反应详情

Poured into a suspension of 233 mg of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)butan-2-ol hydrochloride (2:1), 278 mg of 7-[methyl(methylsulfonyl)amino]-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid, 12 mg of hydroxybenzotriazole and 142 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in 10 cm3 of dichloromethane is 0.4 cm3 of N,N-diisopropylethylamine at a temperature close to 20° C. The solution is kept stirring for 20 h at a temperature close to 20° C. 20 cm3 of water are added to the reaction medium. After decanting, the organic phase is filtered through a pellet of 15 g of 40-63 μm silica. The silica pellet is washed firstly with 150 cm3 of dichloromethane then secondly with 150 cm3 of a mixture of 50% ethyl acetate/50% dichloromethane. This second filtrate is concentrated using a rotary evaporator under reduced pressure (5 kPa). 330 mg of N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)propyl]-7-[methyl(methylsulfonyl)amino]-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide are obtained in the form of a white foam.

1. customclose to 20° C
2. customclose to 20° C
3. customAfter decanting
4. filtrationthe organic phase is filtered through a pellet of 15 g of 40-63 μm silica
5. washThe silica pellet is washed firstly with 150 cm3 of dichloromethane
6. concentrationThis second filtrate is concentrated
7. customa rotary evaporator under reduced pressure (5 kPa)