1-Hydroxybenzotriazole → 5-Phenyl-isoxazole-3-carboxylic acid (2-{4-[(2-bromo-phenyl)-methyl-amino]-piperidin-1-yl}-2-oxo-ethyl)-amide

Participants

Reaction Steps

To a stirred solution of [(5-phenyl-isoxazole-3-carbonyl)-amino]-acetic acid (62.9 mg, 0.00025 mol) in DMF (2 mL) was added DIPEA (0.159 g, 0.00123 mol), HOBt (41.4 mg, 0.00031 mol) and EDCI.HCl (58.8 mg, 0.0003° mol) at ambient temperature. After 2 minutes (2-bromo-phenyl)-methyl-piperidin-4-yl-amine hydrochloride (0.068 g, 0.00025 mol) was added and the resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water and the resulting precipitate was isolated by filtration. Purification by column chromatography using basic aluminium oxide (50-100% ethyl acetate in hexane) afforded 0.039 g (35%) of 5-phenyl-isoxazole-3-carboxylic acid (2-{4-[(2-bromo-phenyl)-methyl-amino]-piperidin-1-yl}-2-oxo-ethyl)-amide. LCMS: 497.11 (M+1)+, 97.87%, 1H NMR (DMSO-d6): δ 8.58 (t, 1H), 7.93 (m, 2H), 7.52 (m, 4H), 7.4 (s, 1H), 7.15 (m, 2H), 6.9 (m, 1H), 4.3 (d, 1H), 4.15 (t, 2H), 3.8 (d, 1H), 3.0 (m, 1H), 2.65 (m, 1H), 2.55 (s, 3H), 1.75 (m, 3H), 1.5 (m, 2H).

Provenance & Evidence