反应详情

温度

90 °C

A solution of 4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-fluorophenyl trifluoromethanesulfonate (Intermediate 6-4; 302 mg, 0.77 mmol) and methyl 2-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetate (Intermediate 6-2; 226 mg, 0.77 mmol) and potassium phosphate, tri-basic (196 mg, 0.92 mmol) in DME (10 mL), methanol (5 mL) and water (2.5 mL) was thoughroughly degassed. The mixture was treated with PdCl2(dppf)-DCM adduct (31.4 mg, 0.04 mmol), degassed again and the atmosphere replaced with nitrogen before being heated to 90° C. for 4 hours. The reaction mixture was allowed to cool to room temperature and then evaporated. The crude product was partitioned between EtOAc (75 mL), and saturated brine (75 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 70% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,2′-difluorobiphenyl-4-yl)acetate (240 mg, 76%) as a cream solid.

1. customdegassed again
2. temperatureto cool to room temperature
3. customevaporated
4. customThe crude product was partitioned between EtOAc (75 mL), and saturated brine (75 mL)
5. dry with materialThe organic layer was dried over MgSO4
6. filtrationfiltered
7. customevaporated
8. customto afford crude product
9. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 70% EtOAc in isohexane
10. customPure fractions were evaporated to dryness