Dimethylamine → N-{4-[(3-Chloro-4-fluorophenyl)amino]-3-cyano-6-quinolinyl}-4-dimethylamino-2-butenamide

Participants

Reaction Conditions

Reaction Steps

Dissolved 1.50 g (4.80 mmol) 6-amino-4-[(3-chloro-4-fluorophenyl)amino]-3-quinolinecarbonitrile in 50 ml THF, added 836 μl (4.80 mmol) N,N-diisopropylethylamine, and chilled to 0° C. under N2. Added 500 μl (4.80 mmol) 4-bromo-but-2-enoyl chloride and after 1 hour dropwise added the mixture to 10 ml of a 2M solution (19 mmol) of dimethylamine in THF cooled to -78° C. At 2 hours, added 5 ml (9.5 mmol) more of dimethyl amine solution and warmed to 25° C. After 1 hour, poured onto a cold solution of sodium bicarbonate. Extracted with ethyl acetate, dried organics with brine and sodium sulfate, reduced to small volume and loaded onto a column of silica gel. Eluted with 70% methanol/ethyl acetate, stripped solvent of desired fractions and dried in vacuo, giving 427 mg of yellow solid: mass spectrum (electrospray m/e): M+H=424.0, 426.0.

Provenance & Evidence