N,N-二异丙基乙胺 → 3-(1-{4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyryl}-piperidin-4-ylamino)-benzonitrile

4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyric acid lithium salt (120 mg; 0.37 mmol, prepared in accordance with Example 3), diisopropylethyl amine (150 μL; 0.85 mmol) and tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (129 mg; 0.34 mmol) are diluted in a 2 to 1 mixture of dimethylformamide and tetrahydrofuran (2.5 mL) and the resulting solution is stirred for 5 minutes. A solution 3-(piperidin-4-ylamino)-benzonitrile hydrochloride (80 mg; 0.34 mmol, prepared in accordance with Example 6) in dimethylformamide (850 μL) is added and the reaction is then stirred for 60 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 (67 mg; 0.14 mmol). The structure was confirmed using Protocol I-B. Calculated mass=500; observed mass=500; HPLC retention time=4.40 min.

1. stirringthe reaction is then stirred for 60 minutes 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记录

ord-d3e612ee0c6742c0a8a6bd44c92edbbc

来源数据集

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

专利号

US09096524B2