反应详情

A mixture of 2,4-dichloro-5-methoxyaniline (336 mg, 1.75 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 7-chlorothieno[3,2-b]pyridine-6-carbonitrile (200 mg, 1.02 mmol) is added. The reaction mixture is heated at reflux for 3.5 hours then allowed to stir at room temperature overnight. 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 1:1 ethyl acetate:hexane. The fractions containing product are combined and concentrated. Diethyl ether is added and the insoluble material collected by filtration to provide 131 mg of 7-[(2,4-dichloro-5-methoxyphenyl)amino]thieno[3,2-b]pyridine-6-carbonitrile as a tan solid, mp 216-220° C.; 1H NMR (DMSO-d6) δ 3.85 (s, 3H), 7.40 (3, 1H), 7.46 (d, J=5 Hz, 1H), 7.76 (s, 1H), 8.11 (d, J=5 Hz, 1H), 8.61 (s, 1H), 9.71 (s, 1H); MS 350.2 (M+H)+.

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