反应详情

Triethylamine (63.1 μl, 0.45 mmol) was added to a methylene chloride solution (3.0 ml) of 5-[8-(3,3-dimethylpiperazin-1-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amine (101.3 mg, 0.21 mmol) at room temperature followed by the addition of acetoxyacetyl chloride (27.4 μl, 0.25 mmol) with ice cooling. The resulting mixture was stirred at room temperature for 1 hour followed by the addition of triethylamine (17.2 μl, 0.13 mmol) and acetoxyacetyl chloride (6.8 μl, 0.06 mmol) with ice cooling and the resulting mixture was further stirred at room temperature for 16 hours. The reaction mixture was poured into methylene chloride-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, a 25% by weight sodium methoxide-methanol solution (94.1 μl, 0.41 mmol) was added to a methanol-tetrahydrofuran (3:1) mixture solution (8.0 ml) of the resulting residue, and the resulting mixture was stirred at room temperature for 17 hours. The reaction mixture was poured into methylene chloride and washed with water and the organic layer was 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 (methylene chloride:methanol=10:1) to give the title compound (94.2 mg, 83%) as a pale yellow solid.

1. stirringthe resulting mixture was further stirred at room temperature for 16 hours
2. washwashed with saturated aqueous sodium hydrogen carbonate solution
3. dry with materialdried over anhydrous sodium sulfate
4. filtrationAfter filtration
5. concentrationthe filtrate was concentrated under reduced pressure
6. stirringthe resulting mixture was stirred at room temperature for 17 hours
7. washwashed with water
8. dry with materialthe organic layer was dried over anhydrous sodium sulfate
9. filtrationAfter filtration
10. concentrationthe filtrate was concentrated under reduced pressure
11. customthe resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1)