反应详情

2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Ex-Va, 60 mg, 0.139 mmol), 2-aminoethanol (12.75 mg, 0.209 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=29.5 min) to provide 2-hydroxy-N-(2-hydroxyethyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (40 mg, 0.078 mmol, 56.4% yield) as a single enantiomer. LCMS=475.2 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.15 (2 H, d, J=8.36 Hz), 7.52-7.73 (7 H, m), 5.14 (1 H, s), 3.64 (2 H, t), 3.38 (2 H, td, J=5.67, 3.63 Hz), 2.15 (1 H, s); HPLC peak RT=8.4 min (Method A).

1. customwas 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=29.5 min)