Water → [2-(7-methoxy-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyloxy]-N-cyclohexylacetamide

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence