反应详情

A mixture of 2,4-dichloro-5-methoxyaniline (0.15 g, 0.73 mmol) and 60% sodium hydride (50 mg, 1.25 mmol) in 15 mL of tetrahydrofuran is heated at reflux for 1 hour. The solution is cooled and 4-chloro-2-methylthieno[2,3-b]pyridine-5-carbonitrile (0.06 g, 0.29 mmol) is added. The reaction mixture is heated at reflux for 3 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 3:7 ethyl acetate:hexane The fractions containing product are combined and concentrated. Diethyl ether is added and the insoluble material collected by filtration to provide 79 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-2-methylthieno[2,3-b]pyridine-5-carbonitrile as a tan solid, mp 179-181° C.; 1H NMR (DMSO-d6) δ 2.57 (s, 3H), 3.85 (s, 3H), 7.32 (s, 1H), 7.39 (s, 1H), 7.74 (s, 1H), 8.35 (s, 1H), 9.61 (s, 1H); MS 362.1 (M−H)−.

1. temperatureis heated
2. temperatureat reflux for 1 hour
3. temperatureThe solution is cooled
4. temperatureThe reaction mixture is heated
5. temperatureat reflux for 3 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 3:7 ethyl acetate
13. additionhexane The fractions containing product
14. concentrationconcentrated
15. additionDiethyl ether is added
16. filtrationthe insoluble material collected by filtration