反应详情

温度

0 °C

Pyridine (1.51 mL, 18.76 mmol) and thionyl chloride (1.03 mL, 14.07 mmol) were added to a solution of 5-chloro-3-(2,4-dimethoxyphenyl)-3-hydroxy-1,3-dihydroindol-2-one (prepared as described in WO 2005/030755, 3.00 g, 9.38 mmol) in dichloromethane (70 mL) while cooling in ice. The reaction mixture was then stirred at 0° C. for 1 hour. While stirring, water was added to the reaction mixture, and it was then extracted with dichloromethane. The organic phase was washed with water and saturated brine, dried over sodium sulfate and concentrated under reduced pressure. 1-Pyridin-4-yl-piperazine (2.17 g, 13.31 mmol) was added to a solution of the 3-chloro-oxindole intermediate obtained in this way in dimethylformamide (25 mL), and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between ethyl acetate and water. The aqueous phase was extracted again with ethyl acetate. The combined organic phase was dried over sodium sulfate and concentrated under reduced pressure, resulting in 1.00 g of the title compound which was employed without further purification in the next step.

1. temperaturewhile cooling in ice
2. stirringWhile stirring
3. extractionwas then extracted with dichloromethane
4. washThe organic phase was washed with water and saturated brine
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated under reduced pressure
7. stirringthe reaction mixture was stirred at room temperature for 12 h
8. concentrationThe reaction mixture was concentrated under reduced pressure
9. customthe residue was partitioned between ethyl acetate and water
10. extractionThe aqueous phase was extracted again with ethyl acetate
11. dry with materialThe combined organic phase was dried over sodium sulfate
12. concentrationconcentrated under reduced pressure