反应详情

To a mixture of trans-4-dimethylaminocrotonic acid hydrochloride (113 mg) and acetonitrile (1.9 mL) were added oxalyl dichloride (55 μL) and N,N-dimethylformamide (2 droplets) under ice-cooling, followed by stirring at room temperature for 2 hours. To a mixture of 5-(3-aminophenoxy)-6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (190 mg) and N-methylpyrrolidone (3.8 mL) was added a solution of the acid chloride prepared above under ice-cooling, followed by stirring at room temperature overnight. The reaction mixture was diluted with ethyl acetate, and then washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine. The organic phase was dried over anhydrous magnesium sulfate and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-100:10:1). Ethyl acetate was added thereto and the precipitated solid was collected by filtration and then dried under reduced pressure to obtain 5-(3-{[(2E)-4-(dimethylamino)buta-2-enoyl]amino}phenoxy)-6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (107 mg) as a pale yellow solid.

1. temperaturecooling
2. customprepared above under ice-
3. temperaturecooling
4. stirringby stirring at room temperature overnight
5. washwashed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine
6. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
7. customthe solvent was evaporated under reduced pressure
8. customThe residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-100:10:1)
9. additionEthyl acetate was added
10. filtrationthe precipitated solid was collected by filtration
11. customdried under reduced pressure