反应详情

温度

150 °C

A dimethyl sulfoxide (1 ml) solution of tert-butyl [(3S)-3-methylpyrrolidin-3-yl]carbamate (I-345) (300 mg, 1.50 mmol) and triethylamine (244 μl, 1.75 mmol) was added to a dimethyl sulfoxide (6 ml) solution of 4-cyano-7-fluoro-N,N,5-trimethyl-6-phenyl-1,3-benzoxazole-2-carboxamide (I-114) (404 mg, 1.25 mmol) stirred in an oil bath at 150° C., followed by stirring in an oil bath at 150° C. for 30 minutes. The reaction liquid was concentrated under reduced pressure, the residue was dissolved in ethyl acetate, and washed with aqueous 10% citric acid solution, water and saturated brine. After drying over anhydrous sodium sulfate, the insoluble matter was separated by filtration, and the residue obtained by concentration was purified by silica gel column chromatography (eluent, n-hexane:ethyl acetate=1:1→1:2, v/v). The obtained yellow foamy substance was dissolved in dichloromethane (5 ml), and with cooling with ice, trifluoroacetic acid (10 ml) was added, followed by stirring at room temperature for 5 hours. The reaction liquid was concentrated under reduced pressure, then an aqueous saturated sodium hydrogencarbonate solution and water were added, followed by extraction with chloroform. After drying over anhydrous sodium sulfate, the insoluble matter was separated by filtration, the residue obtained by concentration was purified by preparative TLC (eluent, chloroform:methanol=10:1, v/v), and the obtained eluate was purified in slurry with isopropyl ether to obtain the entitled compound (210 mg, 41%) as a pale yellow solid.

1. stirringby stirring in an oil bath at 150° C. for 30 minutes
2. customThe reaction liquid
3. concentrationwas concentrated under reduced pressure
4. dissolutionthe residue was dissolved in ethyl acetate
5. washwashed with aqueous 10% citric acid solution, water and saturated brine
6. dry with materialAfter drying over anhydrous sodium sulfate
7. customthe insoluble matter was separated by filtration
8. customthe residue obtained by concentration
9. customwas purified by silica gel column chromatography (eluent, n-hexane
10. dissolutionThe obtained yellow foamy substance was dissolved in dichloromethane (5 ml)
11. temperaturewith cooling with ice, trifluoroacetic acid (10 ml)
12. additionwas added
13. stirringby stirring at room temperature for 5 hours
14. customThe reaction liquid
15. concentrationwas concentrated under reduced pressure
16. additionan aqueous saturated sodium hydrogencarbonate solution and water were added
17. extractionfollowed by extraction with chloroform
18. dry with materialAfter drying over anhydrous sodium sulfate
19. customthe insoluble matter was separated by filtration
20. customthe residue obtained by concentration
21. customwas purified by preparative TLC (eluent, chloroform
22. custommethanol=10:1, v/v), and the obtained eluate was purified in slurry with isopropyl ether