反应详情

(Step 2) A solution of 2-amino-5-chloronicotinamide (685 mg) and 4-(bromomethyl)-1-fluoro-2-(methylsulfonyl)benzene obtained in Step 1 (1.6 g) in DMF (10 ml) was stirred at 90° C. for 24 hr. The mixture was allowed to cool to room temperature, methanol and ethyl acetate were added, and the precipitated crystals were collected by filtration. The obtained crystals were dissolved in 1N sodium hydroxide solution, and the solution was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=4:1). The obtained yellow solid was dissolved in methanol, 4N hydrogen chloride-ethyl acetate solution (2 ml) was added, and the precipitated crystals were collected by filtration, and recrystallized to give the title compound (510 mg).

1. filtrationthe precipitated crystals were collected by filtration
2. dissolutionThe obtained crystals were dissolved in 1N sodium hydroxide solution
3. extractionthe solution was extracted with ethyl acetate
4. washThe organic layer was washed with saturated brine
5. dry with materialdried over magnesium sulfate
6. customThe solvent was evaporated under reduced pressure
7. customThe residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=4:1)
8. dissolutionThe obtained yellow solid was dissolved in methanol
9. addition4N hydrogen chloride-ethyl acetate solution (2 ml) was added
10. filtrationthe precipitated crystals were collected by filtration
11. customrecrystallized