1-Hydroxybenzotriazole → (E)-N-methyl-N-((1-methyl-1H-indol-4-yl)methyl)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide

Participants

Reaction Conditions

Reaction Steps

To a solution of N-methyl(1-methyl-1H-indol-4-yl)methanamine (418 mg, 2.40 mmol), 3-(7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)-acrylic acid hydrochloride (617 mg, 2.42 mmol), HOBt (327 mg, 2.42 mmol) and DIPEA (1.71 mL, 9.82 mmol) in anhydrous DMF (40 mL) was added EDC hydrochloride (460 mg, 2.40 mmol). The mixture was stirred overnight at 40° C. Water (60 mL) was added and the solution was stirred for 1 h. The reaction mixture was extracted with CH2Cl2 (3×100 mL). Combined organic layers were washed with water (50 mL) and brine (50 mL) and concentrated to give a red solid which was purified by column chromatography (silica gel, 5% MeOH/CH2Cl2) to afford (E)-N-methyl-N-((1-methyl-1H-indol-4-yl)methyl)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide (320 mg, 36%) as a pink solid and a mixture of amide rotomers: 1H NMR (400 MHz, DMSO-d6) δ 10.64-10.61 (m, 1H), 8.36-8.32 (m, 1H), 8.07-7.98 (m, 1H), 7.56-7.51 (m, 1H), 7.37-7.23 (m, 3H), 7.19-7.09 (m, 1H), 6.92-6.79 (m, 1H), 6.49-6.48 (m, 1H), 5.05-4.87 (m, 2H); 3.78-3.77 (m, 3H), 3.01-2.82 (m, 5H), 2.54-2.52 (m, 2H); ESI MS m/z 375 [C22H22N4O2+H]+.

Provenance & Evidence