反应详情

温度

40 °C

To NaH (60 wt. % dispersion in oil; 0.09 g, 2.25 mmol) suspended in THF (4 mL) was added (2,5-difluoro-3-{[(methyloxy)methyl]oxy}phenyl)acetonitrile (0.240 g, 1.13 mmol) and then 1-acetylimidazole (0.186 g, 1.69 mmol). The mixture was stirred at 40° C. for 0.3 h. The mixture was cooled to room temperature, was acidified with 1 N HCl and ethyl acetate. The organic portion was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a yellow oil which was dissolved in dichloromethane:MeOH (1:1, 8 mL) and treated with para-toluenesulfonic acid monohydrate (0.045 g, 0.237 mmol) at 40° C. for 15 h. The mixture was partitioned between ethyl acetate and saturated sodium bicarbonate solution. The aqueous portion was extracted with ethyl acetate. The combined organic portion was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a yellow oil which was dissolved in EtOH (4 mL) and treated with tert-butylhydrazine hydrochloride (0.136 g, 1.09 mmol) at 75° C. for 18 h and at room temperature for 38 h. The mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution. The aqueous portion was extracted with ethyl acetate. The combined organic portion was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford 3-[5-amino-1-(1,1-dimethylethyl)-3-methyl-1H-pyrazol-4-yl]-2,5-difluorophenol as a pale brown solid (0.248 g, 0.883 mmol, 78% yield). MS (EI) for C14H17F2N3O: 282 (MH+).

1. temperatureThe mixture was cooled to room temperature
2. washThe organic portion was washed with brine
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customto afford a yellow oil which
7. customThe mixture was partitioned between ethyl acetate and saturated sodium bicarbonate solution
8. extractionThe aqueous portion was extracted with ethyl acetate
9. washThe combined organic portion was washed with brine
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customto afford a yellow oil which
14. concentrationThe mixture was concentrated in vacuo
15. customthe residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution
16. extractionThe aqueous portion was extracted with ethyl acetate
17. washThe combined organic portion was washed with brine
18. dry with materialdried over sodium sulfate
19. filtrationfiltered
20. concentrationconcentrated in vacuo