反应 #164369

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

3-(1H-imidazol-1-yl)propan-1-amine

HATU

4-methylmorpholine

DMF

→

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

收率 42.3%

反应条件

后处理

1. 1
   其他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=10.5 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), 3-(1H-imidazol-1-yl)propan-1-amine (13.06 mg, 0.104 mmol), HATU (34.4 mg, 0.090 mmol), and 4-methylmorpholine (28.1 mg, 0.278 mmol) were dissolved in DMF (1 mL). This 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 10 min, 20 mL/min, 220 nM, product retention=10.5 min) to provide (R/S)-N-(3-(1H-imidazol-1-yl)propyl)-2-hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide-TFA (20 mg, 0.029 mmol, 42.3% yield): LCMS=539.2 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.90 (1 H, s), 8.13-8.19 (2 H, m), 7.52-7.83 (9 H, m), 5.16 (1 H, s), 4.23 (2 H, td, J=6.88, 3.41 Hz), 3.26-3.31 (2 H, m), 2.12 (2 H, dq, J=6.82, 6.68 Hz); HPLC peak RT=7.8 min (Method A).

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