反应详情

In DMF (8 ml) was dissolved 1-methoxycarbonyl-7-(4-morpholinophenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (0.15 g). To the solution was added, under ice-cooling, thionyl chloride (0.07 ml), and the mixture was stirred at room temperature for 30 minutes. Under reduced pressure, the solvent was evaporated, and the residue was suspended in THF (25 ml). The suspension was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.12 g) and triethylamine (0.26 ml) in THF (5 ml), under ice-cooling, and the mixture was stirred under nitrogen atmosphere at room temperature for 4 hours. Under reduced pressure, the solvent was evaporated. To the residue was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with anhydrous magnesium sulfate, and the solvent was evaporated. The residue was purified with silica gel column chromatography (elution solvent: methanol/triethylamine/ethyl acetate) to give crude crystals, which were recrystallized from ethyl acetate/hexane to give 1-methoxycarbonyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-7-(4-morpholinophenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxamide (0.14 g) as colorless crystals.

1. additionTo the solution was added, under ice-
2. temperaturecooling
3. customUnder reduced pressure, the solvent was evaporated
4. additionThe suspension was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.12 g) and triethylamine (0.26 ml) in THF (5 ml), under ice-
5. temperaturecooling
6. customUnder reduced pressure, the solvent was evaporated
7. additionTo the residue was added water
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 (elution solvent: methanol/triethylamine/ethyl acetate)
13. customto give crude crystals, which
14. customwere recrystallized from ethyl acetate/hexane