反应详情

6-(3-Chlorophenyl)-4-cyano-7-fluoro-N,N,5-trimethyl-1,3-benzoxazole-2-carboxamide (I-311) (500 mg, 1.40 mmol) was dissolved in dimethyl sulfoxide (20 ml), and at room temperature, triethylamine (215 μl, 1.54 mmol) was added. The solution was gradually heated from room temperature up to 150° C., and a solution of (3S)-3-(methylamino)pyrrolidine (164 μl, 1.54 mmol) dissolved in dimethyl sulfoxide (3 ml) was added all at a time. After stirred at the same temperature for 30 minutes, this was cooled to room temperature. The solvent was evaporated away under reduced pressure, and the resulting residue was fractionated with chloroform and an aqueous saturated sodium hydrogencarbonate solution. The aqueous layer was further extracted twice with chloroform. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the solvent was evaporated away, and the resulting residue was first roughly purified by middle-pressure liquid chromatography using an eluent of chloroform:methanol=95:5 (v/v), and then the roughly-purified product was purified by preparative TLC (eluent, chloroform:7 N ammonia/methanol solution=95:5, v/v), and further the obtained solid was purified in slurry with diisopropyl ether to obtain the entitled compound (250 mg, 41%) as a pale yellow solid.

1. temperatureThe solution was gradually heated from room temperature up to 150° C.
2. additionwas added all at a time
3. customThe solvent was evaporated away under reduced pressure
4. extractionThe aqueous layer was further extracted twice with chloroform
5. washwashed with saturated brine
6. dry with materialdried over anhydrous sodium sulfate
7. customThe insoluble matter was separated by filtration
8. customthe solvent was evaporated away
9. customthe resulting residue was first roughly purified by middle-pressure liquid chromatography
10. custommethanol=95:5 (v/v), and then the roughly-purified product was purified by preparative TLC (eluent, chloroform
11. custom7 N ammonia/methanol solution=95:5, v/v), and further the obtained solid was purified in slurry with diisopropyl ether