反应详情

To 2,4-difluoro-3-(4-pyridin-4-yl-1H-pyrazol-3-yl)-phenylamine (70 mg, 0.25 mmol) (prepared as described in Example 22) in anhydrous N,N-dimethylformamide (2.5 mL) was added trifluoromethyl-phenylisocyanate (35 μL, 0.25 mmol) at 0° C. The reaction was allowed to warm to room temperature and it was stirred under nitrogen atmosphere for two days to yield a mixture of mono- and di-urea derivatives. Solvent was removed under reduced pressure. To the crude of reaction in methanol (3 mL) triethylamine (138 μL, 1 mmol) was added and the reaction was stirred at room temperature for two hours in order to transform the di-urea into the mono-urea derivative. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate and washed successively with NaHCO3 saturated solution. The organic layer was dried over anhydrous sodium sulfate and filtered. The product was isolated by silica gel column chromatography eluting with methanol 10% in methylene chloride.

1. customto yield
2. customSolvent was removed under reduced pressure
3. additionwas added
4. stirringthe reaction was stirred at room temperature for two hours in order
5. customThe solvent was removed under reduced pressure
6. dissolutionthe residue was dissolved in ethyl acetate
7. washwashed successively with NaHCO3 saturated solution
8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
9. filtrationfiltered
10. customThe product was isolated by silica gel column chromatography
11. washeluting with methanol 10% in methylene chloride