Development of Adagrasib’s Commercial Manufacturing Route

13 December 2022, Version 1

Abstract

A commercial route to MRTX849 (adagrasib) was developed to support clinical and commercial needs. Yield was improved to 32% over six chemical steps. A doubly regioselective SNAr reduced consumption of an expensive chiral intermediate, reaction optimization led to parts per million palladium catalysis, and a new method to deprotect Cbz-groups were developed to mitigate risk associated with benzyl iodide.

Keywords

KRAS-G12C
oncology
targeted covalent inhibitor
active pharmaceutical ingredient

Supplementary materials

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Description
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Supporting Information
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Experimentals and compound characterization
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