反应详情

温度

2.5 °C

In a vial, 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile (50, 500 mg, 2.82 mmol) is cooled in an ice water bath, and trifluoromethanesulfonic acid (2.49 mL, 28.15 mmol) is added. The solution is stirred at 0-5° C. for 5 minutes, then 2,6-difluoro-3-nitro-benzoyl chloride (49, 748.5 mg, 3.38 mmol) is added. The reaction is stirred at 0-5° C. for 1 hour, then warmed to room temperature and stirred for 4 days. The reaction is quenched with 5 mL of methanol, and stirred at room temperature for 1 hour. The reaction is poured into saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer is washed with water, brine, dried with magnesium sulfate, filtered and the filtrate is concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with 0-100% ethyl acetate in hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (51, 134 mg).

1. stirringThe reaction is stirred at 0-5° C. for 1 hour
2. temperaturewarmed to room temperature
3. stirringstirred for 4 days
4. customThe reaction is quenched with 5 mL of methanol
5. stirringstirred at room temperature for 1 hour
6. additionThe reaction is poured into saturated aqueous sodium bicarbonate
7. extractionextracted with ethyl acetate
8. washThe organic layer is washed with water, brine
9. dry with materialdried with magnesium sulfate
10. filtrationfiltered
11. concentrationthe filtrate is concentrated under vacuum
12. customThe resulting material is purified by silica gel column chromatography
13. washeluting with 0-100% ethyl acetate in hexane
14. concentrationconcentrated under vacuum