反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.
实验步骤: Ethyl 7-chloro-6-fluoro-1,4-dihydro-1-(1,1-dimethylethyl)-4-oxo-1,8-naphthyridine-3-carboxylate (327 mg), (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine (174 mg), 1,8-diazabicyclo[5.4.0]undec-7-ene (160 mg) and acetonitrile (5 mL) were mixed together. The reaction mixture was stirred at 80° C. for 1 hour and was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (30 ml), washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluant: dichloromethane:acetone=2:1->1:1->dichloromethane:methanol=10:1). The eluted pale yellow solid was dissolved in ethanol (4 mL), followed by addition of a 10% aqueous solution of sodium hydroxide (4 mL), stirring at 60° C. for 70 min, and concentration under reduced pressure. The resulting residue was diluted with water (10 mL), neutralized with 1 mol/L hydrochloric acid (pH 7.5), and extracted with dichloromethane (2×30 mL). The dichloromethane extracts were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluant: dichloromethane:methanol=10:1) to give 7-[(3S,4S)-3-cyclopropylaminomethyl-4-fluoro-1-pyrrolidinyl]-6-fluoro-1,4-dihydro-1-(1,1-dimethylethyl)-4-oxo-1,8-naphthyridine-3-carboxylic acid as white crystals (141 mg).
was concentrated under reduced pressure
The resulting residue was dissolved in dichloromethane (30 ml)
washed sequentially with water and saturated brine
dried over anhydrous sodium sulfate
concentrated under reduced pressure
The resulting residue was purified by silica gel column chromatography (eluant: dichloromethane:acetone=2:1->1:1->dichloromethane:methanol=10:1)
The eluted pale yellow solid was dissolved in ethanol (4 mL)
followed by addition of a 10% aqueous solution of sodium hydroxide (4 mL)
stirring at 60° C. for 70 min
concentration under reduced pressure
The resulting residue was diluted with water (10 mL)
extracted with dichloromethane (2×30 mL)
washed with saturated brine
dried over anhydrous sodium sulfate
concentrated under reduced pressure
The resulting residue was purified by silica gel column chromatography (eluant: dichloromethane:methanol=10:1)
来源 ID: ord-b79924730fe04d5f84c026f1e8a32040