反应详情

温度

70 °C

To a degassed solution containing (S)-2-amino-5-bromo-N-[methyl(oxo)phenyl-λ6-sulfanylidene]nicotinamide (106 mg, 0.3 mmol) and 3-hydroxyphenylacetylene (50 mg, 0.42 mmol) in 2.0 mL EtOAc at room temperature was added triethylamine (0.13 mL, 0.9 mmol), dichlorobis(triphenylphosphine)palladium(II) (21 mg, 0.03 mmol), and copper(I) iodide (6 mg, 0.03 mmol). The reaction was stirred at 70° C. for 3.3 hours. Additional 3-hydroxyphenylacetylene was added (50 mg, 0.42 mmol) and then again at 5.3 hours (75 mg, 0.63 mmol). The reaction was cooled to room temperature, and after 23 hours additional dichlorobis(triphenylphosphine)palladium(II) (20 mg, 0.03 mmol) was added. The reaction was heated to 60° C. and 3-hydroxyphenylacetylene (120 mg, 1.0 mmol) in 0.7 mL EtOAc (degassed) added dropwise over 7 minutes. The heat was removed after 1 hour and the reaction stirred an additional 22 hours at room temperature. The reaction was dissolved in EtOAc and washed with H2O. The EtOAc layer was extracted with 2% aqueous HCl. The combined acidic aqueous layers were washed with 30% EtOAc/hexane and then made basic with Na2CO3. The basic aqueous layer was extracted with EtOAc. Then the combined organic layers washed with brine, dried with anhydrous Na2SO4 and concentrated. The yellow oil was purified by chromatography (silica gel, CHCl3/EtOAc) to give the title compound as a white solid (5 mg, 4%).

1. waitagain at 5.3 hours (75 mg, 0.63 mmol)
2. temperatureThe reaction was cooled to room temperature
3. temperatureThe reaction was heated to 60° C.
4. customThe heat was removed after 1 hour
5. stirringthe reaction stirred an additional 22 hours at room temperature
6. dissolutionThe reaction was dissolved in EtOAc
7. washwashed with H2O
8. extractionThe EtOAc layer was extracted with 2% aqueous HCl
9. washThe combined acidic aqueous layers were washed with 30% EtOAc/hexane
10. extractionThe basic aqueous layer was extracted with EtOAc
11. washThen the combined organic layers washed with brine
12. dry with materialdried with anhydrous Na2SO4
13. concentrationconcentrated
14. customThe yellow oil was purified by chromatography (silica gel, CHCl3/EtOAc)