Using 2-amino-6-bromopyridine (25.90 g, 150 mmol) and trimethylsilylacetylene (22.10 g, 225 mmol) as raw materials, under argon protection, a PdCl2[PPh3]2 (3.50 g, 5 mmol), CuI (2.90 g, 15 mmol), triethylamine (TEA, 70 mL) and benzene (150 mL) The mixture was stirred at 50 °C for 7 hours. After completion of the reaction, it was cooled to room temperature and concentrated under vacuum. The resulting residue was purified by column chromatography (silica gel as stationary phase and EtOAc/hexane as eluent) to give a mixture of 6-((trimethylmethylsilyl)ethynyl)pyridin-2-amine and 6-ethynylpyridin-2-amine. The mixture was dissolved in THF (150 mL) and a THF solution (150 mL) of 1 M TBAF was added slowly dropwise at -20 °C. After dropwise addition, the reaction mixture was stirred at 0 °C for 20 min, followed by dilution with water and extraction with DCM. The organic layer was dried with anhydrous Na2SO4 and concentrated under reduced pressure. Finally, the residue was purified by column chromatography (silica gel as stationary phase and EtOAc/hexane as eluent) to afford the target product 6-ethynylpyridin-2-amine (11.90 g, 67% yield, two-step reaction) as a gray solid.
