反应详情

温度

130 °C

In a round bottom flask equipped with reflux condenser, a mixture of N-(4-bromo-2-fluorophenyl)-2-{[1-(cyclopropylcarbonyl)-3-azetidinyl]acetyl}hydrazinecarboxamide (4.77 mmol) and potassium carbonate (23.84 mmol) in 1-propanol (10 mL) and water (100 mL) was stirred at vigorous reflux (oil bath, 130° C.) for 22 h. The pale yellow solution was cooled to room temperature and concentrated in vacuo. Water (12 mL) was added to the flask followed by 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline (5.24 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.24 mmol) and 1,4-dioxane (30 mL). The flask containing the reaction mixture was equipped with stir bar and reflux condenser, and the reaction was stirred at 100° C. for 5 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (100 mL) and water (50 mL), and the layers were separated. The aqueous layer was adjusted to pH˜5 using 1N HCl solution and extracted with ethyl acetate (2×100 mL). The organic layers were combined, dried over magnesium sulphate, and concentrated in vacuo. The aqueous layer was lyophilized to give a solid, which was taken up into methanol (25 mL), dichloromethane (25 mL) and ethyl acetate (25 mL) and filtered to remove the salts. The mother liquor was concentrated in vacuo. Methanol (5 mL) was added and a precipitate formed. The precipitate was filtered off and the mother liquor was concentrated in vacuo to provide the title compound as an oil (815 mg, 67% pure, 31% yield). MS(ES)+ m/e 376.0 [M+H]+.

1. customIn a round bottom flask equipped
2. temperaturewith reflux condenser
3. temperatureThe pale yellow solution was cooled to room temperature
4. concentrationconcentrated in vacuo
5. additionWater (12 mL) was added to the flask
6. additionThe flask containing the reaction mixture
7. customwas equipped
8. stirringwith stir bar
9. temperaturereflux condenser
10. stirringthe reaction was stirred at 100° C. for 5 h
11. temperatureThe reaction mixture was cooled to room temperature
12. customthe layers were separated
13. extractionextracted with ethyl acetate (2×100 mL)
14. dry with materialdried over magnesium sulphate
15. concentrationconcentrated in vacuo
16. customto give a solid, which
17. filtrationfiltered
18. customto remove the salts
19. concentrationThe mother liquor was concentrated in vacuo
20. additionMethanol (5 mL) was added
21. customa precipitate formed
22. filtrationThe precipitate was filtered off
23. concentrationthe mother liquor was concentrated in vacuo