Cesium carbonate → Ethyl 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

Participants

Reaction Conditions

Reaction Steps

In a round bottomed flask, ethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 15, 400 mg, 1.3 mmol), 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 9, 700 mg, 1.72 mmol) and cesium carbonate (3.78 g, 2.46 mmol) were combined and suspended in 10 mL of dioxane:water (8:2). The suspension was purged with argon for 15 min. then tetrakis (triphenylphosphine) palladium (140 mg, 0.2 mmol) was added under argon atmosphere and the reaction mixture was heated to 80-90° C. for 5 h. After completion of the reaction, the reaction mixture was cooled to room temperature and filtered through celite. The filtrate was concentrated under reduced pressure to a residue, to which acetonitrile was added. The precipitated solid was filtered and dried to afford 150 mg (25%) of ethyl 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.

Provenance & Evidence