Triethylamine → 5-(1,1-dioxothiazinan-2-yl)-N-[[4-fluoro-2-(isopropylcarbamoyl)phenyl]methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide

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Reaction Steps

5-(1,1-Dioxido-1,2-thiazinan-2-yl)-8-hydroxy-1,6-naphthyridine-7-carboxylic acid (200 mg, 0.62 mmol, prepared as described in Example 3, Step 7), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (154 mg, 0.80 mmol), and 1-hydroxy-7-azabenzotriazole (109 mg, 0.80 mmol) were added to dry DMF (15 mL) and stirred for 30 minutes to preform the activated ester. {4-Fluoro-2-[(isopropylamino)carbonyl]phenyl}methanaminium chloride (168 mg, 0.68 mmol) and triethylamine (95 μL, 0.68 mmol) were added and the reaction was stirred overnight at room temperature. The reaction was poured into water, the pH was adjusted to ˜10 using 1N NaOH, and resulting solution was extracted several times with CHCl3. The combined organic extracts were dried over Na2SO4, filtered, and concentrated to dryness in vacuo. The residue was redissolved in basic water and CHCl3, acidified to pH=4 using 1N HCl and extracted several times with CHCl3. The combined organic extracts were dried over Na2SO4, filtered, and concentrated to a whitish solid. Methanol was added to the flask and the flask was sonicated for 5 minutes. The resulting solids were collected by vacuum filtration to give the title compound as an off-white solid.

Provenance & Evidence