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Synthesis of a Highly Functionalized Quinazoline Organozinc

有机合成与工艺文献分享 2025-11-11 08:21
文章摘要
本文研究背景为开发高功能化喹唑啉有机锌试剂的合成工艺，该试剂是实施阻转选择性Negishi反应的关键起始原料。研究目的旨在解决传统金属-卤素交换工艺中存在的副反应和中间体不稳定性问题，通过系统优化反应条件建立稳健的连续流生产工艺。研究结论表明：通过精确控制反应温度（-70°C至10°C）和停留时间（≥60秒），可有效抑制异丙基杂质7的生成；结合FTIR在线监测与Dynochem过程建模，成功实现了从实验室到生产规模的工艺放大；最终采用管式反应器与连续搅拌釜反应器的组合方案，解决了无机盐析出导致的设备堵塞问题，为喹唑啉类有机锌试剂的工业化生产提供了可靠方案。
Synthesis of a Highly Functionalized Quinazoline Organozinc
查看文献： Synthesis of a Highly Functionalized Quinazoline Organozinc toward KRAS G12C Inhibitor Divarasib (GDC-6036), Enabled through Continuous Flow Chemistry
查看期刊：Organic Process Research & Development
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