Acetohydrazide → Tert-butyl 1-(4-(2-acetylhydrazinecarbonyl)-6-fluoro-3-(pyridin-2-yl)quinolin-2-yl)ethylcarbamate

Participants

Reaction Steps

A solution of 2-(1-(tert-butoxycarbonylamino)ethyl)-6-fluoro-3-(pyridin-2-yl)quinoline-4-carboxylic acid (2.011 g, 4.89 mmol) and acetic hydrazide (0.543 g, 7.33 mmol) in DCM (10.99 mL) and DMF (1.222 mL) was treated 0° C. with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl) (2.81 g, 14.66 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (HOAt) (1.995 g, 14.66 mmol), and sodium bicarbonate (1.232 g, 14.66 mmol) successively at 0° C. Then the reaction was stirred at rt. After 15 h, the reaction was partitioned between DCM (100 mL) and 1.0 M aq LiCl (100 mL). The separated aq layer was extracted with DCM (1×100 mL) and the combined organic extracts were washed with 1.0 M aq LiCl (100 mL), dried over MgSO4 and concentrated in vacuo. The crude material was purified by silica gel column chromatography eluting with a gradient of 0% to 50% EtOAc in hexane, to provide tert-butyl 1-(4-(2-acetylhydrazinecarbonyl)-6-fluoro-3-(pyridin-2-yl)quinolin-2-yl)ethylcarbamate as off-white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 10.44 (1H, s), 9.81 (1H, s), 8.69 (1H, d, J=4.7 Hz), 8.37 (1H, dd, J=10.4, 2.7 Hz), 8.16 (1H, dd, J=9.2, 5.5 Hz), 7.93 (1H, td, J=7.7, 1.8 Hz), 7.77 (1H, td, J=8.8, 2.7 Hz), 7.56 (1H, d, J=7.6 Hz), 7.47 (1H, dd, J=7.0, 5.3 Hz), 7.02 (1H, d, J=7.6 Hz), 4.70-4.82 (1H, m), 1.87 (3H, s), 1.31 (9H, s), 1.22 (3H, d, J=6.7 Hz); LC-MS (ESI) m/z 468.1 [M+H]+.

Provenance & Evidence