反应详情

A solution of 4,4,4-trifluoro-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]-pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile (3.1 g, 0.0071 mol) from Step 1 in THF (35 mL, 0.43 mol) and 3.0 M HCl in water (35 mL) was heated to reflux overnight. The solvent was removed by rotary evaporation to give a greenish orange oil/glass. The oil was stirred with ethyl acetate and sat. NaHCO3 (50 mL). The aqueous phase was extracted with ethyl acetate. The organic layers were washed with brine and reduced by rotary evaporation to give an oil/glass residue. The residue was stirred in ethanol (20 mL, 0.3 mol) and 8.0 M ammonium hydroxide in water (10 mL) over a weekend. The solvent was removed by rotary evaporation to give a pale orange foam/solid. The crude was chromatographed with 0-7% MeOH/DCM, 0-0.7% NH4OH to give 3 g of a pale orange paste/solid. The solid was recrystallized from EtOH to give 1.6 g of an off-white crystals (74% yield).

1. temperatureto reflux overnight
2. customThe solvent was removed by rotary evaporation
3. customto give a greenish orange oil/glass
4. extractionThe aqueous phase was extracted with ethyl acetate
5. washThe organic layers were washed with brine
6. customreduced by rotary evaporation
7. customto give an oil/glass residue
8. customThe solvent was removed by rotary evaporation
9. customto give a pale orange foam/solid
10. customThe crude was chromatographed with 0-7% MeOH/DCM, 0-0.7% NH4OH