反应详情

Into a suspension of 3-(4-methylphenyl)-2H-1-benzopyran-6-carboxylic acid (150 mg) and 1-hydroxybenzotriazole (114 mg) in acetonitrile (15 ml) was added at room temperature 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (162 mg), and the resulting mixture was stirred for 2 hours. Into the reaction mixture was added a solution of trans-4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]cyclohexylamine dihydrochloride (253 mg), 1,8-diazabicyclo[5,4,0]-7-undecene (257 mg) and triethylamine (0.16 ml) in acetonitrile (20 ml), and the resulting mixture was stirred for 4 hours. After the reaction mixture was concentrated under reduced pressure, water was added to the residue, and the resulting mixture was extracted with chloroform. The organic layer was washed with an aqueous saturated solution of sodium chloride and was dried with magnesium sulfate. After the resulting organic layer was concentrated under reduced pressure to remove the solvent, the residue was subjected to purification using column chromatography (ethanol/ethyl acetate 1:2) and to recrystallization (ethanol) to obtain trans-3-(4-methylphenyl)-N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]cyclohexyl]-2H-1-benzopyran-6-carboxamide (compound 68) (190 mg) as colorless crystals.

1. stirringthe resulting mixture was stirred for 4 hours
2. concentrationAfter the reaction mixture was concentrated under reduced pressure, water
3. additionwas added to the residue
4. extractionthe resulting mixture was extracted with chloroform
5. washThe organic layer was washed with an aqueous saturated solution of sodium chloride
6. dry with materialwas dried with magnesium sulfate
7. concentrationAfter the resulting organic layer was concentrated under reduced pressure
8. customto remove the solvent
9. customthe residue was subjected to purification
10. customto recrystallization (ethanol)