General procedure for the synthesis of 2-methyl-5-nitronicotinic acid from ethyl 2-methyl-5-nitronicotinate: compound D4 (300 g, 1.4 mol) was dissolved in a mixture of 800 mL hydrochloric acid and 800 mL water. The reaction mixture was heated under reflux conditions for 1 hour. Upon completion of the reaction, it was cooled to room temperature, the reaction solution was diluted with 2.0 L of water and slowly neutralized with the addition of solid sodium bicarbonate to pH=5.0. During this process, a precipitate was gradually formed. The mixture was further cooled and the precipitate was collected by filtration. After drying, brown solid D5 (223 g, 85.7% yield) was obtained. The product was characterized by 1H NMR (DMSO-d6, 300 MHz): δ = 2.84 (s, 3H), 8.74-8.75 (d, 1H), 9.35-9.36 (d, 1H), 13.90 (s, 1H).LC-MS analysis showed that the [M-1]+ peak was located at 180.9.
