Dimethylformamide → 3-(4-Hydroxy-phenyl) N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-propionamide

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Reaction Steps

DIPEA (145 mg, 0.194 mL, 1.12 mmol) was added to a stirred solution of [3-(4-hydroxy-phenyl)propionylamino]-acetic acid (50 mg, 0.22 mmol) in DMF (4 mL). HOBT (33.3 mg, 0.25 mmol) and EDCI.HCl (107 mg, 0.56 mmol) were added at room temperature. After 2 minutes piperazine-1-yl-(2-trifluoromethyl-phenyl)-methanone hydrochloride (72.6 mg, 0.25 mmol) was added. The resulting mixture was stirred at room temperature for 24 hours. Water was then added, and the product was extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure to afford the crude product. Purification by preparative HPLC (column: Zorbax-Eclipse-XDB-C18-9.4×250 mm, 5 μm, mobile phase: A-0.1% Trifluoroacetic acid, B-Acetonitrile, Flow: 7 ml/min) afforded 60 mg (58.25% yield) of 3-(4-Hydroxy-phenyl) N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-propionamide as a pale white crystalline solid (60 mg). LC-MS purity: 91.16%, HPLC purity: 98.8%. 1H NMR (DMSO): δ 9.2 (s, 1H,), 8.0 (t, 1H), 7.92-7.8 (m, 2H), 7.7 (t, 1H), 7.56 (d, 1H), 7.0 (d, 2H), 6.66 (d, 2H), 4.08-3.94 (d, 2H), 3.84-3.68 (m, 2H), 3.66-3.5 (bs, 4H), 3.2-3.1 (bd, 2H), 2.7 (bs, 2H), 2.4 (t, 2H).

Provenance & Evidence