反应详情

温度

75 °C

A solution of Example A5 (0.35 g, 1.260 mmol) in DMF (5 mL) was sparged with argon, treated with TEA (1 mL) trimethylsilylacetylene (0.531 mL, 3.78 mmol), copper(I) iodide (0.024 g, 0.126 mmol) and dichlorobis(triphenylphosphine)palladium(II) [Pd(PPh3)2Cl2](0.088 g, 0.126 mmol) and heated at 75° C. under argon for 16 h. The mixture was cooled to RT, treated with EtOAc, solids removed via filtration through diatomaceous earth, rinsed well with EtOAc and H2O and the layers of the filtrate separated. The aqueous layer was extracted with EtOAc (1×) and the combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness. The resulting material was dissolved in MeOH (20 mL), treated with K2CO3 (300 mg) and stirred at RT for 1 h. The mixture was concentrated to dryness, treated with EtOAc, sonicated, the solids removed via filtration through diatomaceous earth, rinsed well with EtOAc and the filtrate concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex) to afford N-(5-((2-ethynylpyridin-4-yl)oxy)-6-methylpyridin-2-yl)acetamide (102 mg, 30%) as a light red solid. 1H NMR (400 MHz, DMSO-d6): δ 10.62 (s, 1H); 8.40 (d, J=5.8 Hz, 1H); 8.01 (d, J=8.8 Hz, 1H); 7.60 (d, J=6.0 Hz, 1H); 7.04 (d, J=2.5 Hz, 1H); 6.89 (dd, J=5.8, 2.6 Hz, 1H); 4.34 (s, 1H); 2.22 (s, 3H); 2.07 (s, 3H); MS (ESI) m/z: 268.1 (M+H+).

1. temperatureThe mixture was cooled to RT
2. customremoved via filtration through diatomaceous earth
3. washrinsed well with EtOAc and H2O
4. customthe layers of the filtrate separated
5. extractionThe aqueous layer was extracted with EtOAc (1×)
6. washthe combined organics were washed with brine
7. dry with materialdried over Na2SO4
8. concentrationconcentrated to dryness
9. dissolutionThe resulting material was dissolved in MeOH (20 mL)
10. additiontreated with K2CO3 (300 mg)
11. concentrationThe mixture was concentrated to dryness
12. additiontreated with EtOAc
13. customsonicated
14. customthe solids removed via filtration through diatomaceous earth
15. washrinsed well with EtOAc
16. concentrationthe filtrate concentrated to dryness
17. custompurified via silica gel chromatography (EtOAc/Hex)