反应详情

DIPEA (0.407 g, 0.545 mL, 3.15 mmol) was added to a stirred solution of [2-(4-Hydroxy-phenyl)-acetyl amino]-acetic acid (55 mg, 0.26 mmol) in DMF (5 mL). HOBT (39 mg, 2.8 mmol) and EDCI.HCl (110 mg, 0.57 mmol) were added at room temperature. After 2 minutes, piperazine-1-yl-(2-trifluoromethyl-phenyl)-methanone hydrochloride (85.2 mg, 0.29 mmol) was added. The resulting mixture was stirred at room temperature overnight. 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-XDB-9.4×250 mm, 5 μm, mobile phase: A, 0.1% Trifluoroacetic acid, B-Acetonitrile, Flow: 7 ml/min) afforded 68 mg (45% yield) of 2-(4-hydroxy-phenyl) N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-acetamide as a white crystalline solid. LC-MS purity: 94.32%, HPLC purity: 98.38%. 1H NMR (DMSO): δ 9.4 (s, 1H,), 8.0 (t, 1H), 7.9-7.7 (m, 2H), 7.65 (t, 1H), 7.5 (d, 1H), 7.0 (d, 2H), 6.6 (d, 2H), 4.04-3.9 (d, 2H), 3.7-3.5 (m, 4H), 3.25 (m, 4H), 3.0 (m, 2H).

1. extractionthe product was extracted with EtOAc
2. washThe organic layer was washed with brine
3. dry with materialdried over Na2SO4
4. concentrationconcentrated under reduced pressure
5. customto afford the crude product
6. customPurification by preparative HPLC (Column