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

Participants

Reaction Steps

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.

Provenance & Evidence