反应详情

To a suspension of 5-(2-aminoethyl)-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidin-4-amine dihydrochloride (150 mg) and triethylamine (0.40 mL) in tetrahydrofuran (5.0 mL) was added 1-chlorocarbonyl-1-methylethyl acetate (0.12 mL) at room temperature. After stirring at room temperature for 3 days, aqueous sodium hydrogen carbonate was added, and the mixture was extracted with ethyl acetate. The organic layer washed with saturated brine, dried over magnesium sulfate and concentrated under reduced pressure. To a solution of the residue in ethanol (3.0 mL) was added 1N aqueous sodium hydroxide solution (1.5 mL) at room temperature. After stirring at room temperature for 24 hrs, the mixture was extracted with ethyl acetate. The organic layer washed with saturated brine, dried over magnesium sulfate and concentrated under reduced pressure, and the residue was separated and purified by basic silica gel column chromatography (eluent, ethyl acetate→ethyl acetate:methanol=9:1) to give the title compound (133 mg) as colorless crystals.

1. extractionthe mixture was extracted with ethyl acetate
2. washThe organic layer washed with saturated brine
3. dry with materialdried over magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. additionTo a solution of the residue in ethanol (3.0 mL) was added 1N aqueous sodium hydroxide solution (1.5 mL) at room temperature
6. stirringAfter stirring at room temperature for 24 hrs
7. extractionthe mixture was extracted with ethyl acetate
8. washThe organic layer washed with saturated brine
9. dry with materialdried over magnesium sulfate
10. concentrationconcentrated under reduced pressure
11. customthe residue was separated
12. custompurified by basic silica gel column chromatography (eluent, ethyl acetate→ethyl acetate:methanol=9:1)