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Some Issues and Their Solutions in the Process Development

有机合成与工艺文献分享 2025-06-11 06:45
文章摘要
本文主要探讨了在噻唑衍生物4的临床前生产工艺开发过程中遇到的放大问题及其解决方案。背景方面，研究针对原工艺中存在的低重现性和原料可用性问题（如碳酸铯的稀缺性）展开。研究目的旨在通过优化反应条件解决这些放大问题，包括筛选替代碱基、优化反应温度和时间等。结论部分表明，通过使用t-BuONa作为替代碱基、添加EtOH作为共溶剂、调整加料顺序和温度控制等措施，成功解决了反应混合物固化、副产物生成和水解风险等问题，最终实现了工艺的稳健放大。
Some Issues and Their Solutions in the Process Development
查看文献： Some Issues and Their Solutions in the Process Development of Ethyl 2-(4-Aminophenoxy)thiazole-5-carboxylate: A Key Intermediate of P2X3 Antagonist
查看期刊： Organic Process Research & Development
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