反应详情

温度

80 °C

To a solution of (S)-4-(4-(1,6-dihydro-1-methyl-6-oxo-4-(pyrimidin-4-yl)pyrimidin-2-yl)-[1,4]oxazepan-6-yl)benzonitrile (183 mg, 0.471 mmol) in ethanol (0.95 ml) was added 50 wt. %—hydroxylamine aqueous solution (96.4 mg, 1.46 mmol) at room temperature. The mixture was stirred at 80° C. for 2 hours and concentrated. The residue was partitioned between water and ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. N,N-dimethylformamide (0.95 ml), triethylamine (143 mg, 1.41 mmol) and acetic anhydride (62.5 mg, 0.612 mmol) was added to the residue at 0° C. The mixture was stirred at room temperature. After 2 hours, the mixture was heated to 135° C. and stirred for 2 hours. The resulting mixture cooled to room temperature was partitioned between water and chloroform. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluent: chloroform/methanol=97/3) to afford (S)-3-methyl-2-(6-(4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl)-[1,4]oxazepan-4-yl)-6-(pyrimidin-4-yl)pyrimidin-4(3H)-one (A085) as white solid (126 mg, 60%).

1. concentrationconcentrated
2. customThe residue was partitioned between water and ethyl acetate
3. dry with materialThe organic layer was dried over sodium sulfate
4. concentrationconcentrated in vacuo
5. stirringThe mixture was stirred at room temperature
6. waitAfter 2 hours
7. temperaturethe mixture was heated to 135° C.
8. stirringstirred for 2 hours
9. temperatureThe resulting mixture cooled to room temperature
10. customwas partitioned between water and chloroform
11. washThe organic layer was washed with brine
12. dry with materialdried over sodium sulfate
13. concentrationconcentrated in vacuo
14. customThe residue was purified by silica gel column chromatography (eluent: chloroform/methanol=97/3)