Triethylamine → HCID 67490794, compound

Participants

Reaction Conditions

Reaction Steps

Triethylamine (0.277 mL, 1.98 mmol) and 7-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid (185 mg, 0.663 mmol) were added to a solution of (1S,6S)-1-tert-butoxycarbonylamino-8-azabicyclo[4.3.0]nonane (175 mg, 0.728 mmol) in dimethyl sulfoxide (1.33 mL) in a nitrogen atmosphere, and the mixture was stirred at 75° C. for 12 days. The reaction solution was diluted with ethyl acetate (45 mL) and then washed with a 10% citric acid solution (40 mL), water (40 mL), and a saturated sodium hydroxide solution (40 mL). The organic layer was dried over anhydrous sodium sulfate and filtered, and then the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform:methanol=100:0→99:1→98:2). 260 mg (0.578 mmol) of the resulting residue was dissolved in concentrated hydrochloric acid (2.5 mL) under ice-cooling, and the solution was stirred at room temperature for 10 minutes. After washing with chloroform (50 mL×2), 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 (100 mL×2) and chloroform/methanol=10/1 (100 mL). The organic layer was dried over anhydrous sodium sulfate and filtered, and then the filtrate was concentrated under reduced pressure. The resulting residue was purified by PTLC (developed with the lower layer of chloroform/methanol/water=7/3/1). After the fluorescent part was collected, the lower layer of chloroform/methanol/water=7/3/1 (70 mL) was added. After ultrasonic treatment, the silica gel was filtered off. The filtrate was concentrated under reduced pressure and then vacuum dried. Ethanol (1 mL), diethyl ether, and 2-propanol were added to the residue. Diethyl ether was added. After repeating ultrasonic treatment and ice-cooling several times, the mixture was stirred at 40° C. for 30 minutes. After stirring at room temperature for two hours, the crystals were collected by filtration and dried under reduced pressure to give 88.7 mg of the title compound as pale yellow crystals.

Provenance & Evidence