100367-40-6

6635-86-5

100367-40-6

Part A: The reaction vessel was first purged with inert gas under inert gas protection. 7.50L of acetic acid was added to the vessel and the temperature was maintained at 20-25°C. Subsequently, 1.00 kg of 4-methyl-3-nitropyridin-2-amine (compound of formula 1) was added to form a yellow suspension. Next, 1.07 kg of sodium acetate was added and the reaction mixture changed to a very thick yellow suspension and a slight exothermic phenomenon was observed. After raising the reaction temperature to about 27°C, the reaction was cooled to 15-20°C and samples were taken for analysis by high pressure liquid chromatography (HPLC). A solution of 1.15 kg of bromine (1.1 eq.) with 2.5 L of acetic acid was prepared and a 10/11 portion (i.e., 1.0 eq.) was added dropwise to the reaction vessel over a period of 10-15 minutes, maintaining the temperature at 15-20°C. A slight exotherm was observed during the dropwise addition and proper cooling was required to maintain the temperature not exceeding 20°C. HPLC analysis was performed immediately after dropwise addition and monitored again after 60 minutes and less than 10% of the starting material was found to be remaining. The remaining bromine solution was added and the reaction was continued with stirring for 30-60 minutes until the reaction was complete. At the end of the reaction, 10.0 L of ice water was added and cooled to 11°C to form a suspension. After continued stirring for 30-60 minutes, the product was collected by filtration and washed with 3 x 2.50 L of ice water. The product was dried at 40°C to constant weight to give 1.45 kg of yellow crystals in 96% yield. The melting point of the product was 132 °C. IR (KBr, cm^-1): 1633, 1581, 1538, 1512, 1458, 1377, 1344, 1321, 1244, 869, 779. 1H-NMR (CDCl3, δ, ppm): 2.55 (s, 3H), 5.85 (bs, 2H), 8.25 (s, 1H) .13C-NMR (CDCl3, δ, ppm): 20.81, 112.14, 144.49, 151.91, 153.78 (2C).MS (M+1): 232.Elemental Analysis: C6H6BrN3O2 Calculated Values: C, 31.05; H, 2.60; N, 18.11; Br, 34.43.Measured Values. 30.95; H, 2.42; N, 17.45; Br, 34.80.