Parallel synthesis of bis-heterocyclic isoxazolylmethyl- And isoxazolinylmethylpyrazoles

The solution-phase parallel synthesis of a 136-member library of isoxazol(in)e-CH₂-pyrazoles is described, X-ray crystallographic structure determination verified the regioselectivities of the N-alkylation and nitrile oxide 1,3-dipolar cycloaddition steps. The construction of these pharmaceutically relevant heterocycles on solid support under microwave irradiation is also demonstrated. The resulting library of drug-like compounds has been added to the National Institutes of Health repository (∼10 mg of each with ≥90% purity) for pilot-scale biomedical studies with bioassay data available at the National. Center for Biotechnology Information PubChem database. A subset of these compounds has been broadly screened by Dow AgroSciences for herbicidal, fungicidal, and insecticidal activity.