Pyridine-to-Pyridazine Skeletal Editing

Nitrogen-containing heterocycles underpin many pharmaceuticals, where subtle atomic rearrangements can markedly alter efficacy and safety. Pyridines are ubiquitous scaffolds in pharmaceuticals, yet their close analogues, pyridazines with two adjacent ring nitrogens, remain underexplored owing to limited synthetic access. Here, we report a skeletal editing strategy that converts pyridines into pyridazines by replacing one ring carbon with nitrogen while preserving aromaticity. The sequence comprises N-amine assembly, followed by an m-chloroperoxybenzoic acid (mCPBA)-mediated ring-remodeling sequence proceeding via a 1,2-diazatriene intermediate to effect carbon-to-nitrogen substitution. The two-step process is operationally simple, runs at ambient temperature in air, and requires no UV irradiation or preinstalled groups. The method shows broad functional-group tolerance, including complex, drug-derived molecules, providing rapid, scalable access to pyridazines. This platform expands heterocyclic chemical space and enables late-stage diversification for drug discovery.