反应详情

温度

150 °C

A solution of 4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)phenylboronic acid (243 mg, 0.90 mmol), methyl 2-(3,5-difluoro-4-(trifluoromethylsulfonyloxy)phenyl)acetate (Intermediate 24-2; 300 mg, 0.90 mmol) and tripotassium phosphate (286 mg, 1.35 mmol) in butyronitrile (2 mL) was put under vacuum and refilled with nitrogen before addition of (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (DCM adduct) (59.1 mg, 0.07 mmol). The reaction mixture was heated in the microwave at 150° C. for 6 hours. The reaction mixture was concentrated and diluted with DCM (25 mL), and washed with water (2×25 mL). The organic layer was dried by passing through a phase seperating cartridge and evaporated to afford crude product. The crude product was purified by flash Silica chromatography {CombiFlash Companion—Presearch Ltd}, column size=12 g, flow rate=30 mL/min, 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)-2,6-difluorobiphenyl-4-yl)acetate (96 mg, 26.0%) as a slightly coloured (purple tinge) solid.

1. concentrationThe reaction mixture was concentrated
2. additiondiluted with DCM (25 mL)
3. washwashed with water (2×25 mL)
4. customThe organic layer was dried
5. customseperating cartridge
6. customevaporated
7. customto afford crude product
8. customThe crude product was purified by flash Silica chromatography {CombiFlash Companion—Presearch Ltd}, column size=12 g, flow rate=30 mL/min, elution gradient 0 to 50% EtOAc in isohexane
9. customPure fractions were evaporated to dryness