反应详情

(Methoxycarbonylsulfamoyl)triethylammonium hydroxide (internal salt) (90 mg, 3.76 mmol) was added to a solution of 6-[N-(acetylamino)carbamoyl]-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}-4-(2-acetyl-5-methyl-1H-pyrazol-3-ylamino)pyrimidine (Method 51) (500 mg, 0.94 mmol) in anhydrous THF (20 ml) and the reaction heated at reflux for 18 hours. The volatiles were removed by evaporation and the residue was dissolved in methanol (5 ml) and 2N aqueous sodium hydroxide solution (11.0 ml) and stirred at ambient temperature for 15 minutes. The methanol was removed by evaporation and the pH of the resulting solution adjusted to pH 7 with 1N hydrochloric acid. The volatiles were removed evaporation and the residue purified by chromatography on silica gel eluting with DCM/methanol (100:0 increasing in polarity to 90:10). The purified product was then triturated with diethylether and collected by filtration to give the title compound (200 mg, 52%).

1. temperaturethe reaction heated
2. temperatureat reflux for 18 hours
3. customThe volatiles were removed by evaporation
4. dissolutionthe residue was dissolved in methanol (5 ml)
5. customThe methanol was removed by evaporation
6. customThe volatiles were removed
7. customevaporation
8. customthe residue purified by chromatography on silica gel eluting with DCM/methanol (100:0 increasing in polarity to 90:10)
9. customThe purified product was then triturated with diethylether
10. filtrationcollected by filtration