反应详情

温度

50 °C

1-Hydroxybenzotriazole monohydrate (35.0 mg, 0.23 mmol), 1-(dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (65.7 mg, 0.34 mmol), and triethylamine (38.2 μl, 0.27 mmol) were added to an N,N-dimethylformamide suspension (2.0 ml) of 5-[9-(cyclopropylmethyl)-6-morpholin-4-yl-8-piperazin-1-yl-9H-purin-2-yl]pyrimidin-2-amine (99.7 mg, 0.23 mmol) and N,N-dimethylglycine hydrochloride (38.3 mg, 0.27 mmol) at room temperature. The resulting mixture was stirred for 20.5 hours and heated to 50° C. followed by the addition of triethylamine (38.2 μl, 0.27 mmol) and the resulting mixture was stirred for 6 hours. The resulting mixture was further stirred at room temperature for 17 hours and then the reaction mixture was poured into dichloromethane-methanol (10:1), washed with saturated aqueous sodium hydrogen carbonate solution, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the resulting residue was purified by preparative thin layer silica gel chromatography (dichloromethane:methanol=5:1) to give the title compound (84.6 mg, 71%) as a pale yellow solid.

1. stirringthe resulting mixture was stirred for 6 hours
2. stirringThe resulting mixture was further stirred at room temperature for 17 hours
3. washwashed with saturated aqueous sodium hydrogen carbonate solution
4. dry with materialdried over anhydrous sodium sulfate
5. filtrationAfter filtration
6. concentrationthe filtrate was concentrated under reduced pressure
7. customthe resulting residue was purified by preparative thin layer silica gel chromatography (dichloromethane:methanol=5:1)