反应详情

Into a suspension of (E)-3-[5-(4-methylphenyl)-thiophen-2-yl]acrylic acid (200 mg) and 1-hydroxybenzotriazole (166 mg) in acetonitrile (10 ml) was added at room temperature 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (235 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 (368 mg), triethylamine (0.23 ml) and 1,8-diazabicyclo[5,4,0]-7-undecene (374 mg) in acetonitrile (10 ml), and the resulting mixture was stirred further for 18 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 1:1) and to recrystallization (ethanol/ethyl acetate) to obtain trans-(E)-N-[4-(N-methyl-N-(tetrahydropyran-4-yl)aminomethylcyclohexyl]-3-[5-(4-methylphenyl)thiophen-2-yl]acrylamide (compound 71) (246 mg) as yellow crystals.

1. stirringthe resulting mixture was stirred further for 18 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/ethyl acetate)