反应详情

A mixture of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-iodothieno[3,2-b]pyridine-6-carbonitrile (134 mg, 0.28 mmol), 1-ethynyl-4-methoxybenzene (50 μL, 0.39 mmol), 3 mg of tetrakis(triphenylphosphine)palladium(0) and 5 mg of copper(I) iodide in 2 mL of triethylamine and 7 mL of benzene is heated at reflux for 24 hours. An additional 1 mL of triethylamine and 4 mL of benzene are added and the reaction is heated at reflux for 6 hours. The mixture is cooled to room temperature and 2 mL of methanol are added. The solvents are removed in vacuo and the residue is treated with 10 mL of ethyl acetate. The insoluble material is removed by filtration, washing with ethyl acetate. The filtrate is washed with 10% aqueous hydrochloric acid, water, and saturated aqueous sodium chloride, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with 4:1 hexane:ethyl acetate to provide 92 mg of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-[(4-methoxyphenyl)ethynyl]thieno[3,2-b]pyridine-6-carbonitrile as yellow crystals, mp 249–250° C.; 1H NMR (DMSO-d6) δ 3.81 (s, 3H), 3.86 (s, 3H), 7.01 (d, J=7 Hz, 2H), 7.40 (s, 1H), 7.55 (d, J=7 Hz, 2H), 7.70 (s, 1H), 7.79 (s, 1H), 8.65 (s, 1H), 9.81 (s, 1H); MS 477.9, 479.9 (M−H)−.

1. temperatureis heated
2. temperatureat reflux for 24 hours
3. temperaturethe reaction is heated
4. temperatureat reflux for 6 hours
5. customThe solvents are removed in vacuo
6. additionthe residue is treated with 10 mL of ethyl acetate
7. customThe insoluble material is removed by filtration
8. washwashing with ethyl acetate
9. washThe filtrate is washed with 10% aqueous hydrochloric acid, water, and saturated aqueous sodium chloride
10. dry with materialdried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe residue is purified by flash column chromatography
14. washeluting with 4:1 hexane