N-methyl-2-pyrrolidone → 5-{8-[(3S)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl}pyrimidin-2-amine

Temperatur

100 °C

An N-methyl-2-pyrrolidone suspension (10 ml) of 5-[8-chloro-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amine (1.02 g, 2.46 mmol) and (2S)-2-methylpiperazine (1.23 g, 12.3 mmol) was heated at 120° C. to dissolve and then the resulting mixture was stirred at 100° C. for 5 hours. The resulting mixture was left standing to cool, poured into methylene chloride-methanol (10:1), and 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 solid was washed with a small amount of methylene chloride and collected by filtration to give the title compound (362.9 mg). The filtrate was concentrated under reduced pressure and the resulting residue was purified by medium pressure silica gel column chromatography (methylene chloride:methanol=32:1 to 7:1) to give the title compound (623.8 mg). These lots were combined to give the title compound (986.7 mg, 84%) as a pale yellow solid.

1. dissolutionto dissolve
2. waitThe resulting mixture was left
3. temperatureto cool
4. washwashed with saturated aqueous sodium hydrogen carbonate solution
5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
6. filtrationthe mixture was filtrated
7. concentrationthe filtrate was concentrated under reduced pressure
8. washthe resulting solid was washed with a small amount of methylene chloride
9. filtrationcollected by filtration

ORD-Eintrag

ord-ea081eb3beea4b7e8ece94bc353e8636

Quelldatensatz

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08097622B2