反应详情

To a mixture of 5-(3-aminophenoxy)-6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (2 g), diisopropylethylamine (1.53 mL), and chloroform (100 mL) was added acryloyl chloride (508 μL) under ice-cooling, followed by stirring for 1 hour. Acryloyl chloride (363 μL) was added thereto, followed by stirring for 1 hour. The mixture was subject to liquid separation by the addition of chloroform and a saturated aqueous sodium hydrogen carbonate solution, and the organic phase was washed with saturated brine and then dried over anhydrous magnesium sulfate. The solvent was concentrated and the obtained residue was purified by silica gel column chromatography (chloroform:methanol:28% aqueous ammonia=1:0:0-200:10:1). Ethyl acetate was added thereto, the solid was collected by filtration and then dried under reduced pressure to obtain 5-[3-(acryloylamino)phenoxy]-6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (1.6 g) as a pale yellow solid.

1. temperaturecooling
2. stirringby stirring for 1 hour
3. customThe mixture was subject to liquid separation by the addition of chloroform
4. washa saturated aqueous sodium hydrogen carbonate solution, and the organic phase was washed with saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. concentrationThe solvent was concentrated
7. customthe obtained residue was purified by silica gel column chromatography (chloroform:methanol:28% aqueous ammonia=1:0:0-200:10:1)
8. additionEthyl acetate was added
9. filtrationthe solid was collected by filtration
10. customdried under reduced pressure