反应详情

Sodium hydride (0.12 g, 3 mmol, 60% dispersion in mineral oil) was dissolved in N,N-dimethylformamide (1.5 mL), and 4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide (0.47 g, 1.1 mmol) was added thereto, and then, the resulting mixture was stirred at room temperature for 30 minutes. Then, 1,3,2-dioxathiolane-2,2-dioxide (0.14 g, 1.2 mmol) was added thereto, and the resulting mixture was stirred at room temperature. After 1 hour, sodium hydride (40 mg, 1.0 mmol, oily, 60%) was added thereto again, and the resulting mixture was stirred for 30 minutes. Then, 1,3,2-dioxathiolane-2,2-dioxide (12 mg, 0.11 mmol) was added thereto, and the resulting mixture was stirred at room temperature for 1 hour. After the mixture was concentrated under reduced pressure, methanol (5 mL) was added to the residue and insoluble substances were removed by filtration, and the filtrate was concentrated again. To the residue, tetrahydrofuran (2 mL) and 6 M hydrochloric acid (2 mL) were added, and the resulting mixture was stirred at 60° C. for 16 hours. The reaction was cooled to room temperature, and then dissolved in ethyl acetate, and washed with water and saturated saline. The organic layer was dried over anhydrous sodium sulfate and filtered. Then, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate), whereby the objective compound (0.25 g, 48%) was obtained.

1. stirringthe resulting mixture was stirred at room temperature
2. waitAfter 1 hour
3. stirringagain, and the resulting mixture was stirred for 30 minutes
4. stirringthe resulting mixture was stirred at room temperature for 1 hour
5. concentrationAfter the mixture was concentrated under reduced pressure, methanol (5 mL)
6. additionwas added to the residue and insoluble substances
7. customwere removed by filtration
8. concentrationthe filtrate was concentrated again
9. additionTo the residue, tetrahydrofuran (2 mL) and 6 M hydrochloric acid (2 mL) were added
10. stirringthe resulting mixture was stirred at 60° C. for 16 hours
11. temperatureThe reaction was cooled to room temperature
12. dissolutiondissolved in ethyl acetate
13. washwashed with water and saturated saline
14. dry with materialThe organic layer was dried over anhydrous sodium sulfate
15. filtrationfiltered
16. concentrationThen, the filtrate was concentrated under reduced pressure
17. customthe residue was purified by silica gel column chromatography (ethyl acetate), whereby the objective compound (0.25 g, 48%)
18. customwas obtained