Hydrochloric Acid → (R)-3-{N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic Acid Isobutyl Ester

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Reaction Steps

3-(2-fluorophenyl)isoxazole-5-carboxylic acid (15.4 mg, 74 μmol) and HATU (33.9 mg, 89 μmol) were stirred in DMA (0.5 mL, 5 mmol) for 10 minutes. (R)-3-[N-(5′-Chloro-2′-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid ethyl ester (27.3 mg, 74 μmol) and DIPEA (38.9 μL, 223 μmol) were added, and the resulting mixture was stirred at room temperature for 1 hour. The mixture was then concentrated under reduced pressure, and the residue was dissolved EtOAc (20 mL) and washed with water (2×2 mL). The organic layer was dried over MgSO4, filtered, and concentrated. The product was then mixed with isobutyl alcohol (0.5 mL, 5 mmol) and 4.0 M HCl in 1,4-dioxane (93 μL, 372 mmol), and stirred at room temperature overnight. The mixture was concentrated under reduced pressure, and the residue was dissolved in 50% AcOH-water (1.5 ml), filtered, and purified by reverse phase preparative HPLC to yield the title compound (1.7 mg, purity 100%) as a TFA salt. MS m/z [M+H]+ calc'd for C30H28ClF2N3O5, 584.17. found 584.4.

Provenance & Evidence