反应详情

温度

80 °C

To a mixture of tert-butyl (2S,5S)-2-methyl-5-[4-[4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]phenyl]-1H-imidazol-2-yl]pyrrolidine-1-carboxylate (180 mg, 0.34 mmol), methyl N-[(1S)-1-[(2S,5S)-2-(5-iodo-1H-benzimidazol-2-yl)-5-methyl-pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamate (164.7 mg, 0.34 mmol), Pd(dppf)(Cl)2.CH2Cl2 (27.77 mg, 0.034 mmol) in 2-propanol (2 ml) is added aq NaHCO3 (1.7 mL of 1 M, 1.7 mmol). The reaction mixture is purged with N2, heated at 80° C. overnight, diluted with EtOAc, washed with H2O and brine. The organic phase is dried over Na2SO4, filtered and concentrated. The residue is purified by flash column chromatography on silica gel (1 to 30% MeOH in CH2Cl2) to afford the tert-butyl (2S,5S)-2-[4-[4-[4-[2-[(2S,5S)-1-[2-(methoxycarbonylamino)-3-methyl-butanoyl]-5-methyl-pyrrolidin-2-yl]-1H-benzimidazol-5-yl]phenyl]phenyl]-1H-imidazol-2-yl]-5-methyl-pyrrolidine-1-carboxylate (97 mg, 37.5%) as a beige solid.

1. customThe reaction mixture is purged with N2
2. additiondiluted with EtOAc
3. washwashed with H2O and brine
4. dry with materialThe organic phase is dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue is purified by flash column chromatography on silica gel (1 to 30% MeOH in CH2Cl2)