Hydrochloric Acid → Gsk-364735

Participants

Reaction Conditions

Reaction Steps

To a solution of ethyl 7-[(4-fluorophenyl)methyl]-4-hydroxy-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate (143.3 g, 0.402 mol) in EtOH (1.3 L) was added NMP (0.5 L) and ethanolamine (27.75 g, 0.454 mol). Distilled EtOH over a period of 2 h and the resulting reaction mixture was heated at 110° C. for 45 min. Cooled to 60° C. and added water dropwise (0.47 L), followed by addition of 1N HCl (0.2 L) to pH 2-3. Cooled to room temperature and diluted by dropwise addition of water (1.2 L). The solids which precipitated were collected by filtration, washed with water and dried under vacuum at 70° C. to afford a tan solid. 1H NMR (d6-DMSO) δ 10.41 (1H, t, J=5.5 Hz), 8.53 (1H, s), 8.00 (1H, s), 7.39-7.35 (2H, m), 7.15-7.10 (2H, m), 4.92 (1H, t, J=5 Hz), 4.15 (2H, s), 3.58 (3H, s), 3.55-3.53 (2H, m), 3.44-3.40 (2H, m); ES+ MS: 372 (M+H+, 100).

Provenance & Evidence