反应详情

(±)-3-(3-(4-Methoxy-phenyl)-4-methyl-7-{3-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenylamino}-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl)-benzonitrile (0.25 g; 0.41 mmol) (from Example 7 supra) was dissolved in dimethyl sulfoxide (2.5 mL) and the resulting solution was cooled in an ice-water bath. Aqueous sodium hydroxide (1 M; 750 μL; 0.75 mmol) was added, resulting in the precipitation of the benzonitrile. Aqueous hydrogen peroxide (30%; 130 μL; 1.27 mmol) was then added. The cooling bath was removed. The solid went back into solution and a new solid precipitated out. After 3 hours the reaction mixture was diluted with water. The solid was collected, washed with water and air-dried under the house vacuum. Purification by flash chromatography (Biotage 12S; 90:10 to 60:40 chloroform-methanol gradient) and then crystallization from methanol-ethyl acetate gave (±)-3-(3-(4-methoxy-phenyl)-4-methyl-7-{3-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenylamino}-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl)-benzamide as a white solid. (Yield 35.7 mg; 14.3%). A second crop was collected by addition of ether to the mother liquor. (Yield 87.8 mg; 35.1%). Melting Point: 243–251° C. HR-MS(ES+) m/z Calculated for C34H38N8O3 ([M+H]+): 607.3140; Found: 607.3144.

1. temperaturethe resulting solution was cooled in an ice-water bath
2. customThe cooling bath was removed
3. customa new solid precipitated out
4. additionAfter 3 hours the reaction mixture was diluted with water
5. customThe solid was collected
6. washwashed with water
7. customair-dried under the house vacuum
8. customPurification by flash chromatography (Biotage 12S; 90:10 to 60:40 chloroform-methanol gradient)
9. customcrystallization from methanol-ethyl acetate