Acetic Acid → (R/S)-N-(2-acetamidoethyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide

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Reaction Steps

(R/S)-N-(2-Aminoethyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (Example 52, 30 mg, 0.063 mmol), acetic acid (7.61 mg, 0.127 mmol), HATU (36.1 mg, 0.095 mmol), and 4-methylmorpholine (32.0 mg, 0.317 mmol) were added to DMF (1 mL). This was stirred for 30 min and then was purified by prep HPLC (PHENOMENEX® Luna 5u 21.2×100 mm, 20 mL/min, 220 nM, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 15 min (The product retention time was 18.4 min.) to yield (R/S)-N-(2-acetamidoethyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (10 mg, 0.019 mmol, 29.8% yield): LCMS=516.2 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.18 (2 H, d, J=8.35 Hz), 7.54-7.73 (7 H, m), 5.12(1 H, s), 3.34-3.39(2 H, m), 3.24-3.29(2 H, m), 1.89(3 H, s); HPLC peak RT=7.4 min (Method A).

Provenance & Evidence