反应详情

温度

80 °C

3-ethynyl-4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine (30.0 mg, 0.119 mmol), 4-iodo-5-methyl-1-phenyl-1H-pyrazole (67.6 mg, 0.238 mmol), and bis(triphenylphosphine)palladium(II) chloride (8.4 mg, 0.012 mmol) were combined into one vial fitted with a Teflon septum. The vial was flushed with nitrogen and tetra-n-butylammonium fluoride (0.36 mL, 0.36 mmol, 1M in THF) and tetrahydrofuran (0.2 mL) were added. After sparging with nitrogen for 5 minutes, the reaction was heated to 80° C. for one hour. The reaction was cooled to ambient temperature, then diluted with ethyl acetate, and washed with saturated aqueous sodium bicarbonate. The organic layer was separated, and the aqueous layer was back extracted with ethyl acetate two times. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by preparative HPLC reverse phase (C-18), eluting with acetonitrile/water+0.05% TFA. The fractions containing product were combined and diluted in ethyl acetate, then washed with aqueous sodium bicarbonate and dried over sodium sulfate. The solution was filtered and concentrated under reduced pressure to give 4-methoxy-3-[(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethynyl]-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine

1. additionwere added
2. customAfter sparging with nitrogen for 5 minutes
3. temperatureThe reaction was cooled to ambient temperature
4. additiondiluted with ethyl acetate
5. washwashed with saturated aqueous sodium bicarbonate
6. customThe organic layer was separated
7. extractionthe aqueous layer was back extracted with ethyl acetate two times
8. dry with materialThe combined organic layers were dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customThe residue was purified by preparative HPLC reverse phase (C-18)
12. washeluting with acetonitrile/water+0.05% TFA
13. additionThe fractions containing product
14. additiondiluted in ethyl acetate
15. washwashed with aqueous sodium bicarbonate
16. dry with materialdried over sodium sulfate
17. filtrationThe solution was filtered
18. concentrationconcentrated under reduced pressure