反应详情

温度

80 °C

1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (51 mg, 0.06 mmol) was added to a degassed, ambient temperature solution of tert-butyl 2-[1-{[(benzyloxy)carbonyl]amino}-2-(4-bromophenyl)ethyl]-4-(2,2-dimethylbutyl)-1H-imidazole-1-carboxylate (367 mg, 0.63 mmol), sodium carbonate (200 mg, 1.9 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (244 mg, 1.2 mmol) in N,N-dimethylformamide/water (2:1) (30 mL). After stirring at 80° C. overnight, the reaction mixture was cooled, poured into water and extracted with diethyl ether. The combined organic extracts were dried (magnesium sulfate) and concentrated in vacuo. Pd (10 wt % on activated carbon) (catalytic) was added to a degassed, ambient temperature solution of the crude residue in methanol (5 mL). After stirring at ambient temperature under an atmosphere of hydrogen overnight, the reaction mixture was filtered through cotton and concentrated in vacuo. Triethylamine (0.61 mL, 4.4 mmol) followed by di-tert-butyl dicarbonate (687 mg, 3.1 mmol) were added to an ambient temperature solution of the crude residue in tetrahydrofuran (5 mL). After stirring at ambient temperature for 5 h, the reaction mixture was quenched with water and extracted with methylene chloride. The combined organic extracts were dried (magnesium sulfate) and concentrated in vacuo. Chromatography over silica eluting with 0-40% ethyl acetate/hexane afforded tert-butyl 4-(4-{2-[(tert-butoxycarbonyl)amino]-2-[1-(tert-butoxycarbonyl)-4-(2,2-dimethylbutyl)-1H-imidazol-2-yl]ethyl}phenyl)-1H-pyrazole-1-carboxylate.

1. temperaturethe reaction mixture was cooled
2. extractionextracted with diethyl ether
3. dry with materialThe combined organic extracts were dried (magnesium sulfate)
4. concentrationconcentrated in vacuo
5. additionPd (10 wt % on activated carbon) (catalytic) was added to a degassed, ambient temperature solution of the crude residue in methanol (5 mL)
6. stirringAfter stirring at ambient temperature under an atmosphere of hydrogen overnight
7. filtrationthe reaction mixture was filtered through cotton
8. concentrationconcentrated in vacuo
9. stirringAfter stirring at ambient temperature for 5 h
10. customthe reaction mixture was quenched with water
11. extractionextracted with methylene chloride
12. dry with materialThe combined organic extracts were dried (magnesium sulfate)
13. concentrationconcentrated in vacuo