反应详情

温度

100 °C

In a 35-mL resealable vessel, cesium carbonate (0.621 g, 1.905 mmol), 1-iodo-2,2-dimethylpropane (0.211 mL, 1.587 mmol), and crude (S,E)-N′-(7-(2-fluoropyridin-3-yl)-3-hydroxy-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazin]-2′-yl)-N,N-dimethylformimidamide (0.344 g, 0.794 mmol) were taken up in DMF (8 mL). The vessel was sealed and heated in a 100° C. oil bath. After 6 h, the reaction was concentrated. The residue was taken up in 10% MeOH/DCM (120 mL) and the organic layer was extracted with water (2×10 mL). The organic layer was dried over MgSO4, filtered and concentrated. The residue was taken up in dioxane (8 mL), and a dioxane solution of HCl (4 M, 2 mL) was added. The vessel was sealed and heated in a 60° C. oil bath. After 1 h, the reaction was concentrated. The residue was diluted with water (30 mL) and the aqueous phase was extracted with 10% MeOH/DCM (3×50 mL). The organics were dried over magnesium sulfate, filtered, and concentrated. The material was purified by chromatography using 65:35:0.5:1 EtOAc-hexane-MeOH-Et3N to afford (S)-7-(2-fluoropyridin-3-yl)-3-(neopentyloxy)-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazin]-2′-amine (4.5 mg, 0.010 mmol). MS (m/z) 449 (M+H)+.

1. customThe vessel was sealed
2. concentrationthe reaction was concentrated
3. extractionthe organic layer was extracted with water (2×10 mL)
4. dry with materialThe organic layer was dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. additiona dioxane solution of HCl (4 M, 2 mL) was added
8. customThe vessel was sealed
9. temperatureheated in a 60° C. oil bath
10. waitAfter 1 h
11. concentrationthe reaction was concentrated
12. additionThe residue was diluted with water (30 mL)
13. extractionthe aqueous phase was extracted with 10% MeOH/DCM (3×50 mL)
14. dry with materialThe organics were dried over magnesium sulfate
15. filtrationfiltered
16. concentrationconcentrated
17. customThe material was purified by chromatography