Sodium Carbonate → 2-Hydroxyethyl 1-ethyl-6-{6-[(ethylcarbamoyl)amino]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-3-yl}-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate

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Reaction Steps

2-Hydroxyethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 23, 170 mg, 0.50 mmol) was dissolved in dimethylformamide (25 mL), purged with argon, tetrakis (triphenylphosphine) palladium (57 mg, 0.049 mmol) followed by 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 9, 264 mg, 0.598 mmol) was added and stirred for 20 min at room temperature, sodium carbonate solution (231 mg, 2 mmol) (dissolved in minimum amount of water) was added to reaction mixture and the mixture was heated to 90° C. for 3 h. The reaction mixture was passed through a celite bed and the celite was washed with dimethylformamide. The dimethylformamide layer was poured into water (100 mL) and a solid precipitate formed. The solid was filtered and dried then purified by flash column chromatography over silica gel (100-200 mesh) using MeOH (0-6%) in CHCl3 as an eluent to afford 168 mg (60%) 2-hydroxyethyl 1-ethyl-6-{6-[(ethylcarbamoyl)amino]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-3-yl}-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate as white solid.

Provenance & Evidence