反应详情

温度

0 °C

Made 2.25 mmol of 5-bromo-but-2-enoyl chloride by mixing 386 μl (2.25 mmol) trimethylsilyl 4-bromo-but-2-enoate, 10 ml methylene chloride, 294 μl (3.38 mmol) oxalyl chloride, and 2 drops of DMF. After bubbling had subsided, removed solvent and dissolved in 10 ml THF. This solution was added to a mixture of 800 mg (2.25 mmol) 6-amino-4-[(3-bromo-4-fluorophenyl)amino]-3-quinolinecarbonitrile, 50 ml THF, and 392 μl (2.25 mmol) N,N-diisopropylethylamine chilled to 0° C. under N2. At 1 hour, added the mixture dropwise to a solution of 1 ml (11.2 mmol) morpholine in 4.5 ml THF chilled to 0° C. After complete addition, removed the ice bath, and at 2 hours poured onto a mixture of ice and saturated sodium bicarbonate. Extracted with ethyl acetate, dried organic layer with sodium sulfate and reduced solvent to a small volume. Loaded onto a column of silica gel, eluted with 12% methanol/ethyl acetate, stripped solvent from desired fractions and dried in vacuo, giving 369 mg of yellow solid: mass spectrum (electrospray m/e): M+H=509.9, 511.9.

1. customAfter bubbling
2. customremoved solvent
3. dissolutiondissolved in 10 ml THF
4. temperaturechilled to 0° C
5. additionAfter complete addition
6. customremoved the ice bath
7. additionat 2 hours poured onto a mixture of ice and saturated sodium bicarbonate
8. extractionExtracted with ethyl acetate, dried organic layer with sodium sulfate
9. washeluted with 12% methanol/ethyl acetate
10. customdried in vacuo