Triethylamine → 2-{4-[2-(2-Aminopyrimidin-5-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-8-yl]-cis-2,6-dimethylpiperazin-1-yl}-2-oxoethanol

Participants

Reaction Steps

Triethylamine (57.8 μl, 0.41 mmol) and acetoxyacetyl chloride (23.0 μl, 0.21 mmol) were added to a methylene chloride solution (3.0 ml) of 5-[8-(cis-3,5-dimethylpiperazin-1-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amine (92.9 mg, 0.19 mmol) with ice cooling. The resulting mixture was stirred at room temperature for 25 hours followed by the addition of triethylamine (15.8 μl, 0.11 mmol) and acetoxyacetyl chloride (6.3 μl, 0.06 mmol) and the resulting mixture was stirred for 17 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 (86.3 μl, 0.38 mmol) was added to a methanol (9.0 ml) suspension of the resulting residue, and the resulting mixture was stirred at room temperature for 5.5 hours. Tetrahydrofuran (3.0 ml) was added, the resulting mixture was stirred at 40° C. for 16.5 hours, then methanol was concentrated to a half amount under reduced pressure, the resulting mixture was poured into methylene chloride, and the resulting mixture was washed with saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over anhydrous sodium sulfate, the mixture was filtrated, 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 (82.6 mg, 80%) as a pale yellow solid.

Provenance & Evidence