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, 25 mg, 0.058 mmol), 2-pyrazin-2-yl-ethylamine (10.71 mg, 0.087 mmol), HATU (28.7 mg, 0.075 mmol), and 4-methylmorpholine (23.45 mg, 0.232 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 12 min, 20 mL/min, 220 nM, product retention=13.6 min) to provide 2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)-N-(2-(pyrazin-2-yl)ethyl)acetamide, TFA (10 mg, 0.018 mmol, 30.6% yield) as a single enantiomer. LCMS=537.4 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.05-8.58 (5 H, m), 7.49-7.78 (7 H, m), 5.06 (1 H, s), 3.67 (2 H, dt, J=13.59, 6.74 Hz), 3.05 (2 H, t, J=6.71 Hz); HPLC peak RT=9.1 min (Method A).

Provenance & Evidence