反应详情

To a mixture of 6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-5-(1,2,3,6-tetrahydropyridin-4-yl)pyrazin-2-carboxamide (40 mg), diisopropylethylamine (75 μL), and chloroform (4 mL) was added under ice-cooling acryloyl chloride (25 μL), followed by stirring at room temperature overnight. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution, followed by extraction with chloroform. The organic phase was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-100:10:1). To an ethyl acetate solution of the obtained oily substance was added 4 M hydrogen chloride ethyl acetate solution, followed by stirring for 5 hours. The solvent was evaporated under reduced pressure and the obtained solid was washed with diisopropyl ether to obtain 5-(1-acryloyl-1,2,3,6-tetrahydropyridin-4-yl)-6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazin-2-carboxamide monohydrochloride (21 mg) as an orange solid.

1. additionwas added under ice-
2. extractionfollowed by extraction with chloroform
3. washThe organic phase was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine
4. dry with materialdried over anhydrous magnesium sulfate
5. customthe solvent was evaporated under reduced pressure
6. customThe obtained residue was purified by silica gel chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-100:10:1)
7. additionTo an ethyl acetate solution of the obtained oily substance was added 4 M hydrogen chloride ethyl acetate solution
8. stirringby stirring for 5 hours
9. customThe solvent was evaporated under reduced pressure
10. washthe obtained solid was washed with diisopropyl ether