反应详情

3-(R)-[1-Tert-butoxycarbonylamino-1-(3-pyridyl)methyl]pyrrolidine [F1] (70 mg, 0.252 mmol) was added to an acetonitrile suspension (3 ml) of 5-amino-6,7,8-trifluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (87.0 mg, 0.275 mmol), and the mixture was heated under reflux for 19 hours in the presence of triethylamine (0.3 ml). After cooling, the solvent of the reaction solution was evaporated under a reduced pressure. The resulting residue was dissolved in chloroform (50 ml), this was washed with 10% citric acid (40 ml) and saturated brine (40 ml) and dried over anhydrous sodium sulfate, and then the solvent was evaporated under a reduced pressure. The resulting residue was mixed with concentrated hydrochloric acid (2 ml) under ice-cooling, further mixed with 1 mol/l hydrochloric acid aqueous solution (2 ml) at room temperature and then washed with chloroform (30 ml×4),and the insoluble matter was removed by filtration. This hydrochloric acid solution was adjusted to an alkaline liquid property by adding 10 mol/l sodium hydroxide aqueous solution. This suspension was adjusted to a liquid property of pH 7.4 by adding concentrated hydrochloric acid and 1 mol/l hydrochloric acid and then extracted with chloroform (150 ml×3). The resulting organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated under a reduced pressure to obtain the crude title compound as light yellow crystals. This was purified by recrystallizing from ethanol-aqueous ammonia to obtain 65.1 mg (54%) of the title compound.

1. temperaturethe mixture was heated
2. temperatureAfter cooling
3. customthe solvent of the reaction solution was evaporated under a reduced pressure
4. dissolutionThe resulting residue was dissolved in chloroform (50 ml)
5. washthis was washed with 10% citric acid (40 ml) and saturated brine (40 ml)
6. dry with materialdried over anhydrous sodium sulfate
7. customthe solvent was evaporated under a reduced pressure
8. additionThe resulting residue was mixed with concentrated hydrochloric acid (2 ml) under ice-
9. temperaturecooling
10. additionfurther mixed with 1 mol/l hydrochloric acid aqueous solution (2 ml) at room temperature
11. washwashed with chloroform (30 ml×
12. customthe insoluble matter was removed by filtration
13. additionby adding 10 mol/l sodium hydroxide aqueous solution
14. additionby adding concentrated hydrochloric acid and 1 mol/l hydrochloric acid
15. extractionextracted with chloroform (150 ml×3)
16. dry with materialThe resulting organic layer was dried over anhydrous sodium sulfate
17. customthe solvent was evaporated under a reduced pressure
18. customto obtain the crude title compound as light yellow crystals
19. customThis was purified
20. customby recrystallizing from ethanol-aqueous ammonia