2-Amino-5-bromo-4-methyl-3-nitropyridine

Part A:; A reaction vessel was purged with inert gas. All steps were performed under inert gas protection. The vessel was then charged with 7.50 L of acetic acid at 20-25° C. Next, 1.00 kg of the compound of formula 1 was added to the vessel. A yellow suspension was formed. This was followed by the addition of 1.07 kg of sodium acetate. A very thick, yellow suspension was formed and the reaction was noted to be slightly exothermic. The temperature was raised to about 27° C. The mixture was then cooled to about 15-20° C. and a sample was taken for high pressure liquid chomatography (HPLC) monitoring. A solution of 1.15 kg of bromine (1.1 eq.) and 2.5 L of acetic acid was prepared. A 10/11 portion of the solution, i.e., 1.0 eq. at 15-20° C. was added to the vessel over about 10-15 minutes. The addition was slightly exothermic and some cooling was necessary (TA reaction vessel was purged with inert gas. All steps were performed under inert gas protection. The vessel was then charged with 7.50 L of acetic acid at 20-25° C. Next, 1.00 kg of the compound of formula 1 was added to the vessel. A yellow suspension was formed. This was followed by the addition of 1.07 kg of sodium acetate. A very thick, yellow suspension was formed and the reaction was noted to be slightly exothermic. The temperature was raised to about 27° C. The mixture was then cooled to about 15-20° C. and a sample was taken for high pressure liquid chromatography (HPLC) monitoring. A solution of 1.15 kg of bromine (1.1 eq.) and 2.5 L of acetic acid was prepared. A 10/11 portion of the solution, i.e., 1.0 eq. at 15-20° C. was added to the vessel over about 10-15 minutes. the addition was slightly exothermic and some cooling was necessary (TTo a solution of 4-methyl-3-nitropyridin-2-amine (25 g, 163 mmol) in AcOH (250 ml) was added NaOAc (26.7 g, 326 mmol) and cooled to 15-20°C. Bromine (78.24 g, 489 mmol) in AcOH (200 ml) was added over 30 min and stirred at room temperature for a period of 2 h. The reaction mixture was poured into ice water, the solid formed was filtered and dried to afford title compound as a yellow solid (32 g, 84 percent); 1H NMR (400 MHz, DMSO-dNitric acid (0.7 ml) was added dropwise to a solution of 5-bromo-4-methylpyridine-2-amine (2.0 g) in concentrated sulfuric acid (8.7 ml) at 55 C. over 30 minutes, and the mixture was stirred at the same temperature for 3 hours. After further stirring at room temperature for 2 hours, the reaction solution was poured into ice water. A 50% aqueous sodium hydroxide solution was added, and the resulting precipitate was collected by filtration, washed with distilled water and then dried under reduced pressure to give the title compound (2.5 g).MS (ESI) m/z: 268 (M+H)+.1H-NMR (CDCl3) delta: 2.54 (3H, s), 5.83 (2H, brs), 8.29 (1H, s).