反应详情

温度

90 °C

A solution of 4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)phenyl trifluoromethanesulfonate (Intermediate 7-4; 289 mg, 0.77 mmol) and methyl 1-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclobutanecarboxylate (Intermediate 7-2; 270 mg, 0.77 mmol) and potassium phosphate, tri-basic (196 mg, 0.92 mmol) in DME (10 mL), MeOH (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, diluted with EtOAc (40 mL) and water (20 mL). This was passed through a silica pad washing with EtOAc. The filtrate was separated and washed with brine (20 mL) then 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 1-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)cyclobutanecarboxylate (239 mg, 69.0%) as a colourless gum.

1. customdegassed again
2. temperatureto cool
3. additiondiluted with EtOAc (40 mL) and water (20 mL)
4. washwashing with EtOAc
5. customThe filtrate was separated
6. washwashed with brine (20 mL)
7. customthen evaporated
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