反应详情

After adding 3-(R)-[1-tert-butoxycarbonylaminocyclopropyl]pyrrolidine (185 mg, 817 μmol) and triethylamine (0.50 ml) to dried dimethyl sulfoxide (2 ml), 7-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid (190 mg, 68 μmol) was added thereto and it was heated under reflux for 17 hours under a nitrogen atmosphere. After concentrating the reaction solution under a reduced pressure, the residue was dissolved in chloroform (50 ml). After washing the organic layer with a 10% aqueous citric acid solution (25 ml), the organic layer was dried over anhydrous sodium sulfate. After filtering, the filtrate was concentrated under a reduced pressure, and after adding dropwise concentrated hydrochloric acid (5 ml) to the residue while cooling with ice, stirring at room temperature was performed for 30 minutes. 1 mol/l Hydrochloric acid (5 ml) was then added to the reaction solution, and after washing the yellow acidic aqueous solution with chloroform (20 ml×3), the pH was adjusted to 12.0 with an aqueous sodium hydroxide solution and the insolubles were removed by filtration. After adjusting the pH of the basic aqueous solution to 7.4 using 1 mol/l hydrochloric acid, extraction with chloroform (100 ml×4) was performed. After drying over anhydrous sodium sulfate, the solvent was evapolated under a reduced pressure. The residue thus obtained was purified by preparative chromatography (development at the lower layer of a 7:3:1 mixture of chloroform:methanol:water), recrystallized in ethanol, and dried under a reduced pressure. 112 mg (43%) of the title compound was thereby obtained in the form of yellow crystals.

1. additionwas added
2. temperatureit was heated
3. temperatureunder reflux for 17 hours under a nitrogen atmosphere
4. concentrationAfter concentrating the reaction solution under a reduced pressure
5. dissolutionthe residue was dissolved in chloroform (50 ml)
6. washAfter washing the organic layer with a 10% aqueous citric acid solution (25 ml)
7. dry with materialthe organic layer was dried over anhydrous sodium sulfate
8. filtrationAfter filtering
9. concentrationthe filtrate was concentrated under a reduced pressure
10. additionafter adding dropwise concentrated hydrochloric acid (5 ml) to the residue
11. temperaturewhile cooling with ice
12. addition1 mol/l Hydrochloric acid (5 ml) was then added to the reaction solution
13. washafter washing the yellow acidic aqueous solution with chloroform (20 ml×3)
14. customthe insolubles were removed by filtration
15. extractionto 7.4 using 1 mol/l hydrochloric acid, extraction with chloroform (100 ml×4)
16. dry with materialAfter drying over anhydrous sodium sulfate
17. customThe residue thus obtained
18. customwas purified by preparative chromatography (development
19. additionat the lower layer of a 7:3:1 mixture of chloroform
20. custommethanol:water), recrystallized in ethanol
21. customdried under a reduced pressure