反应详情

To a solution of 2-[(cyclopentylmethyl)(ethyl)amino]-5-(trifluoromethyl)benzaldehyde (3.34 g, 11.2 mmol) obtained in Step 3 and 5-[2-(methylthio)ethoxy]pyrimidin-2-amine (2.27 g, 12.3 mmol) obtained in Step 1 in toluene (80 mL) was added acetic acid (317 mg, 5.19 mmol), and the mixture was refluxed by heating for 4 hours with a Dean-Stark apparatus. The reaction mixture was left to cool to room temperature, and then added with sodium triacetoxyborohydride (4.73 g, 22.3 mmol) on an ice bath with stirring, and the mixture was stirred at room temperature for 60 hours. The reaction mixture was added with water, and extracted with chloroform, and then the organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=20:1→10:1→4:1) to obtain N-({2-[(cyclopentylmethyl)(ethyl)amino]-5-(trifluoromethyl)phenyl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine (4.39 g, 84%) as a pale yellow oil.

1. temperaturethe mixture was refluxed
2. temperatureby heating for 4 hours with a Dean-Stark apparatus
3. waitThe reaction mixture was left
4. stirringthe mixture was stirred at room temperature for 60 hours
5. extractionextracted with chloroform
6. washthe organic layer was washed with water and saturated brine
7. dry with materialdried over anhydrous sodium sulfate
8. concentrationconcentrated under reduced pressure
9. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=20:1→10:1→4:1)