反应详情

To a solution of 700 mg of (3RS,4RS)-3-(2,4-dichlorophenyl)-2-{(1SR,2SR)-2-[(methylsulfonyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid, 351 mg of 1-phenylmethanesulfonamide, and 334 mg of DMAP in 10.5 ml of DMF was added 525 mg of WSC/hydrochloride, followed by stirring at room temperature overnight. 0.1 M hydrochloric acid was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, then dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: chloroform-methanol), and ethyl acetate and a saturated aqueous sodium hydrogen carbonate solution were then added thereto for liquid separation. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. Ethyl acetate and diisopropyl ether were added thereto, and the precipitated solid was collected by filtration to obtain 33 mg of (3RS,4RS)—N-(benzylsulfonyl)-3-(2,4-dichlorophenyl)-2-{(1SR,2SR)-2-[(methylsulfonyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide as a colorless solid.

1. extractionfollowed by extraction with ethyl acetate
2. washThe organic layer was washed with a saturated aqueous sodium chloride solution
3. dry with materialdried over anhydrous magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. customThe residue was purified by silica gel column chromatography (eluent: chloroform-methanol), and ethyl acetate
6. additiona saturated aqueous sodium hydrogen carbonate solution were then added
7. customfor liquid separation
8. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
9. concentrationconcentrated under reduced pressure
10. additionEthyl acetate and diisopropyl ether were added
11. filtrationthe precipitated solid was collected by filtration