反应详情

温度

60 °C

tert-Butyl (2-{methyl[3-(2-piperazin-1-ylpyrimidin-5-yl)benzyl]amino}-2-oxoethyl)carbamate (250 mg) was dissolved in dichloroethane (3 ml), and 3-hydroxy-2,2-dimethylpropionic acid (74 mg), WSC hydrochloride (131 mg), and HOBt (92 mg) were added thereto, followed by stirring at 60° C. for 6 hours. To the reaction mixture was added water, followed by extraction with CHCl3. After drying over Na2SO4, the solvent was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (CHCl3/MeOH). The product was dissolved in EtOH (3 ml), and 4 M hydrogen chloride/EtOAc (1 ml) was added thereto, followed by stirring at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and then a saturated aqueous sodium hydrogen carbonate solution was added thereto, followed by extraction with CHCl3. The organic layer was dried over Na2SO4 and the solvent was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (CHCl3/MeOH). The product was dissolved in EtOH (3 ml), and L-tartaric acid (27 mg) was added thereto, followed by stirring at room temperature overnight. The precipitated solid was collected by filtration to obtain N-(3-{2-[4-(3-hydroxy-2,2-dimethylpropanoyl)piperazin-1-yl]pyrimidin-5-yl}benzyl)-N-methylglycinamide L-tartrate (62 mg).

1. extractionfollowed by extraction with CHCl3
2. dry with materialAfter drying over Na2SO4
3. concentrationthe solvent was concentrated under reduced pressure
4. customThe obtained residue was purified by silica gel column chromatography (CHCl3/MeOH)
5. dissolutionThe product was dissolved in EtOH (3 ml)
6. addition4 M hydrogen chloride/EtOAc (1 ml) was added
7. stirringby stirring at room temperature overnight
8. concentrationThe reaction mixture was concentrated under reduced pressure
9. additiona saturated aqueous sodium hydrogen carbonate solution was added
10. extractionfollowed by extraction with CHCl3
11. dry with materialThe organic layer was dried over Na2SO4
12. concentrationthe solvent was concentrated under reduced pressure
13. customThe obtained residue was purified by silica gel column chromatography (CHCl3/MeOH)
14. dissolutionThe product was dissolved in EtOH (3 ml)
15. additionL-tartaric acid (27 mg) was added
16. stirringby stirring at room temperature overnight
17. filtrationThe precipitated solid was collected by filtration