反应详情

With cooling with ice, 1-hydroxybenzotriazole (134 mg, 0.991 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (174 mg, 0.908 mmol) and triethylamine (127 μl, 0.980 mmol) were added to an acetonitrile (8 ml) solution of 4-amino-6-fluoro-5-hydroxy-2-methylbiphenyl-3-carbonitrile (I-41) (200 mg, 0.826 mmol) and 2-furylacetic acid (115 mg, 0.908 mmol), followed by stirring at room temperature for 16 hours. The reaction liquid was concentrated under reduced pressure, the residue was dissolved in ethyl acetate, and washed with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate, then concentrated under reduced pressure, and the resulting residue was dissolved in xylene (20 ml), then pyridinium p-toluenesulfonate (50 mg) was added, followed by heating under reflux in an oil bath at 160° C. for 1 hour. The reaction liquid was concentrated under reduced pressure, then the residue was dissolved in ethyl acetate, washed with saturated brine. After drying over anhydrous sodium sulfate, the insoluble matter was separated by filtration, and the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography (eluent, n-hexane:ethyl acetate=4:1, v/v) to obtain the entitled compound (155 mg, 57%) as a pale yellow solid.

1. customThe reaction liquid
2. concentrationwas concentrated under reduced pressure
3. dissolutionthe residue was dissolved in ethyl acetate
4. washwashed with water and saturated brine
5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
6. concentrationconcentrated under reduced pressure
7. dissolutionthe resulting residue was dissolved in xylene (20 ml)
8. additionpyridinium p-toluenesulfonate (50 mg) was added
9. temperatureby heating
10. temperatureunder reflux in an oil bath at 160° C. for 1 hour
11. customThe reaction liquid
12. concentrationwas concentrated under reduced pressure
13. dissolutionthe residue was dissolved in ethyl acetate
14. washwashed with saturated brine
15. dry with materialAfter drying over anhydrous sodium sulfate
16. customthe insoluble matter was separated by filtration
17. customthe residue obtained by concentration under reduced pressure
18. customwas purified by silica gel column chromatography (eluent, n-hexane