Sodium Carbonate → 3-{[Bis(benzyloxy)phosphoryl]oxy}propyl 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 Steps

3-{[Bis(benzyloxy)phosphoryl]oxy}propyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 26, 750 mg, 1.21 mmol) was dissolved in dimethylformamide (25 mL) and the solution was purged with argon. Tetrakis (triphenylphosphine) palladium (145 mg, 0.12 mmol) followed by 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 9, 645 mg, 1.46 mmol) was added and the mixture was stirred for 20 min at room temperature. Sodium carbonate solution (516 mg, 4.87 mmol) (dissolved in minimum amount of water) was added to reaction mixture and it was heated to 90° C. for 3 h. The reaction mixture was passed through celite bed and the celite was washed with dimethylformamide. The dimethylformamide layer was poured into water (100 mL) and a precipitate formed. The solid was filtered and dried then purified by flash column chromatography over silica gel (100-200 mesh). The product was eluted with gradient of MeOH/CHCl3 (0-6%) to afford 650 mg (65%) 3-{[bis(benzyloxy)phosphoryl]oxy}propyl 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