4-Methylmorpholine → HCID 53495244, compound

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, 40 mg, 0.093 mmol) and (R)-2-aminopropanenitrile (Int-X, 13.00 mg, 0.185 mmol) were dissolved in DMF (1 mL). 4-Methylmorpholine (37.5 mg, 0.371 mmol) and HATU (45.8 mg, 0.121 mmol) were added. After stirring 1 h, the mixture was purified by prep HPLC (PHENOMENEX® Luna 5u 21.2×250 mm, gradient elution with Method 2—CH3CN/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 35 min, 20 mL/min, 220 nM, product retention=28.5 min) to provide single enantiomer N-((R)-1-cyanoethyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (27 mg, 0.055 mmol, 59.6% yield): [M+H]+=484.0; 1H NMR (400 MHz, methanol-d4) δ ppm 8.93 (1 H, d, J=7.70 Hz), 8.13-8.24 (2 H, m), 7.50-7.80 (7 H, m), 5.17 (1 H, s), 4.86-4.91 (1 H, m), 1.56 (3 H, d, J=7.04 Hz); HPLC peak RT=9.9 min (Method A).

Provenance & Evidence