Dimethylformamide → Trifluoroacetic acid

Participants

Reaction Steps

(R/S)-2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-V, 17 mg, 0.039 mmol), (1,3-dimethyl-1H-pyrazol-5-yl)methanamine (7.40 mg, 0.059 mmol), 4-methylmorpholine (15.95 mg, 0.158 mmol), and HATU (19.48 mg, 0.051 mmol) were dissolved in 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=13.0 min) to provide (R/S)-N-((1,3-dimethyl-1H-pyrazol-5-yl)methyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide, TFA (7 mg, 10.22 μmol, 25.9% yield): LCMS=539.3 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.11-8.23 (2 H, m), 7.52-7.76 (7 H, m), 6.06 (1 H, s), 5.18 (1 H, s), 4.44 (2 H, s), 3.77 (3 H, s), 2.21 (3 H, s); HPLC peak RT=9.0 min (Method A).

Provenance & Evidence