Sodium Hydroxide → 4,4,4-Trifluoro-3-(3-fluoro-4-(2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenylamino)butanoic acid

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Reaction Steps

A solution of 319 (490 mg, 0.84 mmol) and sodium hydroxide (338 mg, 8.44 mmol) in water (0.7 mL) and ethanol (3.4 mL) was stirred at room temperature for 48 h. The solvents were removed under reduced pressure and the residue was dissolved in water (20 mL). The solution was neutralized to pH 4 with a 3N HCl solution and the solid thus formed was filtered off, rinsed with water and dried. The solid was suspended in dry toluene (20 mL), heated to reflux for 1 h under continuous stirring, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent MeOH-dichloromethane, gradient 10:90 to 50:50) and the resulting solid was triturated in a mixture of dichloromethane, ethyl acetate and hexane, isolated by filtration, and dried under high vacuum to afford title compound 320 (150 mg, 0.31 mmol, 37% yield). LRMS (M+1) 480.9 (100%).

Provenance & Evidence