反应详情

7-[(3S)-3-(Dimethylamino)pyrrolidin-1-yl]-5-methyl-2-(methylamino)-6-phenyl-1,3-benzoxazole-4-carbonitrile (#53) (60 mg, 0.16 mmol) was dissolved in tetrahydrofuran (1.2 ml), and with cooling with ice, acetyl chloride (14 μl, 0.19 mmol) and diisopropylethylamine (38 μl, 0.22 mmol) were added, followed by stirring at room temperature for 2 hours. Further, acetyl chloride (14 μl, 0.19 mmol) was added, followed by heating under reflux for 1.5 hours. Since the reaction did not go on, pyridine (1.2 ml) was added, followed by stirring at 90° C. for 15 hours. After cooling followed by fractionation with water and ethyl acetate, the organic layer was washed with saturated brine. The obtained organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated away under reduced pressure. The resulting residue was subjected to preparative silica gel column chromatography. Elution with a mixed solvent of chloroform/methanol (10:1, v/v) gave the entitled compound (11 g, 0.03 mmol, 17%) as a brown oily substance.

1. additionwere added
2. temperatureby heating
3. temperatureunder reflux for 1.5 hours
4. additionwas added
5. stirringby stirring at 90° C. for 15 hours
6. temperatureAfter cooling
7. washthe organic layer was washed with saturated brine
8. dry with materialThe obtained organic layer was dried over anhydrous sodium sulfate
9. customthe solvent was evaporated away under reduced pressure
10. washElution with a mixed solvent of chloroform/methanol (10:1