Ethanolamine → 2-hydroxy-N-(2-hydroxyethyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide

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Reaction Conditions

Reaction Steps

(R/S)-2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-V, 130 mg, 0.3 mmol) was dissolved in DMF (2 mL) and cooled to 0° C. prior to the addition of 2-aminoethanol (27.6 mg, 0.452 mmol), 4-methylmorpholine (0.133 mL, 1.206 mmol), and HATU (149 mg, 0.392 mmol). This was stirred overnight and was then purified by preparative HPLC (PHENOMENEX® Luna 5u C18 21.2×250 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 30 min, 15 mL/min, 220 nM, product retention=33.8 min) to give (R/S)-2-hydroxy-N-(2-hydroxyethyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (34 mg, 0.065 mmol, 21.3% yield): LCMS [M+H]+=475.1; 1H NMR (400 MHz, methanol-d4) δ ppm 8.16 (2 H, dd, J=8.35, 4.39 Hz), 7.64-7.77 (4 H, m), 7.47-7.64 (3 H, m), 5.10-5.21 (1 H, m), 4.46 (2 H, t, J=5.49 Hz), 3.55-3.69 (2 H, m), 3.37 (1 H, m). HPLC Peak RT=8.6 min (Analytical Method A).

Provenance & Evidence