Sodium Hydroxide → 4-Isobutoxy-1H-indole-2-carboxylic acid [1-(2-hydroxy-ethyl)-piperidin-4-yl]-amide

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Reaction Conditions

Reaction Steps

4-Isobutoxy-1H-indole-2-carboxylic acid 80 (preparation see Example 8, 1 g, 4.29 mmol) is suspended in 5 ml of DMF, cooled to 0° C. and treated with Hünig's Base (1.46 ml, 8.58 mmol). The mixture is stirred for 15 min at 0° C. In a separate reaction flask, compound 192 (931 mg, 4.29 mmol) in 10 ml of DMF is cooled to 0° C., treated with 10M aqueous sodium hydroxide solution (0.858 ml, 8.58 mmol) and stirred for 15 min at this temperature. This solution is added to the above mentioned mixture, followed by benzotriazol-1-yl-oxytripyrrolidinphosphonium hexafluorophosphate (PyBOP, 2.34 g, 4.5 mmol) and stirred for 4 h at room temperature. The reaction mixture is diluted with ethyl acetate and washed with 2N sodium hydroxide solution, water and brine. Evaporation gave a semisolid, yellow crude product, which is treated with ether, filtered of and washed with ether.

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