反应详情

2-(4-Aminophenyl)-1-cyclobutyl-6-ethoxy-1H-indole-3-carbonitrile (40 mg, 0.12 mmol), prepared as in example 1CM, step B, is combined with 4-nitrophenyl chloroformate (60 mg, 0.30 mmol), DCE (0.4 mL), and pyridine (25 μL, 0.31 mmol). This suspension is stirred at room temperature for 1 h. 2-(2-methoxyethoxy)ethanol (150 μL, 1.25 mmol) is added. This mixture is heated at 75° C. overnight. The reaction mixture is then diluted in CH2Cl2 and is washed with dilute aqueous NaOH to remove the yellow nitrophenol by-product. The organic layer is dried and concentrated. Purification by silica gel chromatography (CH2Cl2/EtOAc, 4/1), followed by trituration with hexanes/acetone (2/1) yields 1-cyclobutyl-6-ethoxy-2-[4-(2-pyridin-2-yl-ethylamino)-phenyl]-1H-indole-3-carbonitrile (23 mg, 42%) as a white solid.

1. temperatureThis mixture is heated at 75° C. overnight
2. washis washed with dilute aqueous NaOH
3. customto remove the yellow nitrophenol by-product
4. customThe organic layer is dried
5. concentrationconcentrated
6. customPurification by silica gel chromatography (CH2Cl2/EtOAc, 4/1)