反应详情

温度

60 °C

To a solution of ethyl 2-(5-bromo-2-fluoronicotinoyl)-3-(dimethylamino)acrylate (Intermediate 3, 784 mg, 2.27 mmol) dissolved in THF (12 mL) was added (1-methylpiperidin-4-yl)methanamine (291 mg, 2.27 mmol). The reaction mixture was stirred at 60° C. for 2 h, then cooled to room temperature, concentrated under reduced pressure, and the resulting residue was resuspended in DMF (12 mL). Potassium carbonate was added (942 mg, 6.81 mmol, 3 equiv.) to the suspension, and the reaction was stirred at 70° C. for 18 h. The reaction mixture was cooled to room temperature then quenched with 1 N HCl. The reaction mixture was partitioned between water (15 mL) and dichloromethane (15 mL) and the layers were separated. The aqueous layer was extracted with dichloromethane (2×15 mL), and the combined organic layers were concentrated to provide ethyl 6-bromo-1-((1-methylpiperidin-4-yl)methyl)-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (945 mg, >99%).

1. temperaturecooled to room temperature
2. concentrationconcentrated under reduced pressure
3. additionPotassium carbonate was added (942 mg, 6.81 mmol, 3 equiv.) to the suspension
4. stirringthe reaction was stirred at 70° C. for 18 h
5. temperatureThe reaction mixture was cooled to room temperature
6. customthen quenched with 1 N HCl
7. customThe reaction mixture was partitioned between water (15 mL) and dichloromethane (15 mL)
8. customthe layers were separated
9. extractionThe aqueous layer was extracted with dichloromethane (2×15 mL)
10. concentrationthe combined organic layers were concentrated