反应详情

A mixture of 5-(3-chloropropyl)-10,11-dihydro-5H-dibenz[b,f]azepine (1.5 g, 0.0055 mol, prepared similarly as described in example 2) and potassium iodide (5.4 g, 0.0327 mol) in methyl ethyl ketone (100 ml) was heated at reflux temperature for 1 h and then stirred at room temperature overnight. The mixture was filtered and the solvent evaporated in vacuo. The crude halogenide was dissolved in dry dimethyl sulfoxide (15 ml) and kept. A solution of 3-acetylaminobenzoic acid ethyl ester (1.5 g, 7.4 mmol) in dry dimethyl sulfoxide (15 ml) was heated to 50° C. and sodium hydride (0.32 g, 8.1 mmol, 60% oil dispersion) was added in portions. The resulting mixture was heated at 120° C. for 2.5 h, and the mixture was allowed to cool to 80° C. before the above solution containing the halogenide was added. The resulting mixture was heated at 115-120° C. overnight and then allowed to cool to room temperature. Water (100 ml) was added and the resulting mixture was extracted with dichloromethane (3×200 ml). The organic extracts were discarded and pH of the aqueous phase was adjusted to 7. The aqueous phase was extracted with ethyl acetate (100 ml) and dichloromethane (2×100 ml), and the combined organic extracts were dried (MgSO4). The volatiles were removed in vacuo to give a residue which was purified by flash chromatography on silica gel (200 g) using ethyl acetate as eluent, affording 1.0 g of 3-(N-acetyl-N-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propyl)-amino)benzoic acid ethyl ester as an oil.

1. customprepared similarly
2. temperaturewas heated
3. temperatureat reflux temperature for 1 h
4. filtrationThe mixture was filtered
5. customthe solvent evaporated in vacuo
6. dissolutionThe crude halogenide was dissolved in dry dimethyl sulfoxide (15 ml)
7. temperatureThe resulting mixture was heated at 120° C. for 2.5 h
8. temperatureto cool to 80° C. before the above solution
9. additioncontaining the halogenide
10. additionwas added
11. temperatureThe resulting mixture was heated at 115-120° C. overnight
12. temperatureto cool to room temperature
13. extractionthe resulting mixture was extracted with dichloromethane (3×200 ml)
14. extractionThe aqueous phase was extracted with ethyl acetate (100 ml) and dichloromethane (2×100 ml)
15. dry with materialthe combined organic extracts were dried (MgSO4)
16. customThe volatiles were removed in vacuo
17. customto give a residue which
18. customwas purified by flash chromatography on silica gel (200 g)