反应详情

温度

100 °C

To a sealed vessel was charge with (2-fluoropyridin-3-yl)boronic acid (1.543 g, 10.95 mmol), 7′-bromo-4′-fluoro-2′-methoxy-5-(methoxymethyl)-5H-spiro[thiazole-4,9′-xanthen]-2-amine (1.34 g, 3.04 mmol, prepared as in Method CC25), potassium carbonate (1.5M in water) (6.08 mL, 9.12 mmol) in dioxane (15 mL). It was purged with N2 and finally AmPHOS (0.13 g, 0.18 mmol) was added. The mixture was heated in oil bath at 100° C. for 20 min. The reaction mixture was allowed to cool to rt. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give the crude material as an orange oil. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a gold Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 30% to 50% to 75% DCM/MeOH/NH4OH in 40% EtOAc in heptane, to provide (4S,5S)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-methoxy-5-(methoxymethyl)-5H-spiro[thiazole-4,9′-xanthen]-2-amine (817 mg, 1.80 mmol, 59% yield) as light brown foam.

1. additionwas added
2. temperatureto cool to rt
3. extractionextracted with EtOAc
4. washThe organic layer was washed with brine
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customto give the crude material as an orange oil
9. customThe crude material was absorbed onto a plug of silica gel
10. custompurified by chromatography through a gold Redi-Sep pre-packed silica gel column (40 g)
11. washeluting with a gradient of 30% to 50% to 75% DCM/MeOH/NH4OH in 40% EtOAc in heptane