1-Hydroxybenzotriazole → N-biphenyl-4-yl-3-[4-(2-bromo-phenylamino)-piperidin-1-yl]-3-oxo-propionamide

Participants

Reaction Steps

To a stirred solution of N-biphenyl-4-yl-malonamic acid (0.071 g, 0.00028 mole) in DMF (2 mL) was added DIPEA (0.089 g, 0.0007 mole), HOBt (0.046 g, 0.00034 mole) and EDCI.HCl (0.065 g, 0.00034 mole). After 2 minutes (2-bromo-phenyl)-piperidin-4-yl-amine dihydrochloride (0.082 g, 0.00028 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 layer was washed with aqueous sodium bicarbonate solution, brine and concentrated. The resulting residue was purified by column chromatography using silica gel 60-120 mesh (70% ethyl acetate in hexane) to afford 0.025 g (17%) of N-biphenyl-4-yl-3-[4-(2-bromo-phenylamino)-piperidin-1-yl]-3-oxo-propionamide. LC-MS purity: 492 (M+1)+, 92.2%, 1H NMR (CDCl3): δ 10.0 (s, 1H), 7.66 (d, 2H), 7.58 (m, 4H), 7.44 (t, 3H), 7.34 (t, 1H), 7.18 (t, 1H), 6.68 (d, 1H), 6.6 (t, 1H), 4.45 (d, 1H), 4.0 (d, 1H), 3.65 (bs, 1H), 3.5 (s, 2H), 3.35 (t, 1H), 3.1 (t, 1H), 2.2 (m, 2H), 1.5 (m, 2H).

Provenance & Evidence