反应详情

温度

130 °C

3 chloro-4-(piperazin-1-yl)benzoic acid hydrochloride (142 mg) was suspended in DMF (3 ml), and tert-butyl (2-{[3-(2-chloropyrimidin-5-yl)benzyl](methyl)amino}-2-oxoethyl)carbamate (190 mg) and DIPEA (371 mg) were added thereto, followed by stirring at 130° C. 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 dioxane, and 4 M hydrogen chloride/dioxane (1 ml) was added thereto, followed by stirring at room temperature overnight. The precipitated solid was collected by filtration to obtain 3-chloro-4-{4-[5-(3-{[glycyl(methyl)amino)methyl}phenyl)pyrimidin-2-yl]piperazin-1-yl}benzoic acid dihydrochloride (72 mg).

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