反应详情

To a mixture of 5-(3-aminophenoxy)-6-(2-hydroxypropan-2-yl)-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (27 mg), diisopropylethylamine (29 μL), and chloroform (5 ml) was added acryloyl chloride (7 μL) under ice-cooling, followed by stirring for 30 minutes. Further acryloyl chloride (7 μL) was added, followed by stirring under ice-cooling for 30 minutes. Diisopropylethylamine (29 μl) and acryloyl chloride (7 μL) were added thereto, followed by stirring for 30 minutes under ice-cooling. A saturated aqueous sodium hydrogen carbonate solution (10 mL) and tetrahydrofuran (20 mL) were added thereto under ice-cooling, followed by stirring for 10 minutes under ice-cooling. To the reaction mixture was added a 1 M aqueous sodium hydroxide solution (2 mL), followed by stirring at room temperature for 30 minutes. The reaction mixture was subjected to liquid separation and to the organic phase was added silica gel. Then, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-200:10:1), washed with ethyl acetate, and the solid was collected by filtration and then dried under reduced pressure to obtain 5-[3-(acryloylamino)phenoxy]-6-(2-hydroxypropan-2-yl)-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (18 mg) as a yellow solid.

1. temperaturecooling
2. stirringby stirring under ice-
3. temperaturecooling for 30 minutes
4. stirringby stirring for 30 minutes under ice-
5. temperaturecooling
6. temperatureunder ice-cooling
7. stirringby stirring for 10 minutes under ice-
8. temperaturecooling
9. stirringby stirring at room temperature for 30 minutes
10. customThe reaction mixture was subjected to liquid separation and to the organic phase
11. additionwas added silica gel
12. customThen, the solvent was evaporated under reduced pressure
13. customThe residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-200:10:1)
14. washwashed with ethyl acetate
15. filtrationthe solid was collected by filtration
16. customdried under reduced pressure