反应详情

A mixture of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-iodothieno[3,2-b]pyridine-6-carbonitrile (300 mg, 0.63 mmol), 1-dimethylamino-2-propyne (90 μL, 0.84 mmol), 7.5 mg of tetrakis(triphenylphosphine)palladium(0) and 3 mg of copper(I) iodide in 2 mL of triethylamine and 7 mL of benzene is heated at reflux overnight. 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 chloroform. The insoluble material is removed by filtration, washing with chloroform. The filtrate is washed with 10% aqueous hydrochloric acid, water, and saturated aqueous sodium chloride. The combined aqueous layers are brought to pH 8 by adding 2 N sodium hydroxide. The aqueous layer is extracted with chloroform, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with 5% methanol in dichloromethane to provide 225 mg of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-[3-(dimethylamino)prop-1-ynyl]thieno[3,2-b]pyridine-6-carbonitrile as red crystals, mp 164-166° C.; 1H NMR (DMSO-d6) δ 2.21 (s, 6H), 3.53 (s, 2H), 3.85 (s, 3H), 7.37 (s, 1H), 7.62 (s, 1H), 7.78 (s, 1H), 8.62 (s, 1H), 9.77 (s, 1H); MS 429.3, 431.2 (M−H)−.

1. temperatureis heated
2. temperatureat reflux overnight
3. customThe solvents are removed in vacuo
4. additionthe residue is treated with 10 mL of chloroform
5. customThe insoluble material is removed by filtration
6. washwashing with chloroform
7. washThe filtrate is washed with 10% aqueous hydrochloric acid, water, and saturated aqueous sodium chloride
8. additionby adding 2 N sodium hydroxide
9. extractionThe aqueous layer is extracted with chloroform
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 5% methanol in dichloromethane