反应详情

A vial was charged with (S)-2-amino-4′-fluoro-7′-(pyrimidin-5-yl)-5H-spiro[oxazole-4,9′-xanthen]-2′-ol (61.0 mg, 0.167 mmol), cesium carbonate (82 mg, 0.251 mmol), and DMF (670 μL). The resulting mixture was stirred vigorously for 10 min, then the vial was placed in large ice-bath for 10 min. 2-fluoro-2-methylpropyl trifluoromethanesulfonate (33.3 μL, 0.201 mmol) was added dropwise and the ice-bath was removed after 5 minutes. The mixture was stirred at for 6 hours, then the mixture was diluted with water (10 mL) and extracted with EtOAc (3×5 mL). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The residue was chromatographed on a 12 g Redi-Sep column, eluting with 5-60% gradient of DCM/MeOH/NH4OH (90:10:1) in DCM to give (S)-4′-fluoro-2′-(2-fluoro-2-methylpropoxy)-7′-(pyrimidin-5-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine as an off-white solid. Found MS: MH+=439.

1. customfor 10 min
2. customthe ice-bath was removed after 5 minutes
3. stirringThe mixture was stirred at for 6 hours
4. additionthe mixture was diluted with water (10 mL)
5. extractionextracted with EtOAc (3×5 mL)
6. dry with materialThe combined organic extracts were dried over sodium sulfate
7. filtrationfiltered
8. customevaporated
9. customThe residue was chromatographed on a 12 g Redi-Sep column
10. washeluting with 5-60% gradient of DCM/MeOH/NH4OH (90:10:1) in DCM