反应 #164366

反应方程式

(R/S)-2-Hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid

2-aminoethanol

HATU

4-methylmorpholine

→

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

收率 68.2%

溶剂

DMF

反应条件

后处理

1. 1
   其他was purified by prep HPLC (
2. 2
   洗涤PHENOMENEX® Luna 5u 21.2×100 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid
3. 3
   其他over 18 min

实验过程

(R/S)-2-Hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-IX, 30 mg, 0.070 mmol), 2-aminoethanol (6.37 mg, 0.104 mmol), HATU (34.4 mg, 0.090 mmol), and 4-methylmorpholine (28.1 mg, 0.278 mmol) were added to DMF (1 mL). It was stirred for 1 h and then 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 18 min, product retention=17.9 min (20 mL/min, 220 nM) to provide (R/S)-2-hydroxy-N-(2-hydroxyethyl)-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (25 mg, 0.047 mmol, 68.2% yield): LCMS=475.1 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.25 (1 H, t, J=5.94 Hz), 8.09-8.19 (2 H, m), 7.58-7.84 (7 H, m), 5.14 (1 H, s), 3.60-3.67 (2 H, m), 3.34-3.44 (2 H, m); HPLC peak RT=8.2 min (Method A).

来源