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Route Optimization of PF-07059013 (7)

有机合成与工艺文献分享 2025-03-18 07:15
文章摘要
本文研究了PF-07059013的合成路线优化，特别是在Pd2dba3-tBuXPhos系统中Pd黑沉淀的问题。研究发现，使用预复合催化剂如tBuXPhos Pd G3可以显著提高反应速率并减少Pd黑沉淀。通过高通量筛选，确定了tBuBrettPhos、RockPhos和Me4tBuXPhos等配体能够有效抑制不希望的C-N偶联反应。最终，tBuBrettPhos Pd G6溴化物被证明是最稳定和高效的催化剂。此外，研究还探讨了亲核试剂的选择对反应的影响，并提出了通过质子化吡唑部分来减少其与过渡金属结合能力的策略。
Route Optimization of PF-07059013 (7)
查看文献： Route Optimization of the Noncovalent Modulator of Hemoglobin PF-07059013 for Treatment of Sickle Cell Disease through a Palladium-Mediated C–O Coupling, Part II: Pilot Plant Scale Manufacture
查看期刊：Organic Process Research & Development
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