反应详情

1,4-Diazabicyclo[2.2.2]octane (522 mg, 4.65 mmol, 1.0 eq) is added at room temperature to a stirred suspension of 3-hydroxy-6-methoxy-[1,5]naphthyridine-4-carbaldehyde (950 mg, 4.65 mmol, 1.0 eq) in acrylic acid methyl ester (20 mL) and the resulting mixture is heated under reflux for 3 hours. The reaction mixture is then cooled down to room temperature, solvent is removed and the residue is dissolved in 1,2-dichloroethane (20 mL). Triethylamine (19.5 mL, 139.6 mmol, 30.0 eq) is then added at 0° C., followed by methanesulfonyl chloride (3.85 mL, 69.8 mml, 15.0 eq) and the resulting mixture is heated under reflux for 4 hours. Solvent is removed and the residue is extracted with dichloromethane (3×40 mL) and water (40 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by column chromatography (silica gel, eluent: petroleum ether:ethyl acetate, 10:1 to 5:1, v/v) to afford 6-methoxy-2H-1-oxa-5,9-diaza-phenanthrene-3-carboxylic acid methyl ester as a light yellow oil (670 mg, 53% yield).

1. temperaturethe resulting mixture is heated
2. temperatureunder reflux for 3 hours
3. customsolvent is removed
4. dissolutionthe residue is dissolved in 1,2-dichloroethane (20 mL)
5. temperaturethe resulting mixture is heated
6. temperatureunder reflux for 4 hours
7. customSolvent is removed
8. extractionthe residue is extracted with dichloromethane (3×40 mL) and water (40 mL)
9. dry with materialThe combined organic layers are dried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customto give a residue that
13. customis purified by column chromatography (silica gel, eluent