Synthesis of 4-substituted pyrazole-3,5-diamines via Suzuki–Miyaura coupling and iron-catalyzed reduction?

Organic & Biomolecular Chemistry Pub Date: 2017-11-16 DOI: 10.1039/C7OB02373A

Abstract

A general and efficient synthesis of 4-substituted-1H-pyrazole-3,5-diamines was developed to access derivatives with an aryl, heteroaryl, or styryl group, which are otherwise relatively difficult to prepare. The first step is based on the Suzuki–Miyaura cross-coupling reaction utilizing the XPhos Pd G2 precatalyst. The coupling reactions of 4-bromo-3,5-dinitro-1H-pyrazole with the electron-rich/deficient or sterically demanding boronic acids enabled the production of the corresponding dinitropyrazoles. The subsequent iron-catalyzed reduction of both nitro groups with hydrazine hydrate accomplished the synthesis. The additional demethylation of the 4-methoxystyryl derivative allowed the production of the carboanalog of CAN508 reported as a selective CDK9 inhibitor.

Graphical abstract: Synthesis of 4-substituted pyrazole-3,5-diamines via Suzuki–Miyaura coupling and iron-catalyzed reduction
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