Concentrated sulfuric acid (96%, 144 mL, 2.69 mol, 18.6 eq.) was slowly added dropwise to a stirred suspension of 2-aminonicotinic acid (20.0 g, 0.145 mol) in methanol (228 mL, 7.12 mol, 49.2 eq.), and the reaction system was kept at 0 °C. Subsequently, the reaction mixture was irradiated in a microwave reactor (power input 300 W) at 60 °C and atmospheric pressure for 1.5 hours. Upon completion of the reaction, the light brown mixture was carefully poured into ice water, maintained at 0 °C, and solid sodium carbonate was added by batchwise addition until complete neutralization (pH > 8). The aqueous layer was extracted three times with ethyl acetate. The organic layers were combined, washed sequentially with saturated brine and deionized water, and then dried with anhydrous magnesium sulfate. Finally, the organic solvent was evaporated to afford methyl 2-aminopyridine-3-carboxylate (21.15 g, 93% yield) as colorless needle-like crystals with purity meeting the analytical requirements.
