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

Triethylamine (55.8 μl, 0.40 mmol) was added to a methylene chloride suspension (3.0 ml) of 5-{8-[(3S)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl}pyrimidin-2-amine (87.1 mg, 0.18 mmol) at room temperature followed by the addition of acetoxyacetyl chloride (24.2 μl, 0.22 mmol) with ice cooling. The resulting mixture was stirred at room temperature for 90 minutes, then 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 (83.3 μl, 0.36 mmol) was added to a methanol-tetrahydrofuran (1:1) mixture solution (12.0 ml) of the resulting white solid, and the resulting mixture was stirred at room temperature for 25.5 hours. The reaction mixture was poured into methylene chloride and washed with saturated brine. 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 (85.0 mg, 87%) as a pale yellow solid.

1. washwashed with saturated aqueous sodium hydrogen carbonate solution
2. dry with materialdried over anhydrous sodium sulfate
3. filtrationAfter filtration
4. concentrationthe filtrate was concentrated under reduced pressure
5. stirringthe resulting mixture was stirred at room temperature for 25.5 hours
6. washwashed with saturated brine
7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
8. filtrationthe mixture was filtrated
9. concentrationthe filtrate was concentrated under reduced pressure
10. customthe resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1)

ORD-Eintrag

ord-2f27b90979b74b128beba0525dbe6d10

Quelldatensatz

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08309546B2