反应详情

To a mixture of 120 mg of 7-methyl-4-oxo-1-(tetrahydro-2H-pyran-4-yl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline-8-carboxylic acid and 2.4 mL of DMF were added 130 mg of 1-(pyridin-3-ylmethyl)piperazine, 0.19 mL of DIPEA, and 177 mg of TBTU, followed by stirring at room temperature overnight. The reaction mixture was ice-cooled and poured into a saturated aqueous sodium hydrogen carbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (chloroform/methanol=100/0-92/8) to obtain white powder. The powder was suspended in 1 mL of methanol, and 0.37 mL of a 4 M hydrogen chloride-ethyl acetate solution was added thereto, followed by stirring for 30 minutes. The obtained powder was collected by filtration, washed with methanol, and then dried under reduced pressure to obtain 82 mg of 7-methyl-8-{[4-(pyridin-3-ylmethyl)piperazin-1-yl]carbonyl}-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one dihydrochloride as a white solid.

1. temperaturecooled
2. extractionfollowed by extraction with ethyl acetate
3. washThe organic layer was washed with saturated brine
4. dry with materialdried over anhydrous magnesium sulfate
5. customThe solvent was evaporated under reduced pressure
6. customthe residue was purified by silica gel column chromatography (chloroform/methanol=100/0-92/8)
7. customto obtain white powder
8. stirringby stirring for 30 minutes
9. filtrationThe obtained powder was collected by filtration
10. washwashed with methanol
11. customdried under reduced pressure