Water → 2-(7-Methoxy-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 4-methylpentanoate

Participants

Reaction Steps

Triethylamine (27 cc) is added to a solution, maintained at a temperature in the region of 20° C., of 2-(7-methoxy-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinone (12.3 g) in methylene chloride (200 cc). 4-Methylpentanoyl chloride (10.8 g) and 4-dimethylaminopyridine (50 mg) are then introduced dropwise in the course of 20 minutes, and the reaction mixture is then heated for 19 hours under reflux. The suspension obtained in poured into water (800 cc) and the solid obtained is separated by filtration and removed. The organic phase is separated after settling has occurred, washed with water, dried and concentrated to dryness under reduced pressure (2.7 kPa). The oily residue obtained is purified by chromatography on silica gel (0.063-0.2 mm; 150 g) contained in a column 2.7 cm in diameter (eluant: methylene chloride), eluting 50-cc fractions. Fractions 6 to 18 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. After the solid obtained has been recrystallized in acetonitrile, 2-(7-methoxy-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 4-methylpentanoate (4.9 g), m.p. 133° C., is obtained.

Provenance & Evidence