反应详情

A solution of 3,5-dimethyl-6-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazine-2-carboxamide (353 mg, 1 mmol), methyl 2-(3-fluoro-4-(trifluoromethylsulfonyloxy)phenyl)acetate (Intermediate 25-2; 411 mg, 1.30 mmol) and tripotassium phosphate (318 mg, 1.50 mmol) in DME (6 mL), ethanol (3.00 mL) and water (1.500 mL) was put under vacuum and refilled with nitrogen before addition of (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (DCM adduct) (65.8 mg, 0.08 mmol). The reaction mixture was heated to and left to stir overnight for 16 hrs. The reaction mixture was allowed to cool to room temperature and then evaporated. The residue was partitioned between water (20 mL) and EtOAc (50 mL). The aqueous was re-extracted with EtOAc (2×10 mL) and the combined organics washed with brine (20 mL), dried (MgSO4) and evaporated to give crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane on 40 g silicycle column. Pure fractions were evaporated to dryness to afford methyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-fluorobiphenyl-4-yl)acetate (180 mg, 45.8%) as a white solid.

1. temperatureThe reaction mixture was heated to and
2. waitleft
3. customevaporated
4. customThe residue was partitioned between water (20 mL) and EtOAc (50 mL)
5. extractionThe aqueous was re-extracted with EtOAc (2×10 mL)
6. washthe combined organics washed with brine (20 mL)
7. dry with materialdried (MgSO4)
8. customevaporated
9. customto give crude product
10. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane on 40 g silicycle column
11. customPure fractions were evaporated to dryness