Dimethylformamide → (R)-3-[N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-(5-oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl)-hydrazino]-2-hydroxypropionic Acid Ethyl Ester

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Reaction Steps

5-Oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carboxylic acid (89.5 mg, 436 μmol) was combined with HCTU (244 mg, 589 μmol) in DMF (1.0 mL, 13 mmol) and stirred for 10 minutes. (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid ethyl ester (80.0 mg, 0.2 mmol) and DIPEA (0.1 mL, 0.7 mmol) were added, and the resulting mixture was stirred overnight. The mixture was diluted with EtOAc (10.0 mL) and washed with water (3.0 mL), saturated aqueous NaHCO3 (2×3.0 mL), and saturated aqueous NaCl (3.0 mL), then dried over Na2SO4, filtered and concentrated to give a yellowish solid. A portion (20 mg) of the solid was dissolved in AcOH (1.5 mL), filtered and purified by reverse phase preparative HPLC to yield the title compound (1.6 mg, purity 100%). MS m/z [M+H]+ calc'd for C27H23ClFN3O3, 554.15. found 554.4.

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