反应详情

3-Benzyloxy-5-bromo-1-(2-hydroxyethyl)-4-oxo-1,4-dihydropyridine-2-carboxylic acid 3-chlorobenzylamide (1.75 g) was suspended in tetrahydrofuran (50 ml), and N,N-diisopropylethylamine (3.72 ml) and methanesulfonyl chloride (1.38 ml) were added. After stirring at room temperature for 1 hr, 0.5N aqueous hydrochloric acid (40 ml) was added, and the mixture was extracted twice with ethyl acetate (100 ml each). The ethyl acetate layer was washed with aqueous sodium hydrogen carbonate, dried and concentrated. The obtained residue was dissolved in dimethylformamide (50 ml) and 60% sodium hydride was added by small portions with stirring at room temperature. After confirming the completion of the reaction by thin layer chromatography (TLC), the reaction mixture was ice-cooled, 0.33N aqueous hydrochloric acid (300 ml) was added, and the mixture was extracted twice with ethyl acetate (250 ml each). The ethyl acetate layer was washed with water, dried, concentrated, and crystallized from ethyl acetate-hexane to give 9-benzyloxy-7-bromo-2-(3-chlorobenzyl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,8-dione (1.58 g).

1. extractionthe mixture was extracted twice with ethyl acetate (100 ml each)
2. washThe ethyl acetate layer was washed with aqueous sodium hydrogen carbonate
3. customdried
4. concentrationconcentrated
5. dissolutionThe obtained residue was dissolved in dimethylformamide (50 ml)
6. addition60% sodium hydride was added by small portions
7. stirringwith stirring at room temperature
8. customthe completion of the reaction by thin layer chromatography (TLC)
9. temperaturecooled
10. extractionthe mixture was extracted twice with ethyl acetate (250 ml each)
11. washThe ethyl acetate layer was washed with water
12. customdried
13. concentrationconcentrated
14. customcrystallized from ethyl acetate-hexane