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Skeletal Editing of Pyrimidines to Pyrazoles by Formal Carbon Deletion.

ABSTRACT: A method for the conversion of pyrimidines into pyrazoles by a formal carbon deletion has been achieved guided by computational analysis. The pyrimidine heterocycle is the most common diazine in FDA-approved drugs, and pyrazoles are the most common diazole. An efficient method to convert pyrimidines into pyrazoles would therefore be valuable by leveraging the chemistries unique to pyrimidines to access diversified pyrazoles. One method for the conversion of pyrimidines into pyrazoles is known, though it proceeds in low yields and requires harsh conditions. The transformation reported here proceeds under milder conditions, tolerates a wide range of functional groups, and enables the simultaneous regioselective introduction of N-substitution on the resulting pyrazole. Key to the success of this formal one-carbon deletion method is a room-temperature triflylation of the pyrimidine core, followed by hydrazine-mediated skeletal remodeling.

SUBMITTER: Bartholomew GL

PROVIDER: S-EPMC10353523 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Skeletal Editing of Pyrimidines to Pyrazoles by Formal Carbon Deletion.

Bartholomew G Logan GL Carpaneto Filippo F Sarpong Richmond R

Journal of the American Chemical Society 20221128 48

A method for the conversion of pyrimidines into pyrazoles by a formal carbon deletion has been achieved guided by computational analysis. The pyrimidine heterocycle is the most common diazine in FDA-approved drugs, and pyrazoles are the most common diazole. An efficient method to convert pyrimidines into pyrazoles would therefore be valuable by leveraging the chemistries unique to pyrimidines to access diversified pyrazoles. One method for the conversion of pyrimidines into pyrazoles is known, t ...[more]

PMID: 36441940

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