反应详情

In DMF (6 ml) was dissolved 1-butyl-7-[4-(2-propoxyethoxy)phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (0.30 g). Under ice-cooling, to the mixture was added thionyl chloride (0.15 ml). The mixture was stirred at room temperature for 30 minutes. The solvent was evaporated under reduced pressure. In THF (20 ml) was suspended the residue, and the suspension was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.17 g) and triethylamine (0.42 ml) in THF (5 ml), under ice-cooling. The mixture was stirred at room temperature overnight under nitrogen atmosphere. The solvent was evaporated under reduced solvent. Water was added to the mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified with silica gel column chromatography (ethyl acetate/methanol/triethylamine). The material was dissolved in ethyl acetate-ethanol, and 6N hydrochloric acid was added to the solution. The solvent was evaporated. Diethyl ether was added to the residue, and the precipitates were filtered to give 1-butyl-7-[4-(2-propoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide dihydrochloride (Compound 30) (0.36 g) as pale yellow amorphous.

1. temperatureUnder ice-cooling, to the mixture
2. customThe solvent was evaporated under reduced pressure
3. additionthe suspension was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.17 g) and triethylamine (0.42 ml) in THF (5 ml), under ice-
4. temperaturecooling
5. stirringThe mixture was stirred at room temperature overnight under nitrogen atmosphere
6. customThe solvent was evaporated under reduced solvent
7. additionWater was added to the mixture
8. extractionthe mixture was extracted with ethyl acetate
9. washThe organic layer was washed with water and saturated brine
10. dry with materialdried with anhydrous magnesium sulfate
11. customThe solvent was evaporated
12. customthe residue was purified with silica gel column chromatography (ethyl acetate/methanol/triethylamine)
13. dissolutionThe material was dissolved in ethyl acetate-ethanol
14. addition6N hydrochloric acid was added to the solution
15. customThe solvent was evaporated
16. additionDiethyl ether was added to the residue
17. filtrationthe precipitates were filtered