Triethylamine → 4-Chloro-6-fluoro-1-(4-methoxybenzyl)-2-oxo-1,2-dihydro-[1,8]-naphthyridine-3-carbonitrile

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Reaction Steps

A solution of 6-fluoro-4-hydroxy-1-(4-methoxy-benzyl)-2-oxo-1,2-dihydro-[1,8]-naphthyridine-3-carboxylic acid cyclohexylamide (92) (7.46 g, 17.53 mmol) and triethylamine (6.1 mL, 43.83 mmol) was heated in neat POCl3 overnight at 90° C. The solution was cooled and the excess POCl3 was distilled under vacuum. The residue was suspended in saturated NaHCO3 solution, sonicated briefly and filtered. The solids were dissolved in dichloromethane, washed subsequently by saturated NaHCO3 solution, water and brine. The organic phase was dried over MgSO4 and evaporated to yield 4.2 g (69%) of 4-chloro-6-fluoro-1-(4-methoxybenzyl)-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carbonitrile (94) as white solids. MP 195° C. 1H-NMR (DMSO-d6): δ 3.69 (s, 3H), 5.51 (s, 2H), 6.82 (d, J=8.8 Hz, 2H), 7.29 (d, J=8.8 Hz, 2H), 8.48 (dd, J=2.8, 8.4 Hz, 1H), 8.96 (d, J=2.8 Hz, 1H); EIMS m/z 344 (M+1).

Provenance & Evidence