New, Scalable Process for the Preparation of 5-Acetyl-1H-pyrazole-3-carboxylic Acid, a Key Intermediate of Darolutamide

Dedicated to the memory of late Professor Ferenc Fülöp (1952–2021)

Abstract

A new, efficient process for the synthesis of 5-acetyl-1H-pyrazole-3-carboxylic acid, a versatile building block and the key intermediate of darolutamide, using diethyl pyrazole-3,5-dicarboxylate as the starting material is described. Contrary to the synthetic routes known from the literature, this procedure does not employ explosive diazo reagents, moreover it is simple and safe, thereby suitable for scale-up.

Keywords

ester hydrolysis - regioselectivity - drug substance - key intermediate - safety - scalability

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