Sodium Carbonate → 3-Hydroxypropyl 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

3-Hydroxypropyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 24, 400 mg, 1.46 mmol) was dissolved in dimethylformamide (35 mL) and the solution was purged with argon. Tetrakis (triphenylphosphine) palladium (167 mg, 0.14 mM) followed by 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 9, 775 mg, 1.75 mmol) was added and the mixture was stirred for 20 min at room temperature. Sodium carbonate solution (678 mg, 5.84 mmol) (dissolved in minimum amount of water) was added and the reaction mixture was heated to 90° C. for 3 h. The reaction mixture was passed through celite and the celite was washed with dimethylformamide. The dimethylformamide layer was poured into water (100 mL) and a precipitate formed. The precipitate was filtered and dried then purified by flash column chromatography over silica gel (100-200 mesh) using methanol (5%) in chloroform as eluent to afford 360 mg (65%) 3-hydroxypropyl 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