromethane, aqueous extractive work-ups, and distillations to be completely removed from the process. Compared to the first-generation process, these process improvements led to a 97% reduction in organic solvent usage and a 71% reduction in wastewater generation and still maintains a 75% yield and >99.5% purity of rac-4 in the overall process.

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