反应详情

温度

100 °C

To a DMF solution (2.0 ml) of 4-{2-[bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid (3-bromo-phenyl)-methyl-amide (70.5 mg) obtained in Step B, tris(dibenzylideneacetone) dipalladium (4.3 mg), S-Phos (3.8 mg) and potassium phosphate (39.8 mg), 2-piperazin-1-yl-ethanol (23 μl) was added, and degassed under ultrasonic irradiation. After this was stirred at 100° C. for 4 hours, water (10 ml) was added, followed by extraction with ethyl acetate (10 ml×2), and the organic layer was dried over sodium sulfate. After the sodium sulfate was filtered off, the solvent was distilled off under reduced pressure, followed by purification by silica gel column chromatography, to obtain 4-{2-[bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {3-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-phenyl}-methyl-amide. The PMB groups were removed according to Deprotection method 3, to obtain the desired compound (D-153) as a colorless solid (7.2 mg, 14%).

1. customdegassed under ultrasonic irradiation
2. additionwater (10 ml) was added
3. extractionfollowed by extraction with ethyl acetate (10 ml×2)
4. dry with materialthe organic layer was dried over sodium sulfate
5. filtrationAfter the sodium sulfate was filtered off
6. distillationthe solvent was distilled off under reduced pressure
7. customfollowed by purification by silica gel column chromatography