3-(Chloromethyl)pyridine → HCID 14209197, compound

Participants

Reaction Conditions

Reaction Steps

An oily suspension (50% by weight; 1.2 g) of sodium hydride 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 (6.2 g) in anhydrous dimethylformamide (100 cc). The suspension obtained is stirred for 30 minutes at a temperature in the region of 0° C. and a 1.4M solution (16 cc) of 3-chloromethylpyridine in toluene is then added. The reaction mixture is heated with stirring to a temperature of 70° C. for 1 hour, then cooled to a temperature in the region of 10° C., poured into distilled water (600 cc) and extracted with dichloromethane (3×200 cc). The organic phases are combined, washed with distilled water (4×50 cc), dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. 1N aqueous hydrochloric acid solution (30 cc) is added to the residue obtained. After removal of a solid by filtration, the filtrate is alkalinized with 10N aqueous sodium hydroxide solution to a pH in the region of 11, and extracted with dichloromethane (3×150 cc). The organic phases are combined, washed with distilled water (3×25 cc), dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. After recrystallization in acetonitrile, 2-(7-methoxy-1,8-naphthyridin-2-yl)-3-[(3-pyridyl)methoxy]-1-isoindolinone (3.7 g), m.p. 175° C., is obtained.

Provenance & Evidence