Parallel Synthesis of 1H-Pyrazolo[3,4‑d]pyrimidines via Condensation of N‑Pyrazolylamides and Nitriles

A novel parallel medicinal chemistry (PMC)-enabled synthesis of 1H-pyrazolo­[3,4-d]­pyrimidines employing condensation of easily accessible N-pyrazolylamides and nitriles has been developed. The presented studies describe singleton and library enablements that allowed rapid generation of molecular diversity to examine C4 and C6 vectors. This chemistry enabled access to challenging alkyl substituents, expanding the overall chemical space beyond that available via typical C­(sp2)–C­(sp2) coupling and SNAr transformations. Furthermore, monomer group interconversions allowing the use of larger and more diverse amides and carboxylic acids as precursors to nitriles are discussed.