Dimethylformamide → Trifluoroacetic acid

Participants

Reaction Steps

2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-Va, 20 mg, 0.046 mmol), (S)-1-(1H-imidazol-2-yl)ethanamine (5.15 mg, 0.046 mmol), HATU (22.92 mg, 0.060 mmol), and 4-methylmorpholine (18.76 mg, 0.185 mmol) were added to DMF (1 mL). This was stirred for 1 h before it was purified by prep HPLC (PHENOMENEX® Luna 5u 21.2×100 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 10 min, 20 mL/min, 220 nM, product retention=11.3 min) to provide N-((S)-1-(1H-imidazol-2-yl)ethyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide, TFA (17 mg, 0.021 mmol, 44.4% yield) as a single enantiomer. LCMS=525.3 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.10-8.27 (2 H, m), 7.42-7.77 (11 H, m), 5.26-5.33 (1 H, m), 5.23 (1 H, s), 1.68 (3 H, d, J=7.26 Hz); HPLC peak RT=8.4 min (Method A).

Provenance & Evidence