反应详情

温度

80 °C

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).

1. concentrationwas concentrated under reduced pressure
2. dissolutionThe resulting residue was dissolved in dichloromethane (30 ml)
3. washwashed sequentially with water and saturated brine
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customThe resulting residue was purified by silica gel column chromatography (eluant: dichloromethane:acetone=2:1->1:1->dichloromethane:methanol=10:1)
7. dissolutionThe eluted pale yellow solid was dissolved in ethanol (4 mL)
8. additionfollowed by addition of a 10% aqueous solution of sodium hydroxide (4 mL)
9. stirringstirring at 60° C. for 70 min
10. concentrationconcentration under reduced pressure
11. additionThe resulting residue was diluted with water (10 mL)
12. extractionextracted with dichloromethane (2×30 mL)
13. washwashed with saturated brine
14. dry with materialdried over anhydrous sodium sulfate
15. concentrationconcentrated under reduced pressure
16. customThe resulting residue was purified by silica gel column chromatography (eluant: dichloromethane:methanol=10:1)