4-Methylmorpholine → 2-hydroxy-N-(2-(methylamino)-2-oxoethyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide

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, 60 mg, 0.139 mmol), 2-amino-N-methylacetamide (12.26 mg, 0.139 mmol), 4-methylmorpholine (56.3 mg, 0.556 mmol), and HATU (68.8 mg, 0.181 mmol) were added to DMF (1 mL). The mixture was stirred for 1 h before it was purified by prep HPLC (PHENOMENEX® Luna 5u 21×250 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 30 min, 25 mL/min, 220 nM, product retention=29.4 min) to provide 2-hydroxy-N-(2-(methylamino)-2-oxoethyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (13 mg, 0.025 mmol, 18.02% yield) as a single enantiomer. LCMS=502.2 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.10-8.25 (2 H, m), 7.53-7.82 (7 H, m), 5.20 (1 H, s), 3.77-4.01 (2 H, m), 2.75 (3 H, s); HPLC peak RT=8.4 min (Method A).

Provenance & Evidence