Diisopropylethylamine → 4-(1-{2-Methyl-3-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-propionyl}-piperidin-4-ylamino)-2-trifluoromethyl-benzonitrile

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Reaction Steps

2-Methyl-3-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-propionic acid (57 mg; 0.18 mmol, prepared in accordance with Example 67), diisopropylethyl amine (140 μL; 0.8 mmol) and tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (65 mg; 0.17 mmol) are diluted in a 2 to 1 mixture of dimethylformamide and tetrahydrofuran (1.5 mL) and the resulting solution is stirred for 5 minutes. A solution of 4-(Piperidin-4-ylamino)-2-trifluoromethyl-benzonitrile (50 mg; 0.17 mmol) in dimethylformamide (0.5 mL) is added and the reaction is then stirred for 1 hour at room temperature. Following dilution with dichloromethane (10 mL), the organic layer is sequentially washed with water (5 mL), aq. sat. sodium hydrogen carbonate (3×5 mL), is dried over magnesium sulfate and concentrated under reduced pressure. Upon addition of acetonitrile to the residue obtained a precipitation is observed. The precipitate is filtered, washed with acetonitrile (2×3 mL) and dried under high vacuum to afford the desired product (98 mg; 0.17 mmol). The structure was confirmed using Protocol II-B. Calculated mass=568; observed mass=568; HPLC retention time=4.812 min.

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