Sodium Carbonate → Methyl 2-(4'-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,5-dichlorobiphenyl-4-yl)acetate

Participants

Reaction Conditions

Reaction Steps

A solution of 4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)phenylboronic acid (Intermediate 5-1; 312 mg, 1.15 mmol) and methyl 2-(2,5-dichloro-4-(trifluoromethylsulfonyloxy)phenyl)acetate (Intermediate 4-2; 375 mg, 1.02 mmol) and 2M sodium carbonate (0.830 mL, 1.66 mmol), tetrakis(triphenylphosphine)palladium(0) (73.2 mg, 0.06 mmol) and lithium chloride (76 mg, 1.79 mmol) in DME (10 mL) was degassed and then stirred at 85° C. for 17 hours. The reaction mixture was concentrated and diluted with EtOAc (75 mL), and washed sequentially with 2M HCl (25 mL) and saturated brine (25 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 50% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,5-dichlorobiphenyl-4-yl)acetate (148 mg, 32.6%) as a yellow solid.

Provenance & Evidence