2-Chloro-N,N-dimethylethylamine → HCID 14209191, compound

Participants

Reaction Conditions

Reaction Steps

Sodium hydride (0.3 g) is added in small portions at a temperature in the region of 0° C. to a solution, maintained under an argon atmosphere, of 3-hydroxy-2-(7-methoxy-1,8-naphthyridin-2-yl)-1-isoindolinone (3.1 g) in anhydrous dimethylformamide (40 cc). The suspension obtained is stirred for 45 minutes at a temperature in the region of 0° C. and a 1.4M solution (8.5 cc) of N,N-dimethyl-2-chloroethylamine in toluene is then added. The reaction mixture is heated with stirring to a temperature of 65° C. for 4 hours, and is then cooled to a temperature in the region of 10° C., poured into distilled water (350 cc) and extracted with dichloromethane (3×50 cc). The organic phases are combined, washed with distilled water (4×30 cc), dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. Ethanol (8 cc) heated to 45° C. is added to the oily residue obtained. After removal of a solid by filtration, fumaric acid (1 g) is added to the filtrate and the mixture is heated until dissolution is complete. The solution obtained is cooled to a temperature in the region of 5° C. for 1 hour. The solid formed is separated by filtration, washed with ethanol (2×5 cc), cooled to a temperature in the region of 0° C., and then with diethyl ether (2×20 cc). Distilled water (200 cc) heated to 40° C. is added to the solid obtained. After removal of a solid by filtration, the filtrate is cooled to a temperature in the region of 10° C., saturated aqueous potassium bicarbonate solution is then added to a pH in the region of 9 and the mixture is extracted with ethyl acetate (3×120 cc). The organic phases are combined, washed with distilled water (3×50 cc), dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 60° C. The oily residue obtained is dissolved in ethanol (3 cc) heated to 45° C. Fumaric acid (0.4 g) is added to this solution and the mixture is heated until dissolution is complete. The solid obtained is cooled to a temperature in the region of 5° C. for 1 hour. The solid formed is separated by filtration, washed with ethanol (2×1 cc), cooled to a temperature in the region of 0° C., and then with diethyl ether (2×2 cc), and dried in the air. 3-(2-Dimethylaminoethoxy)-2-(7-methoxy-1,8-naphthyridin-2-yl)-1-isoindolinone fumarate (1.4 g), m.p. 205° C., is thereby obtained.

Provenance & Evidence