反应详情

A solution of the compound (500 mg, 0.98 mmol) obtained in Example 52-1), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (210 mg, 1.08 mmol), tetrakis(triphenylphosphine)palladium(0) (114 mg, 0.10 mmol), and potassium carbonate (272 mg, 1.97 mmol) in 1,2-dimethoxyethane (6 mL) and water (3 mL) was stirred at 120° C. for 1 h under microwave irradiation. The reaction mixture was cooled to room temperature, water (10 mL) was added to the reaction mixture, the mixture was extracted with ethyl acetate, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After concentration under reduced pressure, the residue was partially purified by silica gel chromatography (ethyl acetate:methanol=40:60). A solution of the residue and 4 M hydrochloric acid (1,4-dioxane solution, 3 mL) in methanol (6 mL) was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure, a 5 N aqueous sodium hydroxide solution (10 mL) was added to the residue, the mixture was extracted with dichloromethane, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After concentration under reduced pressure, the residue was partially purified by silica gel chromatography (ethyl acetate/methanol=40:60). The residue was dissolved in a solution (8 mL) of ethyl acetate/methanol=3:1, and diisopropyl ether (20 mL) was gradually added to the mixture with stirring at room temperature to prepare a suspension. The suspension was stirred at 60° C. for 1 h and stirred for 1 h with cooling to room temperature. The colorless precipitate was collected by filtration and washed with diisopropyl ether. The solid was dried under reduced pressure to obtain the title compound (46 mg, 12%) as a colorless solid.

1. extractionthe mixture was extracted with ethyl acetate
2. washthe organic layer was washed with saturated sodium chloride solution
3. dry with materialdried with anhydrous sodium sulfate
4. concentrationAfter concentration under reduced pressure
5. customthe residue was partially purified by silica gel chromatography (ethyl acetate:methanol=40:60)
6. concentrationThe reaction mixture was concentrated under reduced pressure
7. additiona 5 N aqueous sodium hydroxide solution (10 mL) was added to the residue
8. extractionthe mixture was extracted with dichloromethane
9. washthe organic layer was washed with saturated sodium chloride solution
10. dry with materialdried with anhydrous sodium sulfate
11. concentrationAfter concentration under reduced pressure
12. customthe residue was partially purified by silica gel chromatography (ethyl acetate/methanol=40:60)
13. dissolutionThe residue was dissolved in a solution (8 mL) of ethyl acetate/methanol=3:1, and diisopropyl ether (20 mL)
14. additionwas gradually added to the mixture
15. stirringwith stirring at room temperature
16. customto prepare a suspension
17. stirringThe suspension was stirred at 60° C. for 1 h
18. stirringstirred for 1 h
19. temperaturewith cooling to room temperature
20. filtrationThe colorless precipitate was collected by filtration
21. washwashed with diisopropyl ether
22. customThe solid was dried under reduced pressure