反应详情

温度

80 °C

An oily suspension (50% by weight; 2.1 g) of sodium hydride is added at a temperature in the region of 0° C. to a solution, maintained under a nitrogen atmosphere, of 3-hydroxy-2-(7-methoxy-1,8-naphthyridin-2-yl)-1-isoindolinone (12.3 g) in anhydrous dimethylformamide (150 cc). The suspension obtained is stirred for 45 minutes at a temperature in the region of 0° C., N-(cyclohexyl)chloroacetamide (7.7 g) is then added and the mixture is heated to 80° C. for 18 hours. After being cooled, the reaction mixture is poured into water (700 cc) and the precipitate obtained is separated by filtration, washed with water and dried in the air. The solid obtained is purified by chromatography on silica (0.063-0.2 mm; 220 g) contained in a column 4 cm in diameter (eluant: methylene chloride), collecting 50-cc fractions. Fractions 41 to 60 are combined and concentrated to dryness under reduced pressure (2.7 kPa). By recrystallization of the residue obtained in acetonitrile, [2-(7-methoxy-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyloxy]-N-cyclohexylacetamide (1.8 g), m.p. 175° C., is obtained.

1. customThe suspension obtained
2. additionis then added
3. temperatureAfter being cooled
4. customthe precipitate obtained
5. customis separated by filtration
6. washwashed with water
7. customdried in the air
8. customThe solid obtained
9. customis purified by chromatography on silica (0.063-0.2 mm; 220 g)
10. customcollecting 50-cc fractions
11. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
12. customBy recrystallization of the residue
13. customobtained in acetonitrile