反应详情

A mixture of 2,4-dichloro-5-methoxyaniline (300 mg, 1.57 mmol) and 60% sodium hydride (70 mg, 1.75 mmol) in 10 mL of tetrahydrofuran is heated at reflux for 30 minutes The solution is cooled and 4-chlorothieno[2,3-b]pyridine-5-carbonitrile (150 mg, 0.8 mmol) [Khan, M. A.; Guarconi, A. E., J. Heterocyclic Chem., 14, 807 (1977)] is added. The reaction mixture is heated at reflux for 3.5 hours. The resultant black solution is partitioned between ethyl acetate and water. The organic layer is washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with 2:3 ethyl acetate:hexane. The fractions containing product are combined and concentrated. Diethyl ether is added and the insoluble material is collected by filtration to provide 60 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]thieno[2,3-b]pyridine-5-carbonitrile as a tan solid, mp 197–199° C.; 1H NMR (DMSO-d6) δ 3.85 (s, 3H), 7.38 (s, 1H), 7.68 (d, J=5.7 Hz, 1H), 7.76 (s, 1H), 7.81 (d, J=5.7 Hz, 1H), 8.43 (s, 1H), 9.80 (s, 1); MS 348.2 (M−H)−.

1. temperatureis heated
2. temperatureat reflux for 30 minutes The solution
3. temperatureis cooled
4. addition, 14, 807 (1977)] is added
5. temperatureThe reaction mixture is heated
6. temperatureat reflux for 3.5 hours
7. customThe resultant black solution is partitioned between ethyl acetate and water
8. washThe organic layer is washed with water
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe residue is purified by flash column chromatography
13. washeluting with 2:3 ethyl acetate
14. additionThe fractions containing product
15. concentrationconcentrated
16. additionDiethyl ether is added
17. filtrationthe insoluble material is collected by filtration