Diisopropylethylamine → 3-[4-(4-Chloro-phenyl)-piperazin-1-yl]-2-methyl-1-[4-(4-nitro-3-trifluoromethyl-phenylamino)-piperidin-1-yl]-propan-1-one

3-[4-(4-Chloro-phenyl)-piperazin-1-yl]-2-methyl-propionic acid lithium salt (62 mg; 0.22 mmol, prepared in accordance with Example 60), diisopropylethyl amine (87 μL; 0.50 mmol) and tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (76 mg; 0.20 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-nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine hydrochloride (63 mg; 0.20 mmol, prepared in accordance with Example 8) in dimethylformamide (0.5 mL) 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 (47 mg; 0.08 mmol). The structure was confirmed using Protocol I-A. Calculated mass=554; observed mass=554; HPLC retention time=3.45 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 record

ord-0b5da39c048c4866a88bfac98981fa8c

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096524B2