反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
PROCEDURE
实验过程
Added to a solution of 33 mg of 7-methyl-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid in 0.5 cm3 of anhydrous dimethylformamide are 0.05 cm3 of triethylamine and 51 mg of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)butan-2-ol hydrochloride (2:1), then 17 mg of 1-hydroxy-7-azabenzotriazole and 24 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. The solution is kept stirring for 15 h at a temperature close to 20° C. 20 cm3 of water and 30 cm3 of ethyl acetate are added to the reaction medium. After decanting, the organic phase is washed with 20 cm3 of a saturated aqueous solution of ammonium chloride, five lots of 20 cm3 of water, then 20 cm3 of a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure (5 kPa). The residue is dissolved in 2 cm3 of dichloromethane then purified by flash chromatography over silica (column: 15 g; spherical silica of BP-SUP type, particle size: 20-40 μm; eluent: 60% heptane/40% ethyl acetate). After concentrating the fractions under reduced pressure, 68 mg of N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)propyl]-7-methyl-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide are obtained in the form of a colorless oil.
WORKUP
后处理
- customclose to 20° C
- customAfter decanting
- washthe organic phase is washed with 20 cm3 of a saturated aqueous solution of ammonium chloride, five lots of 20 cm3 of water
- dry with material20 cm3 of a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate
- filtrationfiltered
- concentrationconcentrated to dryness under reduced pressure (5 kPa)
- dissolutionThe residue is dissolved in 2 cm3 of dichloromethane
- customthen purified by flash chromatography over silica (column: 15 g; spherical silica of BP-SUP type, particle size: 20-40 μm; eluent: 60% heptane/40% ethyl acetate)
- concentrationAfter concentrating the fractions under reduced pressure, 68 mg of N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)propyl]-7-methyl-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide
- customare obtained in the form of a colorless oil