4-Methylmorpholine → (R/S)-N-(1-cyano-2-phenylethyl)-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

2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-Va, 20 mg, 0.046 mmol), (R/S)-2-amino-3-phenylpropanenitrile hydrochloride (8.47 mg, 0.046 mmol), 4-methylmorpholine (18.76 mg, 0.185 mmol), and HATU (22.92 mg, 0.060 mmol) were added to DMF (2 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 (R/S)-N-(1-cyano-2-phenylethyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (8 mg, 0.012 mmol, 26.2% yield) as a mixture of diastereomers: LCMS=546.3 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.05-8.17 (2 H, m), 7.18-7.72 (12 H, m), 5.08-5.15 (1 H, m), 5.02 (1 H, t, J=7.70 Hz), 3.11-3.27 (2 H, m); HPLC peak RT=11.0 min (Method A).

Provenance & Evidence