Methanol → Methyl 2-(4'-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)propanoate

Participants

Reaction Conditions

Reaction Steps

A solution of 4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)phenyl trifluoromethanesulfonate (Intermediate 7-4; 1.249 g, 3.33 mmol) and methyl 2-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoate (Intermediate 8-2; 1.08 g, 3.33 mmol) and potassium phosphate, tri-basic (0.847 g, 3.99 mmol) in DME (16 mL), methanol (8.00 mL) and water (4.00 mL) was thoughroughly degassed. The mixture was treated with PdCl2(dppf)-DCM adduct (0.136 g, 0.17 mmol), degassed again and the atmosphere replaced with nitrogen before being heated to 90° C. for 4 hours in the microwave. 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-chlorobiphenyl-4-yl)propanoate (0.841 g, 59.6%) as a beige solid.

Provenance & Evidence