[NH2:1][C:2]1[C:3]([OH:12])=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].N1C=CC=CC=1.[F:19][C:20]1[CH:28]=[C:27]([C:29]2[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=2)[CH:26]=[CH:25][C:21]=1[C:22](Cl)=[O:23]>C1(C)C=CC=CC=1>[F:19][C:20]1[CH:28]=[C:27]([C:29]2[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=2)[CH:26]=[CH:25][C:21]=1[C:22]([NH:1][C:2]1[C:3]([OH:12])=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6])=[O:23]To a solution of 4-bromo-2-fluorobenzoic acid (4.34 g, 20 mmol) and pyridine-4-ylboronic acid (2.45 g, 20 mmol) in acetonitrile (40 mL) and water (40 mL), potassium carbonate (5.52 g, 40 mmol), bis(triphenylphosphine)palladium(II) chloride (1.08 g, 0.05 mmol) was added. The mixture was degassed and purged withed nitrogen. The mixture was stirred at 100° C. for 24 h. Then the hot suspension was filtered and concentrated to half of the original volume and washed with dichloromethane. The aquatic phase was adjusted to pH 3 with hydrochloric acid (1 M) and filtrated, washed with water. The residue was dried in vacuum to obtain 2-fluoro-4-(pyridine-4-yl)benzoic acid as a white solid (3.15 g, yield 72%. LC-MS (ESI) m/z: 218 (M+1)+.) Thionyl chloride (20 mL) was added to 2-fluoro-4-(pyridine-4-yl)benzoic acid (3.15 g, 14.53 mmol) and the mixture was stirred at 70° C. overnight. The solvent was evaporated under reduced pressure and the residue was dried in vacuum giving 2-fluoro-4-(pyridine-4-yl)benzoyl chloride. To a solution of methyl 3-amino-2-hydroxybenzoate (2.42 g, 14.5 mmol) and pyridine (1.2 mL, 14.5 mmol) in toluene (20 mL) was added 2-fluoro-4-(pyridine-4-yl)benzoyl chloride (3.41 g, 14.5 mmol) portion-wise at 0° C. and then stirred at 70° C. for 4 h. The resulting mixture was extracted with ethyl acetate (100 mL×4), the organic phase was washed with water and saturated sodium bicarbonate, dried with anhydrous sodium sulfate and evaporated under reduced pressure to obtain methyl 3-(2-fluoro-4-(pyridin-4-yl)benzamido)-2-hydroxybenzoate as a yellow solid (3.5 g, yield 65%). LC-MS (ESI) m/z: 367 (M+1)+.
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