Hydrochloric Acid → 2-amino-1-[3-(trifluoromethyl)phenyl]-1,8-naphthyridin-4(1H)-one

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Reaction Steps

Ethyl 2-cyano-3-oxo-3-(2-{[3-(trifluoromethyl)phenyl]amino}-3-pyridinyl)propanoate (2.0 g, 5.3 mmol) was heated to 120° C. in a mixture of conc. HCl (4 mL) and glacial acetic acid (2 mL) for 3 h. The reaction mixture was cooled to room temperature, and neutralized by slow addition of NaOH pellets. The mixture was extracted with CH2Cl2 (3×). The combined organic extracts were washed with saturated aqueous NaHCO3 (10 mL) and brine (10 mL), dried over MgSO4, and concentrated in vacuo. The residue was purified by prep-HPLC (YMC-Pack Pro C18 Column, 150×20 mm I.D.; 30–70% CH3CN in water, 20 min.) to afford 2-Amino-1-[3-(trifluoromethyl)phenyl]-1,8-naphthyridin-4(1H)-one (880 mg, 55%): LCMS RT: 2.03 min, MH+: 306.3.

Provenance & Evidence