反应详情

A mixture of 8-bromo-1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (0.11 g), trans-3-t-butoxycarbonylamino-4-methylpyrrolidine (0.082 g), DBU (0.054 g) and anhydrous acetonitrile (5 ml) was refluxed for 1.5 hours and then concentrated. The resulting residue was dissolved in chloroform (50 ml) and washed with 10% aqueous citric acid solution and water successively. The organic layer was concentrated under reduced pressure and to the oily residue was added methanol to crystallize. The resulting precipitate was collected by filtration, washed with chilled methanol and this was added to concentrated hydrochloric acid-methanol (1:1, 2 ml) and stirred for an hour at room temperature. The reacting mixture was neutralized with concentrated aqueous ammonia, concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography (chloroform:methanol:concentrated aqueous ammonia=20:6:1) and then recrystallized from dichloromethanemethanol (1:1) to give the title compound (0.04 g) as pale yellow powder, mp 186°-190° C. (decompd.).

1. temperaturewas refluxed for 1.5 hours
2. concentrationconcentrated
3. dissolutionThe resulting residue was dissolved in chloroform (50 ml)
4. washwashed with 10% aqueous citric acid solution and water successively
5. concentrationThe organic layer was concentrated under reduced pressure and to the oily residue
6. additionwas added methanol
7. customto crystallize
8. filtrationThe resulting precipitate was collected by filtration
9. washwashed with chilled methanol
10. additionthis was added to concentrated hydrochloric acid-methanol (1:1, 2 ml)
11. concentrationconcentrated under reduced pressure
12. customthe resulting residue was purified by silica gel column chromatography (chloroform:methanol:concentrated aqueous ammonia=20:6:1)
13. customrecrystallized from dichloromethanemethanol (1:1)