反应详情

温度

100 °C

A mixture of (±)-methanesulfonic acid (2-{3-[8-(3-cyano-phenyl)-6-(4-methoxy-phenyl)-5-methyl-7-oxo-5,6,7,8-tetrahydro-pyrimido[4,5-d]pyrimidin-2-ylamino]-phenyl}-ethyl)-ester (0.19 g; 0.32 mmol) (from Example 5a supra) and dimethylamine (2.0 M in tetrahydrofuran; 2.00 mL; 4.00 mmol) (Aldrich) in a bomb bottle and heated at 100° C. overnight. Upon cooling, the mixture was concentrated and the residue was partitioned between ethyl acetate and water. The organic phase was washed with water and brine, dried over anhydrous sodium sulfate and concentrated. At this point, the crude material was combined with material from an earlier run and purified by flash chromatography (Biotage, 12S; 100:0 to 50:50 ethyl acetate-methanol). This material was then crystallized from ethyl acetate and ether to give (±)-3-[7-[3-(2-dimethylamino-ethyl)-phenylamino]-3-(4-methoxy-phenyl)-4-methyl-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl]-benzonitrile as a solid. (Yield 0.12 g; 26.8%).

1. temperatureUpon cooling
2. concentrationthe mixture was concentrated
3. customthe residue was partitioned between ethyl acetate and water
4. washThe organic phase was washed with water and brine
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated
7. custompurified by flash chromatography (Biotage, 12S; 100:0 to 50:50 ethyl acetate-methanol)
8. customThis material was then crystallized from ethyl acetate and ether