5-Methyl-2-hexanone → 2-(7-Methoxy-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

An oily suspension (50% by weight; 0.5 g) of sodium hydride is added in small portions at a temperature in the region of -5° C. to a solution, maintained under an argon atmosphere, of 3-hydroxy-2-(7-methoxy-1,8-naphthyridin-2-yl)-1-isoindolinone (1.6 g) in anhydrous dimethylformamide (20 cc), and the suspension obtained is stirred for 30 minutes at a temperature in the region of -5° C. A solution of 5-methyl-2-hexanone (1.2 g) in anhydrous dimethylformamide (5 cc) is then added and stirring is continued for 5 hours at a temperature in the region of 20° C. The reaction mixture is then poured into distilled water (200 cc) and extracted with dichloromethane (3×100 cc). The organic phases are combined, washed with distilled water (5×20 cc) and then concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. The oily residue obtained is purified by chromatography on silica gel (15 g) contained in a column 1.5 cm in diameter [eluent: dichloromethane/methanol (99:1 by volume)]. Elution is first performed with 30 cc of solvent: the corresponding eluate is discarded; elution is then performed with 100 cc of solvent: the corresponding eluate is concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. The residue obtained is recrystallized in ethyl acetate; 2-(7-methoxy-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone (1.3 g), m.p. 150° C., is thereby obtained.

Herkunft & Nachweise