Diisopropylethylamine → 5-[ethylsulfonyl(methyl)amino]-N-[[4-fluoro-2-(methylcarbamoyl)phenyl]methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide

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Reaction Steps

8-Hydroxy-5-[methyl(ethylsulfonyl)amino]-1,6-naphthyridine-7-carboxylic acid was coupled with {2-[(methylamino)carbonyl]4-fluorophenyl}methanaminium chloride (prepared as described in Example 3). A solution of 8-Hydroxy-5-[methyl(ethylsulfonyl)amino]-1,6-naphthyridine-7-carboxylic acid (50 mg, 0.16 mmol) in dry DMF (15 mL) was stirred at zero degrees. To this was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (40 mg, 0.21 mmol), 1-hydroxy-7-azabenzotriazole (28 mg, 0.21 mmol). The mixture was stirred for 35 minutes at which time the {4-fluoro-2-[(methylamino)carbonyl]phenyl}-methanaminium chloride (38 mg, 0.21 mmol) and diisopropylethylamine (27 mg, 0.21 mmol) was added and the reaction was stirred at room temperature overnight. The reaction was filtered through a glass fiber filter. The filtrate was vacuum reduced and purified by preparative HPLC (Gilson semi preparative HPLC system using a Waters Nova pak column (10×40 mm I.D. cartridges, C18, 6 μM pore size) eluting with 95-5% water (0.025% TFA)/acetonitrile (0.025% TFA) at 35 mL/min). The desired fractions were freeze dried to give the desired product as a white solid.

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