反应详情

To a solution of 5-benzyloxy-6-(3-chlorobenzylcarbamoyl)-1-(2,2-dimethoxyethyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid (25.4 mg) obtained in Example 161, Step 4 in tetrahydrofuran (0.3 ml) were successively added triethylamine (0.021 ml) and thionyl chloride (0.0056 ml) at 0° C. with stirring. After stirring at room temperature for 10 min, the mixture was ice-cooled again and isopropylamine (0.0086 ml) was added. After stirring at room temperature for 30 min, 5% aqueous potassium hydrogen sulfite solution was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried and concentrated. Trifluoroacetic acid was added to the obtained residue and the mixture was stirred at 70° C. for 5.5, hr. Trifluoroacetic acid was evaporated, toluene was added and the mixture was concentrated, which operations were performed twice. Crystallization from ethyl acetate (2 ml) gave 2-(3-chlorobenzyl)-9-hydroxy-1,8-dioxo-1,8-dihydro-2H-pyrido[1,2-a]pyrazine-7-carboxylic acid isopropylamide (13.6 mg)

1. customat 0° C.
2. stirringAfter stirring at room temperature for 10 min
3. temperaturecooled again
4. stirringAfter stirring at room temperature for 30 min
5. extractionthe mixture was extracted with ethyl acetate
6. washThe ethyl acetate layer was washed with brine
7. customdried
8. concentrationconcentrated
9. additionTrifluoroacetic acid was added to the obtained residue
10. stirringthe mixture was stirred at 70° C. for 5.5, hr
11. customTrifluoroacetic acid was evaporated
12. additiontoluene was added
13. concentrationthe mixture was concentrated
14. customCrystallization from ethyl acetate (2 ml)