1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (E)-6-(3-(3-(Benzo[b]thiophen-2-ylmethoxy)azetidin-1-yl)-3-oxoprop-1-enyl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one

Participants

Reaction Steps

3-(Benzo[b]thiophen-2-ylmethoxy)-azetidine hydrochloride (136 mg, 0.76 mmol), EDCI (146 mg, 0.76 mmol), HOBt (103 mg, 0.76 mmol) and diisopropylethylamine (222 μL, 1.27 mmol) were successively added to a solution of (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-acrylic acid hydrochloride (130 mg, 0.51 mmol) in dimethylformamide (10 mL) at room temperature. The reaction mixture was stirred for 3 days. The reaction mixture was then diluted by addition of ethyl acetate (50 mL) and water (50 mL). The aqueous phase was extracted with ethyl acetate (3×100 mL) and dichloromethane (3×100 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×50 mL), dried over sodium sulfate and concentrated to dryness. The residue was purified by chromatography on silica gel using dichloromethane/methanol (1:0 to 95:5) as eluent. After trituration in acetone and methanol, the title product was obtained as a white solid (112 mg, 45%).

Provenance & Evidence