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 (1.18 g; 2.02 mmol) (from Example 5a supra) and diethylamine (1.5 mL; 14.5 mmol) (Aldrich) in a pressure bottle and heated at 100° C. for 100 minutes. Upon cooling, the mixture was concentrated and the residue was partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated. Purification by flash chromatography (Biotage 40S; 100:0 to 50:50 ethyl acetate-methanol) followed by crystallization from ethyl acetate and hexanes gave (±)-3-[7-[3-(2-diethylamino-ethyl)-phenylamino]-3-(4-methoxy-phenyl)-4-methyl-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl]-benzonitrile. (Yield 0.66 g; 57.9%).

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 brine
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated
7. customPurification by flash chromatography (Biotage 40S; 100:0 to 50:50 ethyl acetate-methanol)
8. customfollowed by crystallization from ethyl acetate and hexanes