Triethylamine → 4-[(3-Bromophenyl)amino]-7-[3-(1-methylpiperidin-4-yl)propyloxy]-6-[(vinylcarbonyl)amino]quinazoline

Participants

Reaction Conditions

Reaction Steps

To a solution of 300 mg of 6-amino-4-[(3-bromophenyl)amino]-7-[3-(1-methylpiperidin-4-yl)propyloxy]quinazoline in 7 ml of dichloromethane are added 0.28 ml of triethylamine. The reaction mixture is cooled to about −10° C. in an ice/sodium chloride cooling bath. Then a solution of 59 μl of acrylic acid chloride in 1 ml of tetrahydrofuran is added dropwise within 10 minutes. The cooling bath is removed and the mixture is stirred for a further 15 minutes at ambient temperature. For working up, the reaction mixture is poured on to 20 ml of ice water and mixed with 2–3 ml of 2 N sodium hydroxide solution, whereupon a light-colored precipitate is formed. The precipitate is suction filtered, washed with cold water and dissolved in dichloromethane. The solution is dried over sodium sulfate and concentrated by evaporation. The resin-like crude product is purified by chromatography over a silica gel column with methylene chloride/methanol/concentrated ammonia solution (90:10:0.5). Yield: 118 mg (35% of theory); Rf value: 0.35 (silica gel, methylene chloride/methanol/concentrated aqueous ammonia solution=90:10:0.1); mass spectrum (ESI+): m/z=524, 526 [M+H]+.

Provenance & Evidence