反应详情

温度

140 °C

A mixture of 2-{2-[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidin-1-yl]ethoxy}ethyl benzoate (328 mg), 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline (264 mg), pyridine hydrochloride (159 mg) and 1-methyl-2-pyrrolidone (7.5 mL) was stirred at 140° C. for 33.5 hrs. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate (15 mL), and extracted with ethyl acetate (35 mL×2). The organic layers were combined and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→0:100). The object fraction was concentrated under reduced pressure and the residue was dissolved in methanol (5 mL). 1N Aqueous sodium hydroxide solution (1 mL) was added and the mixture was stirred at room temperature for 2 hrs. After concentration of the reaction mixture under reduced pressure, water (30 mL) was added, and the mixture was extracted with ethyl acetate (40 mL×2). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→0:100) and recrystallized from ethyl acetate-hexane to give the title compound (50 mg).

1. extractionextracted with ethyl acetate (35 mL×2)
2. dry with materialdried over anhydrous magnesium sulfate
3. concentrationAfter concentration under reduced pressure
4. concentrationThe object fraction was concentrated under reduced pressure
5. dissolutionthe residue was dissolved in methanol (5 mL)
6. addition1N Aqueous sodium hydroxide solution (1 mL) was added
7. stirringthe mixture was stirred at room temperature for 2 hrs
8. additionAfter concentration of the reaction mixture under reduced pressure, water (30 mL) was added
9. extractionthe mixture was extracted with ethyl acetate (40 mL×2)
10. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
11. concentrationconcentrated under reduced pressure
12. customThe residue was purified by silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→0:100)
13. customrecrystallized from ethyl acetate-hexane