Diisopropylethylamine → 4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-1-[4-(5-trifluoromethyl-pyridin-2-ylamino)-piperidin-1-yl]-butan-1-one

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Reaction Steps

4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyric acid lithium salt (16 mg; 0.05 mmol, prepared in accordance with Example 3), diisopropylethyl amine (18 μL; 0.10 mmol) and tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (19 mg; 0.05 mmol, prepared in accordance with Example 50) 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 piperidin-4-yl-(5-trifluoromethyl-pyridin-2-yl)-amine hydrochloride (14 mg; 0.05 mmol) in dimethylformamide (0.5 mL) is added and the reaction is then stirred for 150 minutes 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 (14 mg; 0.03 mmol). The structure was confirmed using Protocol I-B. Calculated mass=544; observed mass=544; HPLC retention time=4.47 min.

Provenance & Evidence