反应详情

To a solution of tert-butyl (2S,4S)-2-(5-iodo-1H-benzimidazol-2-yl)-4-methyl-pyrrolidine-1-carboxylate (68.5 mg, 0.16 mmol) in DMF (3 mL) are sequentially added tert-butyl (2S,4S)-2-[4-(4-ethynylphenyl)-1H-imidazol-2-yl]-4-methyl-pyrrolidine-1-carboxylate (47 mg, 0.13 mmol), Pd(DPPF)(Cl)2.CH2Cl2 (5.4 mg, 0.0067 mmol). The mixture is degassed well under vacuum and to it is added TEA (37 uL, 0.27 mmol), followed by CuI (1.2 mg, 0.0067 mmol). Then the reaction mixture is stirred under nitrogen at rt overnight. After removal of the solvent, the crude is purified by flash column chromatography on silica gel using methanol/CH2Cl2 0-5% to obtain tert-butyl (2S,4S)-2-[4-[4-[2-[2-[(2S,4S)-1-tert-butoxycarbonyl-4-methyl-pyrrolidin-2-yl]-1H-benzimidazol-5-yl]ethynyl]phenyl]-1H-imidazol-2-yl]-4-methyl-pyrrolidine-1-carboxylate (56 mg, 64%).

1. customThe mixture is degassed well under vacuum and to it
2. customAfter removal of the solvent
3. customthe crude is purified by flash column chromatography on silica gel