反应详情

温度

80 °C

A solution of 8-bromo-N-isopropyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (200 mg, 0.5 mmol) in toluene (5 mL, 0.05 mol) under nitrogen atmosphere was treated with phosphorus pentachloride (0.182 g, 0.87 mmol) in one portion. The flask was sealed and heated at 80° C. for 2 h, cooled to room temperature and the solvent concentrated under reduced pressure with care to avoid atmospheric exposure. The crude residue was taken up in methylene chloride (8 mL, 0.1 mol) and treated with methyl hydrazinecarboxylate (0.123 g, 1.36 mmol). The resulting suspension was stirred at room temperature for 2 h. The reaction mixture was diluted with saturated sodium bicarbonate and extracted with methylene chloride. The combined organics were washed with brine, dried over sodium sulfate and concentrated. The crude residue was dissolved in ethanol (5 mL) and potassium carbonate (0.2264 g, 1.64 mmol) was added. The reaction mixture was stirred at 80° C. for 2 h. 0.5 mL water was added and the heating continued overnight. The mixture was concentrated, diluted with water and extracted with ethyl acetate. The organics were washed with brine, concentrated, and the resultant residue purified by flash column chromatography to give 265 (75 mg). 1H NMR (dmso-d6, 500 MHz) δ 11.9 (s, 1H), 7.60 (m, 1H), 7.30-7.23 (m, 3H), 4.44 (pentet, 1H), 4.32 (t, 2H), 3.22 (t, 2H), 1.46 (d, 6H). MS (ESI) 408.1

1. customThe flask was sealed
2. temperaturecooled to room temperature
3. concentrationthe solvent concentrated under reduced pressure with care
4. extractionextracted with methylene chloride
5. washThe combined organics were washed with brine
6. dry with materialdried over sodium sulfate
7. concentrationconcentrated
8. dissolutionThe crude residue was dissolved in ethanol (5 mL)
9. stirringThe reaction mixture was stirred at 80° C. for 2 h
10. waitthe heating continued overnight
11. concentrationThe mixture was concentrated
12. additiondiluted with water
13. extractionextracted with ethyl acetate
14. washThe organics were washed with brine
15. concentrationconcentrated
16. customthe resultant residue purified by flash column chromatography