A mixture of 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (93.6% purity, 16.16 g, 50.0 mmol), 6-chloro-8-methyl-2,4-dihydro-1H-3,1-benzoxazine-2,4-dione (99.0% purity, 11.22 g, 52.5 mmol), and 3-methylpyridine (16.5 mL. 15.8 g, 170 mmol) were added slowly and dropwise to an acetonitrile (15 mL) solution of methanesulfonyl chloride (5.0 mL, 7.4 g, 65 mmol) in acetonitrile (65 mL) at -5 °C. The reaction mixture was stirred at -5 to 0 °C for 15 minutes before being warmed to 50 °C and maintained for 4 hours. Subsequently, the reaction system was cooled to room temperature, water (29 mL) was added slowly and dropwise, and stirring was continued for 15 minutes. Next, 40% aqueous methylamine solution (20.0 mL, 17.9 g, 231 mmol) was added all at once and stirred overnight at room temperature. After completion of the reaction, the mixture was filtered, and the solid was washed sequentially with 2:1 acetonitrile-water (2 × 30 mL) and pure acetonitrile (3 × 30 mL), and dried under nitrogen protection to afford the target product, 3-bromo-N-(4-chloro-2-methyl-6-(methylcarbamoyl)phenyl)-1-(3-chloro-pyridin-2-yl)-1H-pyrazole-5-carboxamide, as a light yellow powder, 22.44 g (HPLC purity 95.5%, yield calculated based on purity 88.7%). The structure of the product was confirmed by 1H NMR (CDCl3): δ 2.18 (s, 3H), 2.95 (s, 3H), 6.21 (m, 1H), 7.10 (s, 1H), 7.24 (m, 2H), 7.39 (m, 1H), 7.80 (d, 1H), 8.45 (d, 1H).
