反应详情

温度

70 °C

To a suspension of 7-amino-4-(4-isopropyl-piperazin-1-yl)-2-methyl-2,3-dihydro-isoindol-1-one (1.62 g, 5.6 mmol) and potassium carbonate (2.55 g, 8.7 mmol) in dimethylsulfoxide (30 mL), 2, 4, 5-trichloropyrimidine (970 μL, 8.4 mmol) is added and stirred at 70° C. for 4 hours. To the mixture is added 2,4,5-trichloropyrimidine (650 μL, 5.6 mmol) and the mixture is stirred at 70° C. for 6 hours. The mixture is cooled and then extracted twice with dichloromethane. The organic layer is successively washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue is purified by silica gel column chromatography to afford 7-(2,5-dichloro-pyrimidin-4-ylamino)-4-(4-isopropyl-piperazin-1-yl)-2-methyl-2,3-dihydro-isoindol-1-one (1.95 g) as yellow solids in 80% yield. Rf=0.26 (MeOH/AcOEt=1/4). 1H-NMR (400 MHz, CDCl3, δ, ppm): 1.13 (s, 3H), 1.14 (s, 3H), 2.87-2.69 (m, 5H), 3.18-3.08 (m, 4H), 3.22 (s, 3H), 4.40 (s, 2H), 7.20 (d, 1H), 8.20 (s, 1H), 8.66 (d, 1H), 11.0 (s, 1H).

1. additionis added
2. stirringthe mixture is stirred at 70° C. for 6 hours
3. temperatureThe mixture is cooled
4. extractionextracted twice with dichloromethane
5. washThe organic layer is successively washed with water and brine
6. dry with materialdried over magnesium sulfate
7. customevaporated in vacuo
8. customThe residue is purified by silica gel column chromatography