Heptane → N-(2-diethylaminoethyl)-1,4-dihydro-6-iodo-4-oxoquinoline-3-carboxamide

Participants

Reaction Steps

To a stirred solution of a 2.0 M trimethylaluminium solution in heptane (20.8 mL, 41.6 mmol) in anhydrous dichloromethane (350 mL) was added at 0° C., under argon, N,N-diethylethylenediamine (5.78 mL, 41.1 mmol) dropwise. After 10 min, ethyl 6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylate (93) (10.0 g, 31.4 mmol) (Edlin, C.; Eldred, C. D.; Lunniss, C. J.; Redgrave, A. J.; Robinson, J. E.; Woodrow, M. Preparation of aminocarbonylquinoline derivatives as phosphodiesterase type IV (PDE4) inhibitors. Patent WO2005030725, 2005) was added. The mixture was refluxed for 12 h. After cooling to room temperature, water (500 mL) was added and the precipitate was filtered and washed with ethanol (2×100 mL). The filtrate was evaporated under vacuum. The residue was chromatographed (Al2O3, CH2Cl2/EtOH, 94/6, v/v) to give amide 94 (9.70 g, 23.5 mmol) as a beige solid. Yield 81%; Rf (Al2O3, CH2Cl2/EtOH, 94/6, v/v) 0.32; mp 243-245° C.; IR (KBr) ν 1466, 1507, 1551, 1633, 2800-3000, 3062 cm−1; 1H NMR (200 MHz, DMSO-d6) δ 1.23 (t, 6H, J=7.1 Hz), 3.17 (q, 4H, J=7.1 Hz), 3.23 (t, 2H, J=6.8 Hz), 3.71 (q, 2H, J=6.4 Hz), 7.59 (d, 1H, J=8.6 Hz), 8.05 (dd, 1H, J=2.0, 8.6 Hz), 8.51 (d, 1H, J=2.0 Hz), 8.72 (s, 1H), 10.04 (t, 1H, J=5.8 Hz), 10.13 (se, 1H); ESI-MS m/z 413.8 [M+H]+.

Provenance & Evidence