反应详情

A mixture of 2,4-dichloro-5-methoxyaniline (1.1 g, 5.7 mmol) and 60% sodium hydride (285 mg, 9.9 mmol) in 30 mL of tetrahydrofuran is heated at reflux for 1 hour. The solution is cooled and 4-chloro-2-iodothieno[2,3-b]pyridine-5-carbonitrile (1.0 g, 3.12 mmol) is added. The reaction mixture is heated at reflux for 5 hours then allowed to stir at room temperature overnight. The resultant dark 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 0.5:9.5 methanol:dichloromethane to provide 0.28 g of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-2-iodothieno[2,3-b]pyridine-5-carbonitrile as an off white solid, mp 231-233° C. An additional 0.09 g is obtained by chromatography of a mixture of unreacted starting material and product using a gradient of 9:1 to 1:1 hexane:ethyl acetate. 1H NMR (DMSO-d6) δ 3.87 (s, 3H), 7.36 (s, 1H), 7.76 (s, 1H), 8.11 (s, 1H), 8.39 (s, 1H), 9.76 (s, 1H); MS 473.8 (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 5 hours
6. customThe resultant dark 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 0.5:9.5 methanol