反应详情

温度

100 °C

di-tert-Butyl {(4aS,5R,7aS)-7a-[2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl}imidodicarbonate (0.13 g, 0.22 mmol) was dissolved in 1,2-dimethoxyethane (1.5 mL), water (0.7 mL) and ethanol (0.5 mL) The resulting solution was heated to 100° C. and to it was added 3-bromo-5-(cyclopropyloxy)pyridine (0.28 g, 1.32 mmol), cesium carbonate (0.43 g, 1.32 mmol) and bis(triphenylphosphine)palladium (II) dichloride (0.046 g, 0.066 mmol) and the reaction was stirred at 100° C. After 1 hour, the reaction mixture was cooled to room temperature, diluted with saturated aqueous NaHCO3 and extracted with EtOAc (×3). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified using column chromatography gradient 0-60% EtOAc in hexane). The purified product was dissolved in DCM (2 mL) and trifluoroacetic acid (1 mL). After 1 hour, the solvents were removed in vacuo. The residue was basified with saturated aqueous NaHCO3 and extracted with DCM (×3). The combined organic layers were dried (MgSO4), filtered and concentrated to leave the title compound. (58 mg)

1. temperaturethe reaction mixture was cooled to room temperature
2. extractionextracted with EtOAc (×3)
3. dry with materialThe combined organic layers were dried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was purified
7. dissolutionThe purified product was dissolved in DCM (2 mL)
8. waitAfter 1 hour
9. customthe solvents were removed in vacuo
10. extractionextracted with DCM (×3)
11. dry with materialThe combined organic layers were dried (MgSO4)
12. filtrationfiltered
13. concentrationconcentrated