2-Cyano-3,5-difluoropyridine

Add [CuI (bisimine-CN)] (10 mol%), sodium cyanide (1.4 equiv), and (if solid) aryl halide (1 equiv, 0.3 mmol) to a dried quartz tube in an Ar-filled glove box equipped with a stir bar. Cover the quartz tube with a diaphragm and add acetonitrile solvent (1.2 mL) via a syringe. Remove the tube from the glove box and reseal it with black vinyl electrical tape. Stir the resulting mixture and irradiate it with light at room temperature for 24 hours. Transfer the mixture to a round-bottom flask using acetone or dichloromethane and concentrate the reaction mixture under reduced pressure. Purify the residue by column chromatography using a mixture of hexane/ethyl acetate, pentane/diethyl ether, or CH2Cl2/methanol to obtain 2-cyano-3,5-difluoropyridine.

Figure 2. Synthetic route of cyano-3,5-difluoropyridine

2-Cyano-3,5-difluoropyridine is a white to Orange to Green powder to crystal.

2-Cyano-3,5-difluoropyridine is a difluorinated cyanopyridine compound exhibiting high electron-withdrawing properties. Consequently, its fluorine substituents readily undergo nucleophilic aromatic substitution reactions. This characteristic renders the compound extensively utilised in pharmaceutical synthesis, electronic materials, and organic synthesis applications.

2-Cyano-3,5-difluoropyridine is a versatile reactant used in the preparation of potent and selective inhibitors of DPP-4 that exhibit an attractive pharmacokinetic profile as antidiabetics.