反应详情

温度

150 °C

To a mixture of 2-chloro-4-(3-chloro-4-fluoro-phenyl)-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidine (200 mg, 0.43 mmol), 1-methyl-1H-imidazole (42 mg, 0.51 mmol), CuI (161 mg, 0.86 mmol), MgO (21 mg, 051 mmol), and PPh3 (22 mg, 0.086 mmol) in dioxane add Pd(OAc)2 (5 mg, mg, 0.021 mmol). Purge the reaction mixture for 10 minutes with dry N2. Heat the mixture at 150° C. for 24 hours, cool to room temperature, and partition between water and EtOAc. Dry the solution (Na2SO4), concentrate under reduced pressure. Purify the residue by flash column chromatography eluting with DCM:MeOH:NH4OH (95:5:1) to afford 4-(3-chloro-4-fluoro-phenyl)-2-(1-methyl-1H-imidazol-2-yl)-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidine. 1H NMR (2HCl salt, 300 MHz, DMSO-d6): δ3.35 (m, 4H); 4.01 (m, 4H); 4.31 (s, 3H, NCH3); 7.23 (m, 1H, Ar—H); 7.63 (m, 2H); 7.89 (s, 1H); 7.97 (s, 1H); 8.11 (m, 1H); 8.43 (m, 1H); 8.54 (m, 1H); 8.66 (m, 1H).

1. customPurge the reaction mixture for 10 minutes with dry N2
2. temperaturecool to room temperature
3. custompartition between water and EtOAc
4. dry with materialDry the solution (Na2SO4)
5. concentrationconcentrate under reduced pressure
6. customPurify the residue by flash column chromatography
7. washeluting with DCM:MeOH:NH4OH (95:5:1)