Triethylamine → 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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence