反应详情

To a solution of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[[1-(carboxymethyl)-1H-pyrazol-4-yl]methyl]-2-(3,4-dimethylbenzyl)piperazine (120 mg) in tetrahydrofuran (1 ml) were added 1-hydroxybenzotriazole hydrate (176 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (240 mg) and morpholine (0.11 ml) at room temperature, and the mixture was stirred at room temperature overnight. The mixture was quenched with water, and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and evaporated under reduced pressure. The residue was purified by column chromatography on a silica gel using a mixture of methanol and ethyl acetate (1:9) as eluent to give a crude oil (76.7 mg). The oil was dissolved in ethyl acetate (0.7 ml) and added 4N hydrogen chloride in ethyl acetate (0.15 ml) at room temperature. After the addition of isopropyl ether, the resulting precipitate was filtered off and dried under reduced pressure to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[[1-(morpholinocarboxymethyl)-1H-pyrazol-4-yl]methyl]piperazine hydrochloride (40 mg) as a powder.

1. customThe mixture was quenched with water
2. extractionextracted with ethyl acetate
3. washThe organic layer was washed with brine
4. dry with materialdried over magnesium sulfate
5. customevaporated under reduced pressure
6. customThe residue was purified by column chromatography on a silica gel using
7. additiona mixture of methanol and ethyl acetate (1:9) as eluent
8. customto give a crude oil (76.7 mg)
9. filtrationthe resulting precipitate was filtered off
10. customdried under reduced pressure