Supporting Information. In the published version, partial tabulation and spectral information for compounds 3a, 8b, 17, 20, 23, and S54 were missing because an earlier version of the Supporting Information was inadvertently published. A new version of the Supporting Information that contains all of this information is provided herein.

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.

The selective modification of nitrogen heteroaromatics enables the development of new chemical tools and accelerates drug discovery. While methods that focus on expanding or contracting the skeletal structures of heteroaromatics are emerging, methods for the direct exchange of single core atoms remain limited. Here, we present a method for 14N → 15N isotopic exchange for several aromatic nitrogen heterocycles. This nitrogen isotope transmutation occurs through activation of the heteroaromatic substrate by triflylation of a nitrogen atom, followed by a ring-opening/ring-closure sequence mediated by 15N-aspartate to effect the isotopic exchange of the nitrogen atom. Key to the success of this transformation is the formation of an isolable 15N-succinyl intermediate, which undergoes elimination to give the isotopically labeled heterocycle. These transformations occur under mild conditions in high chemical and isotopic yields.