反应详情

A 25-mL flask was charged with (S)-2′-amino-3-bromo-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-7-ol (1.012 g, 2.91 mmol), copper(i) iodide (0.055 g, 0.291 mmol), and tetrakis(triphenylphosphine)palladium (0.034 g, 0.029 mmol). The vial was flushed with Ar(g), then a septum was attached. DMF (5.81 mL), diisopropylamine (6.11 mL, 43.6 mmol), and 2-methylbut-3-yn-2-ol (1.137 mL, 11.63 mmol) were added in sequence to give a clear, brown solution. A reflux condenser was attached, and the flask was placed in a 75° C. oil bath for 4 hours. The mixture was diluted with water (35 mL) and extracted with DCM (4×20 mL). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The residue, which contained a considerable amount of DMF, was loaded onto a 10-g SCX-2 column with the aid of methanol. The column was eluted with methanol to remove impurities, then with 2M ammonia in methanol to elute the product. The filtrate was evaporated, and the residue was chromatographed on an 80-g Redi-Sep column, eluting with 0-10% MeOH/DCM to give (S)-2′-amino-3-(3-hydroxy-3-methylbut-1-ynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-7-ol.

1. customThe vial was flushed with Ar(g)
2. customto give a clear, brown solution
3. customA reflux condenser was attached
4. customwas placed in a 75° C.
5. customfor 4 hours
6. extractionextracted with DCM (4×20 mL)
7. dry with materialThe combined organic extracts were dried over sodium sulfate
8. filtrationfiltered
9. customevaporated
10. washThe column was eluted with methanol
11. customto remove impurities
12. washwith 2M ammonia in methanol to elute the product
13. customThe filtrate was evaporated
14. customthe residue was chromatographed on an 80-g Redi-Sep column
15. washeluting with 0-10% MeOH/DCM