A commercial route to adagrasib (1) was developed to support clinical and commercial needs. Yield was improved to 32% over six chemical steps. A doubly regioselective S_NAr reduced consumption of a 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.

中文翻译：

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Adagrasib商业化生产路线的开发

阿达格拉西布 ( 1 )的商业途径已开发出来以支持临床和商业需求。通过六个化学步骤，产率提高到 32%。双区域选择性 S _N Ar 减少了手性中间体的消耗，反应优化导致了百万分之一的钯催化，并开发了一种脱保护 Cbz 基团的新方法以降低与苄基碘相关的风险。