3-Aminoisonicotinic acid (3.55 g, 25.7 mmol) was added with concentrated sulfuric acid (2.5 ml) and methanol (50 ml), and the reaction was heated to reflux at 80°C for 3 days. After completion of the reaction, methanol was removed by evaporation and the residue was diluted with deionized water (75 ml) and heated to 80 °C. Solid sodium carbonate was added slowly until no gas was produced. The reaction mixture was cooled to room temperature and extracted with dichloromethane (2 x 100 ml). The organic phases were combined, dried with anhydrous magnesium sulfate, filtered and concentrated to give methyl 3-aminoisonicotinate as a beige solid (2.36 g, 60% yield). The product was characterized by 1H NMR (500 MHz, DMSO-d6): δ 8.24 (1H, s), 7.74 (1H, d, J=5.3 Hz), 7.46 (1H, d, J=5.2 Hz), 6.67 (2H, brs), 3.83 (3H, s). The mass spectrum (ES+) showed the molecular ion peak m/z 153 ([M+H]+).
