Acetonitrile → 5-Amino-7-{3-(R)-[1-amino-1-(2-pyridyl)methyl]-1-pyrrolidinyl}-6,8-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

3-(R)-[1-Tert-butoxycarbonylamino-1-(2-pyridyl)methyl]pyrrolidine [F2] (0.535 mmol) was added to an acetonitrile suspension (5 ml) of 5-amino-6,7,8-trifluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (169 mg, 0.534 mmol), and the mixture was heated under reflux for 19 hours in the presence of triethylamine (0.5 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 (5 ml) under ice-cooling, further mixed with 1 mol/l hydrochloric acid aqueous solution (5 ml) at roam temperature and then washed with chloroform (50 ml×5). This hydrochloric acid aqueous solution was adjusted to an alkaline liquid property by adding 10 mol/l sodium hydroxide aqueous solution and then stirred at room temperature for 1 hour. 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 to obtain 136 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 (5 ml) under ice-
9. temperaturecooling
10. additionfurther mixed with 1 mol/l hydrochloric acid aqueous solution (5 ml) at roam temperature
11. washwashed with chloroform (50 ml×5)
12. additionby adding 10 mol/l sodium hydroxide aqueous solution
13. additionby adding concentrated hydrochloric acid and 1 mol/l hydrochloric acid
14. extractionextracted with chloroform (150 ml×3)
15. dry with materialThe resulting organic layer was dried over anhydrous sodium sulfate
16. customthe solvent was evaporated under a reduced pressure
17. customto obtain the crude title compound as light yellow crystals
18. customThis was purified
19. customby recrystallizing from ethanol

ORD record

ord-20d7d09c94cb43ab8a250715c17bf336

Source dataset

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07186843B2