反应详情

温度

100 °C

An optically-active compound of 4-(3,3-difluoro-1,6-diaza-spiro[3.5]non-6-yl)-7H-pyrrolo[2,3-d]pyrimidine (6.6 g) was mixed with 1-cyanoacetyl-3,5-dimethylpyrazole (7.7 g), N,N-diisopropylethylamine (4.3 ml) and 1,4-dioxane (132 ml), and the mixture was stirred at 100° C. for 2 hours. The mixture was cooled to room temperature. Then, thereto was added water, and the mixture was extracted with ethyl acetate. The separated aqueous layer was further extracted with ethyl acetate 5 times. The combined organic layer was sequentially washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: chloroform/acetone=3/2 to 2/3). To the resulting residue was added n-heptane, and the mixture was concentrated under reduced pressure. To the resulting residue was added diethylether, and the mixture was slurry-washed and filtered to give a solid (7.5 g). The filtrate was concentrated under reduced pressure. To the resulting residue was added diethylether, and the mixture was slurry-washed to give a solid (0.2 g). The combined solid was purified by silica gel column chromatography (eluent: chloroform/methanol=97/3 to 9/1). To the resulting solid was added ethanol, and the mixture was concentrated under reduced pressure to give the titled compound (7.1 g).

1. temperatureThe mixture was cooled to room temperature
2. extractionthe mixture was extracted with ethyl acetate
3. extractionThe separated aqueous layer was further extracted with ethyl acetate 5 times
4. washThe combined organic layer was sequentially washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe resulting residue was purified by silica gel column chromatography (eluent: chloroform/acetone=3/2 to 2/3)
8. additionTo the resulting residue was added n-heptane
9. concentrationthe mixture was concentrated under reduced pressure
10. additionTo the resulting residue was added diethylether
11. washthe mixture was slurry-washed
12. filtrationfiltered