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

Participants

Reaction Steps

To a stirred solution of N-biphenyl-4-yl-malonamic acid (0.101 g, 0.00039 mole) in DMF (3 mL) was added DIPEA (0.233 g, 0.0018 mole), HOBt (0.053 g, 0.00039 mole) and EDCI.HCl (0.138 g, 0.00072 mole). After 2 minutes (2,3-dimethyl-phenyl)-piperidin-4-yl-amine dihydrochloride (0.1 g, 0.00036 mole) 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 silica gel 60-120 mesh (1% methanol in chloroform) afforded 0.07 g (44%) of N-biphenyl-4-yl-3-[4-(2,3-dimethyl-phenylamino)-piperidin-1-yl]-3-oxo-propionamide. LC-MS purity: 442.24 (M+1)+, 95.5%, 1H NMR (DMSO-d6): δ 10.2 (s, 1H), 7.7 (m, 6H), 7.6 (t, 2H), 7.4 (d, 1H), 6.8 (t, 1H), 6.5 (d, 1H), 6.4 (d, 1H), 4.4 (t, 2H), 4.0 (d, 1H), 3.6 (bs, 3H), 3.2 (t, 1H), 2.8 (t, 1H), 2.2 (s, 3H), 2.0 (bs, 5H), 1.5 (d, 1H), 1.4 (d, 1H).

Provenance & Evidence