4-Methylmorpholine → 2-hydroxy-N-(1-(4-methyl-4H-1,2,4-triazol-3-yl)ethyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide

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), (R/S)-1-(4-methyl-4H-1,2,4-triazol-3-yl)ethanamine (7.46 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=12.2 min) to provide 2-hydroxy-N-(1-(4-methyl-4H-1,2,4-triazol-3-yl)ethyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (8 mg, 0.014 mmol, 34.6% yield) as a racemic mixture of diastereomers. LCMS=540.3 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.90 (1 H, s), 8.16 (2 H, d, J=8.36 Hz), 7.52-7.77 (7 H, m), 5.36 (1 H, q), 5.21 (1 H, s), 3.62 (3 H, s), 1.69 (3 H, d, J=7.04 Hz); HPLC peak RT=8.4 min (Method A).

Provenance & Evidence