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Updated: Jul 9, 2025

Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines
Published on: June 23, 2019
Synthesis and vectorial functionalisation of pyrazolo[3,4-c]pyridines
Elizabeth V Bedwell1, Flavio da Silva Emery2, Giuliano C Clososki2
1Department of Chemistry, University of Durham South Road Durham DH1 3LE UK p.g.steel@durham.ac.uk.
Abstract:
Heterocycles are a cornerstone of fragment-based drug discovery (FBDD) due to their prevalence in biologically active compounds. However, novel heterocyclic fragments are only valuable if they can be suitably elaborated to compliment a chosen target protein. Here we describe the synthesis of 5-halo-1H-pyrazolo[3,4-c]pyridine scaffolds and demonstrate how these compounds can be selectively elaborated along multiple growth-vectors. Specifically, N-1 and N-2 are accessed through protection-group and N-alkylation reactions; C-3 through tandem borylation and Suzuki-Miyaura cross-coupling reactions; C-5 through Pd-catalysed Buchwald-Hartwig amination; and C-7 through selective metalation with TMPMgCl.LiCl followed by reaction with electrophiles or transmetalation to ZnCl2 and Negishi cross-coupling. Linking multiple functionalisation strategies emulates a hit-to-lead pathway and demonstrates the utility of pyrazolo[3,4-c]pyridines to FBDD.
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