Diisopropylethylamine → 3-[4-(4-Benzyloxy-phenyl)-piperazin-1-yl]-1-[4-(4-nitro-3-trifluoromethyl-phenylamino)-piperidin-1-yl]-propan-1-one

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Reaction Steps

3-[4-(4-Benzyloxy-phenyl)-piperazin-1-yl]-propionic acid lithium salt (134 mg; 0.39 mmol, prepared in accordance with Example 22), diisopropylethyl amine (174 μL; 0.35 mmol) and tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (133 mg; 0.35 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-nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine hydrochloride (114 mg; 0.35 mmol, prepared in accordance with Example 8) in dimethylformamide (0.5 mL) is added and the reaction is then stirred for 3 hours at room temperature. Following dilution with dichloromethane (10 mL), the organic layer is sequentially washed with water (5 mL), aq. sat. sodium hydrogen carbonate (5 mL), is dried over magnesium sulfate and concentrated under reduced pressure. The residue obtained is finally purified by preparative HPLC to deliver the desired product in pure form (61 mg; 0.10 mmol). The structure was confirmed using Protocol II-A. Calculated mass=612; observed mass=612; HPLC retention time=3.57 min.

Provenance & Evidence