Hydrochloric Acid → 5-{1'-[(8-Cyclopropyl-4-methoxy-quinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4'-piperidin]-6-yl}nicotinic acid

Participants

Reaction Conditions

Reaction Steps

5-{4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinic acid di-hydrochloride (4.93 g, 12.0 mmol), TEA (5.14 mL, 36.9 mmol) were suspended in DMF (49 mL) and (8-cyclopropyl-4-methoxy-quinolin-2-yl)-imidazol-1-yl-methanone (2.70 g, 9.22 mmol) was added thereto at room temperature, and the reaction mixture was stirred at 70° C. for 19 h. After cooled to room temperature, the mixture was poured into 1N HCl aq. (27.7 mL, 27.7 mmol) in H2O (367 mL) solution and the suspension was stirred for 2 h. The resulting precipitate was filtered, washed with H2O to give crude intended compound as a pale brown solid. This solid was washed with EtOAc-MeOH (1:1), then EtOH, and dried to afford the intended compound as a colorless solid. 1H-NMR (400 MHz, DMSO-d6) δ: 9.08 (1.0H, d, J=2.4 Hz), 9.03 (1.0H, d, J=2.0 Hz), 8.41 (1.0H, dd, J=2.0, 2.4 Hz), 8.07-8.03 (2.0H, m), 7.94 (1.0H, dd, J=8.3, 1.5 Hz), 7.49 (1.0H, dd, J=8.3, 7.6 Hz), 7.30-7.23 (2.0H, m), 7.20 (1.0H, s), 4.40-4.33 (1.0H, m), 4.07 (3.0H, s), 3.94-3.87 (1.0H, m), 3.57-3.48 (1.0H, m), 3.39-3.24 (1.0H, m), 3.11-3.04 (1.0H, m), 2.98 (2.0H, s), 2.15-2.07 (1.0H, m), 2.03-1.79 (3.0H, m), 1.10-1.04 (2.0H, m), 0.87-0.72 (2.0H, m). MS [M+H]+=564.

Provenance & Evidence