反应详情

温度

60 °C

To a suspension of 4-(7-Amino-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (6.14 g, 18 mmol) and potassium carbonate (3.86 g, 4.76 mmol) in dimethylsulfoxide (60 mL), 2,4,5-trichloropyrimidine (3.1 mL, 27 mmol) is added and the mixture is stirred at 60° C. for 2 hours. To the mixture, 2,4,5-trichloro pyrimidine (1.0 mL, 9 mmol) is added. After stirring at 60° C. for 2 hours, 2,4,5-trichloropyrimidine (1.0 mL, 9 mmol) is added and the mixture is further allowed to stir at 60° C. for 10 hours. The mixture is cooled and then poured into iced water. The resulting brown solids are collected by filtration and washed with MeOH, and dried in vacuo at 50° C. to afford 4-[7-(2,5-Dichloro-pyrimidin-4-ylamino)-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl]-piperazine-1-carboxylic acid tert-butyl ester as brown solids (5.29 g) in 60% yield. Rf=0.28 (Hexane/AcOEt=111). 1H-NMR (400 MHz, CDCl3, δ, ppm): 1.50 (s, 9H), 2.99 (t, 4H), 3.23 (s, 3H), 3.59 (t, 4H), 4.40 (s, 2H), 7.18 (d, 1H), 8.21 (s, 1H), 8.67 (d, 1H), 11.0 (s, 1H).

1. additionis added
2. stirringAfter stirring at 60° C. for 2 hours
3. stirringto stir at 60° C. for 10 hours
4. temperatureThe mixture is cooled
5. filtrationThe resulting brown solids are collected by filtration
6. washwashed with MeOH
7. customdried in vacuo at 50° C.