1-Hydroxybenzotriazole → 5-Phenyl-[1,3,4]oxadiazole-2-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide

DIPEA (106 mg, 0.142 mL, 0.82 mmol) followed by HOBT (40.8 mg, 0.30 mmol), EDCI.HCl (131.8 mg, 0.69 mmol) and 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone TFA salt (129 mg, 0.3 mmol) were added sequentially to a stirred solution of 5-phenyl-[1,3,4]oxadiazole-2-carboxylic acid lithium salt (52 mg, 0.27 mmol) in DMF (5 mL). The resulting mixture was maintained at room temperature for 6 hrs. Cold water was added and the product was extracted with ethyl acetate. The organic layer was washed with saturated brine solution, dried over sodium sulphate and concentrated. The crude residue was purified by column chromatography (using 60-120 mesh silica gel and 50% EtOAc in hexane as eluent) to afford 30 mg (22.4% yield) of 5-phenyl-[1,3,4]oxadiazole-2-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide as a white solid, LCMS purity: 87.99%, 1H NMR: (DMSO) δ 9.2 (t, 1H), 8.1 (d, 2H), 7.9-7.72 (dd, 2H), 7.72-7.6 (m, 3H), 7.6-7.5 (t, 1H), 4.3-4.1 (dd, 2H), 3.8-3.5 (m, 4H), 3.3-3.0 (m, 4H).

1. extractionthe product was extracted with ethyl acetate
2. washThe organic layer was washed with saturated brine solution
3. dry with materialdried over sodium sulphate
4. concentrationconcentrated
5. customThe crude residue was purified by column chromatography (using 60-120 mesh silica gel and 50% EtOAc in hexane as eluent)

ORD record

ord-ebeec8d430784e1a908ecf2e8124de65

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07842696B2