反应详情

温度

60 °C

To a solution of ethyl 2-(2-bromo-5-fluoroisonicotinoyl)-3-(dimethylamino)acrylate (Intermediate 66, 0.690 g, 2 mmol, 1 equiv.) in THF (7 mL) was added 1-methylazetidin-3-amine HCl (245 mg, 2 mmol, 1 equiv.) and potassium carbonate (276 mg, 2 mmol, 1 equiv.). This reaction mixture was stirred at 60° C. for 1 h. The reaction mixture was concentrated under reduced pressure and re-suspended in DMF (7 mL). Potassium carbonate (553 mg, 4 mmol, 2 equiv.) was added, and the reaction mixture was stirred at 70° C. for 3 h. The reaction mixture was cooled to room temperature and quenched with water. 1 N HCl was added until pH 4-5 was reached. The precipitate was washed with water and hexanes and dried to provide ethyl 6-bromo-1-(1-methylazetidin-3-yl)-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylate (1.2 g, ≧99%). Calcd for C15H16BrN3O3 [M+H]+: 367.91.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. stirringthe reaction mixture was stirred at 70° C. for 3 h
3. temperatureThe reaction mixture was cooled to room temperature
4. customquenched with water
5. addition1 N HCl was added until pH 4-5
6. washThe precipitate was washed with water and hexanes
7. customdried