1-Methylpyrrolidine → HCID 67490977, compound

Participants

Reaction Steps

N-methylpyrrolidine (0.246 mL, 2.37 mmol) and 1-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (306 mg, 0.79 mmol) were added to a solution of (1R,5S)-1-(tert-butoxycarbonylamino)-5-fluoro-3-azabicyclo[3.3.0]octane (193 mg, 0.79 mmol) in acetonitrile (10.0 mL), and the mixture was heated to reflux for 10 hours. 1-(6-Amino-3,5-difluoropyridin-2-yl)-8-chloro-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (92 mg, 0.24 mmol) was added again to the reaction solution, and the mixture was further heated to reflux for 4.5 hours. The solvent was evaporated under reduced pressure, and then the residue was extracted with a 10% citric acid solution and ethyl acetate. Then, the organic layer was washed with water twice and brine, dried over anhydrous sodium sulfate, and filtered. Thereafter, the solvent was evaporated under reduced pressure. The resulting residue was subjected to silica gel column chromatography (dichloromethane:methanol=99:1). The resulting oil (409 mg) was dissolved in concentrated hydrochloric acid (3.0 mL) under ice-cooling, and the solution was stirred at room temperature for 2.5 hours. The reaction solution was washed with chloroform twice, and then the aqueous layer was adjusted to pH 12 with a saturated sodium hydroxide solution. The basic solution was adjusted to pH 7.4 with hydrochloric acid, followed by extraction with chloroform. The organic layer was dried over anhydrous sodium sulfate and filtered, and then the solvent was evaporated under reduced pressure. Chloroform was added to the residue, and the insoluble material was removed by filtration. Then, the filtrate was evaporated under reduced pressure, and the resulting residue was purified by recrystallization from ethanol to give 47 mg of the title compound as a pale yellow solid.

Provenance & Evidence