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

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).

1. stirringthe resulting mixture is stirred at 105° C. for 16 hours
2. temperatureThe reaction mixture is cooled down to room temperature
3. extractionextracted with ethyl acetate (3×10 mL) and water (10 mL)
4. additionthe pH is adjusted to 6 by the addition of a 1N hydrochloric acid aqueous solution
5. dry with materialThe combined organic layers are dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customto give the crude product that
9. customis purified by column chromatography (silica gel, eluent

ORD record

ord-745fbc17ed0a49a8917ca69a0bc361d7

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08927541B2