反应详情

温度

160 °C

1-(3-Chloro-4-methoxyphenyl)-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amine (190 mg, 0.43 mmol), zinc cyanide (0.024 mL, 0.38 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (52.6 mg, 0.13 mmol), tris(dibenzylideneacetone)dipalladium(0) (58.7 mg, 0.06 mmol), DMF (5 mL) and a drop of water were added into a vial and heated in a microwave reactor for 1 h at 160° C. The mixture was filtered, diluted with MeOH and purified by preparative HPLC. The fractions containing the desired product were pooled and the MeCN removed in vacuo. The resulting aqueous residue was diluted with saturated aqueous NaHCO3 and extracted with DCM. The combined organics were passed through a phase separator (Sorbent), concentrated and dried in vacuum oven at 40° C. over night, to afford 85 mg (45%) of the title compound.

1. filtrationThe mixture was filtered
2. additiondiluted with MeOH
3. custompurified by preparative HPLC
4. additionThe fractions containing the desired product
5. customthe MeCN removed in vacuo
6. additionThe resulting aqueous residue was diluted with saturated aqueous NaHCO3
7. extractionextracted with DCM
8. concentrationconcentrated
9. customdried in vacuum oven at 40° C. over night