Diisopropylethylamine → (E)-N-(2-Ethoxy-3-isopropylbenzyl)-N-methyl-3-(7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)acrylamide

Participants

Reaction Steps

A solution of (2-ethoxy-3-isopropylbenzyl)methylamine (0.223 g, 1.07 mmol) and diisopropyl-ethylamine (0.51 mL, 2.94 mmol) in DMF (20 mL) was treated sequentially with (E)-3-(7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)acrylic acid hydrochloride (0.250 g, 0.981 mmol), 1-hydroxybenzotriazole hydrate (0.144 g, 1.07 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.205 g, 1.07 mmol). After stirring for 18 h, the reaction mixture was diluted with H2O (30 mL). The resulting solids were collected by filtration, and when washed with Et2O (50 mL), unexpectedly dissolved. The filtrate was extracted with EtOAc (3×50 mL). The combined organics were washed with brine (2×100 mL), dried over Na2SO4, filtered and concentrated to a light orange solid. Purification by column chromatography (silica gel, CH2Cl2/MeOH, 100 to 99.5:0.5) gave the title compound (0.20 g, 52%) as a white solid and as a mixture of amide rotamers: 1H NMR (500 MHz, DMSO-d6) δ 10.64-10.61 (m, 1H), 8.37-8.31 (m, 1H), 8.09-7.99 (m, 1H), 7.52-7.49 (m, 1H), 7.28-7.20 (m, 2H), 7.11-7.05 (m, 1H), 6.89-6.86 (m, 1H), 4.81-4.66 (m, 2H), 3.86-3.79 (m, 2H), 3.28-3.25 (m, 1H), 3.11-2.85 (m, 5H), 2.55-2.49 (m, 2H), 1.39-1.35 (m, 3H), 1.19-1.17 (m, 6H); MS (ESI) m/e 408 (M+H)+.

Provenance & Evidence