反应详情

温度

70 °C

To a stirred solution of 4-(5-(4-chlorophenyl)-3-oxo-2,3-dihydropyridazin-4-yl)benzonitrile (10 g, 32.5 mmol) and LiOH.H2O (1.37 g, 32.65 mmol) in MeOH (200 mL) at 70° C. was added bromine (2.6 g, 16.26 mmol). The reaction mixture was stirred at 70° C. for 3 min. After this time, bromine (5.2 g, 32.5 mmol) and LiOH. H2O (2.74 g, 65.3 mmol) were added and the reaction mixture was stirred at 70° C. for an additional 3 min. After this time, another portion of bromine (2.6 g, 16.26 mmol) and LiOH.H2O (1.37 g, 32.65 mmol) was added and the reaction mixture was stirred for 3 min at 70° C. A final portion of bromine (2.6 g, 16.26 mmol) followed by LiOH. H2O (1.37 g, 32.65 mmol) was added and the reaction mixture was stirred at 70° C. for another 3 min. HPLC (Method A) showed disappearance of the starting material. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to give a light yellow solid. This solid was diluted with water (100 mL) and the pH was adjusted to 7 with aq 1.0 N NaOH. The product was extracted with EtOAc (2×100 mL). The combined organic layer was washed with saturated NaCl, dried (MgSO4), filtered and the filtrate was concentrated to obtain 4-(6-bromo-5-(4-chlorophenyl)-3-oxo-2,3-dihydropyridazin-4-yl)benzonitrile as a pale yellow solid (12.1 g, 96%).

1. stirringthe reaction mixture was stirred at 70° C. for an additional 3 min
2. stirringthe reaction mixture was stirred for 3 min at 70° C
3. stirringthe reaction mixture was stirred at 70° C. for another 3 min
4. temperatureThe reaction mixture was cooled to room temperature
5. concentrationconcentrated under reduced pressure
6. customto give a light yellow solid
7. extractionThe product was extracted with EtOAc (2×100 mL)
8. washThe combined organic layer was washed with saturated NaCl
9. dry with materialdried (MgSO4)
10. filtrationfiltered
11. concentrationthe filtrate was concentrated