1-Hydroxybenzotriazole → 3-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-3-oxo-N-(6-phenyl-pyridin-3-yl)-propionamide

Participants

Reaction Steps

To a stirred solution of 3-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-3-oxo-propionic acid (0.1 g, 0.00032 mole) in DMF (5 mL) was added DMAP (0.059 g, 0.00048 mole), HOBt (0.051 g, 0.00038 mole) and EDCI.HCl (0.073 g, 0.00038 mole). After 2 minutes 6-phenyl-pyridin-3-ylamine (0.06 g, 0.00035 mole) was added and the resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water and the product was extracted with ethyl acetate. The organic layers were dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography using silica gel 60-120 mesh (50% ethyl acetate in hexane) to afford 0.026 g (19%) of 3-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-3-oxo-N-(6-phenyl-pyridin-3-yl)-propionamide. LC-MS purity: 468 (M+1)+, 93.7%, 1H NMR (CDCl3): δ 10.5 (s, 1H), 8.8 (s, 1H), 8.3 (d, 1H), 8.0 (d, 2H), 7.7 (d, 1H), 7.4 (m, 4H), 6.7 (m, 2H), 4.7 (m, 1H), 4.2 (m, 1H), 3.8 (m, 1H), 3.7 (m, 2H), 3.55 (s, 2H), 2.0 (m, 4H).

Provenance & Evidence