反应详情

温度

90 °C

(5S)-3-Bromo-7-(3-pyridinyl)spiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazol]-2′-amine (170 mg, 0.415 mmol), diisopropyl amine (2911 μL, 20.77 mmol), copper iodide (15.82 mg, 0.083 mmol), tetrakis(triphenylphosphine)palladium (48.0 mg, 0.042 mmol) and DMF (2769 μL, 0.415 mmol) were combined in a sealable tube, which was then flushed with argon and heated at 90° C. for 5 hours. After cooling to room temperature the reaction in the tube was diluted with water (25 mL) and poured into a separatory funnel containing ethyl acetate (25 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (4×50 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to provide a brown oil that was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-10% methanol in methylenechloride with 0.1% ammonium hydroxide) to provide (5S)-3-(3,3-dimethyl-1-butyn-1-yl)-7-(3-pyridinyl)spiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazol]-2′-amine (110 mg, 0.268 mmol, 64.5% yield) as a brown foam. MS m/z=411.2 [M+H]+. Calc'd for C25H23N4O3: 411.2.

1. customwhich was then flushed with argon
2. temperatureAfter cooling to room temperature
3. customthe reaction in the tube
4. additionpoured into a separatory funnel
5. customThe layers were separated
6. extractionthe aqueous layer was extracted with ethyl acetate (4×50 mL)
7. washThe combined organic layers were washed with brine
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto provide a brown oil that
12. customwas purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-10% methanol in methylenechloride with 0.1% ammonium hydroxide)