反应详情

Into a suspension of (E)-3-[4-(4-methylphenyl)-thiophen-2-yl]acrylic acid (150 mg) and 1-hydroxybenzotriazole (124 mg) in acetonitrile (10 ml) was added at room temperature 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (177 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 (276 mg), 1,8-diazabicyclo[5,4,0]-7-undecene (281 mg) and triethylamine (0.17 ml) in acetonitrile (15 ml), and the resulting mixture was stirred for 16 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 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, E)-3-[4-(4-methylphenyl)thiophen-2-yl]-N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]cyclohexyl]acrylamide (compound 72) (191 mg) as colorless crystals.

1. stirringthe resulting mixture was stirred for 16 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 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)