Dichloromethane → 4-Benzylamino-6-methoxy-[1,5]naphthyridin-3-ol

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Reaction Steps

Tris(dibenzylideneacetone)dipalladium(0) (10 mg, 0.011 mmol, 0.04 eq) is added at room temperature to a stirred solution of benzyl-(3-bromo-6-methoxy-[1,5]naphthyridin-4-yl)-amine (100 mg, 0.29 mmol, 1.0 eq) in dioxane (6 mL) and water (3 mL), followed by (4′,6′-diisopropyl-3,4,5,6,2′-pentamethyl-biphenyl-2-yl)-dimethyl-phosphane (8 mg, 0.016 mmol, 0.06 eq). After 10 minutes stirring at room temperature, a solution of potassium hydroxide (82 mg, 1.46 mmol, 5.0 eq) in water (3 mL) is added and the resulting mixture is stirred at 105° C. for 16 hours. The reaction mixture is cooled down to room temperature, extracted with ethyl acetate (3×10 mL) and water (10 mL) and the pH is adjusted to 6 by the addition of a 1N hydrochloric acid aqueous solution. The combined organic layers are dried over sodium sulfate, filtered and concentrated to give the crude product that is purified by column chromatography (silica gel, eluent: dichloromethane:methanol, 5:1, v/v) to afford 4-benzylamino-6-methoxy-[1,5]naphthyridin-3-ol as a light yellow solid (30 mg, 36% yield).

Provenance & Evidence