反应详情

温度

100 °C

To a mixture of 1-methyl-5-(2-chloro-ethoxy)-2-methyl-1H-indole-3-carboxylic acid benzyl ester (0.576 mmol, 0.206 g, Example 8, Step A) in 5.76 mL of DMF was added potassium carbonate (0.576 mmol, 0.080 g), potassium iodide (0.0576 mmol, 0.010 g), and diethylamine (2.30 mmol, 0.238 mL, Aldrich). The mixture was heated at 100° C. for 20 hours, an additional 2.30 mmol of diethylamine was added and heating was continued for 21 hours. The solution was cooled to room temperature, diluted with water (10 mL), and extracted with ethyl acetate (4×15 mL). The combined extracts were washed with water (10 mL), saturated aqueous NaCl (10 mL), dried over MgSO4, and concentrated to a brown oil (0.234 g). The product was purified by silica gel flash column chromatography (5-10% MeOH/CH2Cl2) to give a tan solid (0.114 g, 50/o): mp 73-74° C.; IR (KBr) 2968, 2918, 1692, 1186, 1101 cm−1; 1HNMR (400 MHz, DMSO-d6) δ 0.92 (t, J=7.08 Hz, 6H, N(CH2CH3)2), 2.46-2.51 (m, 4H, 2 NCH2), 2.66 (s, 3H, ArCH3), 2.68-2.73 (m, 2H, NCH2), 3.65 (s, 3H, NCH3), 3.85 (t, J=6.11 Hz, 2H, CH2OAr), 5.28 (s, 2H, CO2CH2Ph), 6.75 (dd, J=8.79, 2.44 Hz, 1H, ArH), 7.28-7.32 (m, 1H, ArH), 7.35-7.39 (m, 4H, ArH), 7.46 (d, J=7.57 Hz, 2H, ArH); MS(APCI+): m/z 395.1 (M+1). HPLC (ALLTECH/ALLTIMA C-18,50:50-2:98H2O/CH3CN+0.05% TFA): retention time=3.617 min, 96.84% purity.

1. temperatureheating
2. temperatureThe solution was cooled to room temperature
3. extractionextracted with ethyl acetate (4×15 mL)
4. washThe combined extracts were washed with water (10 mL), saturated aqueous NaCl (10 mL)
5. dry with materialdried over MgSO4
6. concentrationconcentrated to a brown oil (0.234 g)
7. customThe product was purified by silica gel flash column chromatography (5-10% MeOH/CH2Cl2)
8. customto give a tan solid (0.114 g, 50/o)