2026-10-13T18:54:49Z https://www.scidb.cn/oai

10.57760/sciencedb.39246 2026-06-11T15:21:22Z

2026-06-11 Improved Synthetic Process of Tradipitant doi:10.57760/sciencedb.39246 en ABSTRACT: This study focuses on improving the synthesis process of the neurokinin-1 (NK-1) receptor antagonist Tradipitant (1). To address the production safety and environmental risks associated with highly toxic, malodorous, or hazardous reagents used in existing routes (such as thiophenol, n-butyllithium, and sodium azide), this study developed a safer and greener new synthetic route. The route starts from 2-chloropyridine and, through optimization of key steps, achieves improvements: replacing thiophenol with sodium phenylsulfinate to prepare intermediate 4, using lithium diisopropylamide (LDA) instead of n-butyllithium for α-sulfonyl substitution coupling, and azidotrimethylsilane (TMSN3) instead of sodium azide to prepare azide intermediate 8. The improved process conditions are milder, significantly reduce safety risks, and increase the overall yield from 44.5% reported in the literature to 49.1% (based on 9), while also enhancing the quality and yield of key intermediates, making it more suitable for industrial production requirements. tradipitant; NK1 receptor antagonist; anti-dizziness effect; synthetic process huang jiang chi Sun Yan Li Fei Liu Daosheng Li Xingzhou PUBLIC https://creativecommons.org/licenses/by-sa/4.0/ dataset Science Data Bank