An improved API step for the formation of an aminopyrimidine-based kinase inhibitor is described. The presence of a reactive acrylamide functional group presented a considerable challenge during scale-up, resulting in side-product formation and low in-process yields for the final S_NAr reaction. Impurity identification guided process development efforts, enabling rapid scale-up of a safe and phase-appropriate process to deliver the API to support toxicology studies.

中文翻译：

---

通过C–N键形成的S _N Ar反应制备共价激酶抑制剂的改进方法

描述了用于形成基于氨基嘧啶的激酶抑制剂的改进的API步骤。反应性丙烯酰胺官能团的存在在按比例放大过程中提出了相当大的挑战，导致副产物形成和最终S _N Ar反应的低过程产率。杂质鉴定指导了工艺开发工作，从而可以快速扩大安全，适合阶段的工艺，以提供API来支持毒理学研究。