Water → N-[(4-chlorophenyl)methyl]-6-[(4-fluoro-3,6-dihydro-2H-pyridin-1-yl)methyl]-1-methyl-4-oxo-quinoline-3-carboxamide

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Reaction Steps

To a solution of N-(4-chlorobenzyl)-6-(chloromethyl)-1-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxamide from Preparation No. 35 (60 mg) in 1-methyl-2-pyrrolidinone (3 mL) is added N,N-diisopropylethylamine (0.075 mL) and 4-fluoro-1,2,3,6-tetrahydropyridine hydrochloride from Preparation No. 38 (119 mg). The reaction mixture is stirred at room temperature overnight and then heated at 60° C. for 4 hrs. The mixture is cooled to room temperature and poured into water to precipitate the product. The crude solid is adsorbed onto silica and purified by chromatography (eluent 100% CH2Cl2 (1 L), 0.25% MeOH in CH2Cl2 (1 L), 0.5% MeOH in CH2Cl2 (1 L), 0.75% MeOH in CH2Cl2 (1 L), 1% MeOH in CH2Cl2 (1 L), 1.25% MeOH in CH2Cl2 (1 L), 1.5% MeOH in CH2Cl2 (2 L)). Fractions homogenous by TLC are combined and concentrated to afford 32.2 mg (46%) of the desired product as a white solid.

Provenance & Evidence