反应详情

To a suspension of methyl N-[(1S)-1-[(2S,4S)-2-(5-iodo-1H-benzimidazol-2-yl)-4-methyl-pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamate (52.40 mg, 0.1082 mmol), methyl ((S)-1-((2S,4S)-2-(4-iodo-1H-imidazol-2-yl)-4-methylpyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamate (47 mg, 0.1082 mmol), [1,1′-biphenyl]-4,4′-diyldiboronic acid (26.17 mg, 0.1082 mmol), Pd(DPPF)(Cl)2.CH2Cl2 (4.418 mg, 0.005410 mmol) and 1 mL of 2-propanol in a microwave vial is added 1M aqueous NaHCO3 (541.0 μL, 0.5410 mmol). The reaction mixture is stirred for 3 minutes at room temperature and is heated to 150° C. in the microwave for 10 minutes. The reaction mixture is concentrated to dryness. The residue is purified by flash column chromatography on silica gel (0 to 10% methanol in CH2Cl2) and is further purified by reverse phase preparative HPLC to give ((S)-1-{(2S,4S)-2-[5-(4′-{2-[(2S,4S)-1-((S)-2-methoxycarbonylamino-3-methyl-butyryl)-4-methyl-pyrrolidin-2-yl]-1H-imidazol-4-yl}-biphenyl-4-yl)-1H-benzoimidazol-2-yl]-4-methyl-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (12 mg, 25%).

1. temperatureis heated to 150° C. in the microwave for 10 minutes
2. concentrationThe reaction mixture is concentrated to dryness
3. customThe residue is purified by flash column chromatography on silica gel (0 to 10% methanol in CH2Cl2)
4. customis further purified by reverse phase preparative HPLC