This paper describes the development of a practical, efficient and reproducible preparation of ASK1 inhibitor GS-4997 (Selonsertib). Our efforts were committed to designing and developing a novel synthetic strategy. The novel route involved high-yielding preparation of 5-(4-cyclopropyl-1H-imidazole-1-yl)-2-fluoro-4-methylbenzoic acid (5) through adjusting reaction sequence, and the one-pot procedure for the synthesis of 6-(4-isopropyl-4H-1,2,4-triazol-3-yl) pyridin-2-amine (7). The developed process provided an overall yield of 45.8%, which enabled us to rapidly synthesize multi-gram quantities of GS-4997 in 99.3% purity.

Graphical Abstract

中文翻译：

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GS-4997 的多克级合成，细胞凋亡信号调节激酶 1 的抑制剂

本文介绍了一种实用、高效且可重复的 ASK1 抑制剂GS-4997 (Selonsertib) 制剂的开发。我们的努力致力于设计和开发一种新颖的合成策略。该新路线通过调整反应顺序高产制备5-(4-环丙基-1H-咪唑-1-基)-2-氟-4-甲基苯甲酸( 5 )，一锅法制备6-(4-isopropyl-4 H -1,2,4-triazol-3-yl) pyridin-2-amine ( 7 ) 的合成。开发的工艺提供了 45.8% 的总产率，这使我们能够以 99.3% 的纯度快速合成数克数量的GS-4997 。

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