Potassium Carbonate → HCID 68746132, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of palladium (II) acetate (22.95 mg, 0.10 mmol, 0.1 equiv.) and 1,1′-bis(di-t-butylphosphino)ferrocene (48.5 mg, 0.10 mmol, 0.1 equiv.) in acetonitrile (3 mL) was added ethyl 6-bromo-1-((1-methyl-1H-pyrazol-4-yl)methyl)-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylate (Intermediate 52, 400 mg, 1.02 mmol, 1 equiv.), followed by 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazole-2-yl)pyridine-3-ylboronic acid (WO2009106885, 372 mg, 1.03 mmol, 1.01 equiv.) and a solution of potassium carbonate (212 mg, 1.53 mmol, 1.5 equiv.) in water (1 mL). The reaction mixture was stirred at 60° C. for 9 h. The reaction mixture was concentrated under reduced pressure and resuspended in 1,4-dioxane (3 mL). 2 M Lithium Hydroxide (1.02 mL) was added, and the reaction mixture as stirred at 100° C. for 4 h. The reaction mixture was cooled to room temperature and diluted with water. 1 N HCl was added until pH 3-4 was reached. The precipitate was washed with water and hexanes and dried. The compound was purified (silica gel chromatography) and concentrated to provide 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-((1-methyl-1H-pyrazol-4-yl)methyl)-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylic acid (90.7 mg, 15%). Calcd for C26H21F3N8O4S [M+H]+: 599.16. H1NMR (d6-DMSO) δ 14.42 (s, 1H), 9.54 (s, 1H), 9.52 (s, 1H), 9.25 (s, 1H), 8.55 (s, 1H), 8.54 (s, 1H), 8.25 (s, 1H), 8.13 (s, 1H), 7.82 (s, 1H), 7.58 (t, 1H), 7.53 (s, 1H), 5.75 (s, 2H), 3.76 (s, 3H), 3.26-3.17 (m, 2H), 1.11 (t, 3H).

Provenance & Evidence