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Early Process Development of CH7057288 (1)

有机合成与工艺文献分享 2025-02-17 07:39
文章摘要
本文介绍了CH7057288的早期工艺开发过程，CH7057288是一种选择性靶向NTRK阳性癌症的神经酪氨酸受体激酶（NTRK）抑制剂。研究背景源于在开发alectinib过程中检测到含有苯并呋喃结构的杂质16，推测其通过两次连续的SNAr反应形成。研究目的是探索利用这一副反应作为合成CH7057288的主要反应。文章详细描述了CH7057288的合成路线，并指出在Friedel-Crafts反应中，N-(叔丁基)酰胺基团在酸性条件下不稳定，导致叔丁基断裂形成酰胺25和腈26两种杂质。遗憾的是，这些关键杂质无法在结晶过程中去除，最终仍存在于药物物质中。研究结论表明，抑制这些关键杂质的形成仍是一个挑战。
Early Process Development of CH7057288 (1)
查看文献： Early Process Development of CH7057288, a Benzofuran-Containing Selective NTRK Inhibitor
查看期刊：Organic Process Research & Development
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