Morpholine → N-{4-[(3-Bromo-4-fluorophenyl)amino]-3-cyano-7-methoxy-6-quinolinyl}-4-morpholino-2-butenamide

Participants

Reaction Conditions

Reaction Steps

Made 2.07 mmol of 5-bromo-but-2-enoyl chloride by mixing 363 μl (2.07 mmol) trimethylsilyl 4-bromo-but-2-enoate, 8 ml methylene chloride, 270 μl (3.10 mmol) oxalyl chloride and 2 drops of DMF. Removed solvent when bubbling subsided and dissolved in 10 ml THF. The acid chloride solution was added to a mixture of 800 mg A (2.07 mmol) 6-amino-4-[(3-bromo-4-fluorophenyl)amino]-7-methoxy-3-quinolinecarbonitrile, 50 ml THF, and 721 μl (4.14 mmol) N,N-diisopropylethylamine chilled to 0° C. under N2. At 1.5 hours added this mixture to a solution of 900 g (10.4 mmol) morpholine in 4.3 ml THF at 0° C. Warmed to 25° C. after complete addition, and at 2 hours added 900 μl more morpholine. At 3 hours, poured onto a mixture of ice and saturated sodium bicarbonate, extracted with ethyl acetate, dried with sodium sulfate, and reduced solvent to a small volume. Loaded compound onto a column of silica gel, eluted with 12% methanol/ethyl acetate, stripped solvent from desired fractions, and dried in vacuo, giving 287 mg of orange-brown solid: mass spectrum (electrospray m/e): M+H=539.9, 541.9.

Provenance & Evidence