反应详情

Into a suspension of 2-(4-methylphenyl)-6,7-dihydro-5H-benzocycloheptene-8-carboxylic acid (200 mg) and 1-hydroxybenzotriazole (146 mg) in acetonitrile (10 ml) was added at room temperature 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (207 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 (323 mg), 1,8-diazabicyclo[5,4,0]-7-undecene (326 mg) and triethylamine (0.2 ml) in acetonitrile (15 ml), and the resulting mixture was stirred for 10 hours. After the reaction mixture was concentrated under reduced pressure, water was added to the residue, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with an aqueous saturated solution of sodium chloride and was dried with anhydrous magnesium sulfate. The resulting organic layer was evaporated under reduced pressure to remove the solvent and the residue was then subjected to purification using column chromatography (ethanol/ethyl acetate 1:1) and to recrystallization (ethyl acetate/hexane) to obtain trans-2-(4-methylphenyl)-N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]cyclohexyl]-6,7-dihydro-5H-benzocycloheptene-8-carboxamide (compound 64) (253 mg) as colorless crystals.

1. stirringthe resulting mixture was stirred for 10 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 ethyl acetate
5. washThe organic layer was washed with an aqueous saturated solution of sodium chloride
6. dry with materialwas dried with anhydrous magnesium sulfate
7. customThe resulting organic layer was evaporated under reduced pressure
8. customto remove the solvent
9. customthe residue was then subjected to purification
10. customto recrystallization (ethyl acetate/hexane)