Diisopropylethylamine → 1-[4-(4-Methanesulfonyl-3-trifluoromethyl-phenylamino)-piperidin-1-yl]-4-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-butan-1-one

4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyric acid lithium salt (120 mg; 0.38 mmol, prepared in accordance with Example 3), diisopropylethyl amine (174 μL; 1.00 mmol) and tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (121 mg; 0.28 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 (4-methanesulfonyl-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine hydrochloride (103 mg; 0.32 mmol, prepared in accordance with Example 29) in dimethylformamide (0.5 mL) is added and the reaction is then stirred for 2 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 (36 mg; 0.06 mmol). The structure was confirmed using Protocol I-B. Calculated mass=621; observed mass=621; HPLC retention time=4.39 min.

1. stirringthe reaction is then stirred for 2 hours at room temperature
2. washthe organic layer is sequentially washed with water (5 mL), aq. sat. sodium hydrogen carbonate (5 mL)
3. dry with materialis dried over magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. customThe residue obtained
6. customis finally purified by preparative HPLC

ORD-Eintrag

ord-bb261b39d4f348b7817ea8877aa20792

Quelldatensatz

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09096524B2