Sodium Carbonate → 4-(4-Chloro-2-fluoro-5-hydroxy-phenylamino)-5,8-dimethoxy-quinoline-3-carbonitrile

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Reaction Conditions

Reaction Steps

A mixture of 0.223 g of 4-chloro-5,8-dimethoxy-3-quinolinecarbonitrile, 0.22 g of the methyl carbonate of 4-chloro-2-fluoro-5-hydroxy-aniline, and 15 ml of ethoxyethanol was stirred under nitrogen, at reflux temperature for 30 minutes. The mixture was cooled and added to 100 ml of water. To this mixture was added sodium carbonate to pH 9. The product was collected, washed with water, and dried. The solids thus obtained were dissolved in a mixture of 30 ml of methyl alcohol and 20 ml of acetone. To this mixture was added 1.5 ml of 28-30% ammonium hydroxide solution. The mixture was heated at 50° C. for 30 minutes and concentrated. The product was collected, washed with ethyl acetate, and dried to give 0.237 g of 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-5,8-dimethoxy-quinoline-3-carbonitrile as a solid, mp 240° C. (decomposed); mass spectrum (electrospray, m/e): M+H 373.9.

Provenance & Evidence