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

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Reaction Conditions

Reaction Steps

HOBt (38 mg, 0.28 mmol) and DIPEA (145 mg, 1.12 mmol) were added to a stirred solution of 5-phenyl-isoxazole-3-carboxylic acid (43 mg, 0.22 mmol) in DMF (1.0 mL). Then reaction mass was cooled to 10° C. and EDCI.HCl (54 mg, 0.28 mmol) and 2-amino-1-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone (as TFA salt) (100 mg, 0.22 mmol) were added. Then resulting mixture was stirred at the room temperature overnight. The mixture was then diluted with water and the product extracted with ethyl acetate. The organic layer was washed with brine solution, dried over Na2SO4, evaporated and purified by column chromatography using silica gel (60-120 mesh) and 50% ethyl acetate in hexane as the eluant to afford 5-phenyl-isoxazole-3-carboxylic acid {2-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide as a solid in 49.1% yield. LC-MS purity: 95.66%, 1H NMR (DMSO-D6): δ 8.7 (t, 1H), 7.94 (m, 3H), 7.56 (m, 5H), 7.4 (s, 1H), 4.15 (m, 2H), 3.75 (m, 1H), 3.6 (m, 3H), 3.45 (m, 2H), 3.2 (m, 2H), 3.1 (m, 1H).

Provenance & Evidence