Trifluoroacetic acid → HCID 178468257, compound

Participants

Reaction Steps

3-[N′-t-Butoxycarbonyl-N-(3′-fluorobiphenyl-4-ylmethyl)-hydrazino]-2-hydroxy-2-methyl-propionic acid methyl ester (100 mg, 231 mmol, 1.0 eq.) was dissolved in DCM (2.0 mL). TFA (2.0 mL) was added and the mixture was stirred at room temperature until the reaction was complete (˜45 minutes). The mixture was then concentrated. 3-Hydroxyisoxazole-5-carboxylic acid (38.8 mg, 300 mmol, 1.3 eq.) and 1 HOAt (40.9 mg, 300 μmol, 1.3 eq.) were dissolved in DMF (2 mL) of DMF, then EDCI (53.2 μL) was added followed by DIPEA (121 μL) and the mixture was stirred for 30 minutes. To this was added the concentrated mixture from above in DMF (2 mL) and the resulting mixture was stirred at room temperature until the reaction was complete (˜2.5 hours). The mixture was then dissolved in THF (2.0 mL), followed by the addition of lithium hydroxide monohydrate (97.0 mg, 2.3 mmol) in water (2.0 mL. The resulting mixture was stirred at room temperature until the reaction was complete (˜1 hour). The reaction was quenched by addition of AcOH, then the solution was concentrated. The crude product was purified by preparative HPLC (10-70% MeCN/water) to yield the title compound (43 mg; purity 99%). MS m/z [M+H]+ calc'd for C21H20FN3O6, 430.13; found 430.4.

Provenance & Evidence