Phenyl Isothiocyanate → (RS) 3-{5-[2-(2-Phenylamino-benzoxazol-6-yl)-acetylamino]-pyridin-2-yl}-butyric acid

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A solution of (RS) methyl 3-{5-[2-(4-amino-3-hydroxy-phenyl)-acetylamino]-pyridin-2-yl}-butyrate (41.2 mg, Reference Example 24) in ethanol (1 mL) was treated with a solution of phenyl isothiocyanate (16.23 mg) in ethanol (2 mL). The mixture allowed to stand at room temperature for 48 hours, then heated at 70° C. for 16 hours and then evaporated. The residue, (RS) methyl 3-{5-[2-(3-hydroxy-4-(3-phenylthioureido)-phenyl)-acetylamino]-pyridin-2-yl}-butyrate, was dissolved in dry dimethylformamide (1 mL) and the solution was treated with a solution of dicyclohexylcarbodiimide (74.2 mg) in dry dimethylformamide (2 mL). This mixture was heated at 70° C. for 12 hours and then evaporated. The residue was dissolved in methanol (2 mL) and the solution was treated with aqueous sodium hydroxide (600 μL, 1M). After shaking for 24 hours the mixture was filtered and the filtrate was acidified with aqueous acetic acid (1 mL, 1M). The precipitate was filtered and dissolved in dimethylformamide. This solution was evaporated and the residue was subjected to reversed phase HPLC on a Hypersil Elite C18 column (100 mm×21 mm) using 0.05% TFA in acetonitrile water to give the title compound. LC-MS: RT=2.36 minutes; MS (ES+): 431 (MH+).

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