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

Participants

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, 20 mg, 0.046 mmol), oxazol-2-ylmethanamine (6.82 mg, 0.070 mmol), 4-methylmorpholine (18.76 mg, 0.185 mmol), and HATU (22.92 mg, 0.060 mmol) were added to DMF (1 mL). This was stirred for 1 h before it was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×250 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: 5:95 methanol:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 methanol:water with 10-mM ammonium acetate; Gradient: 35-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to give (R/S)-2-hydroxy-N-(oxazol-2-ylmethyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (3.7 mg, 7.23 μmol, 15.60% yield): LCMS=512.1 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.16 (2 H, d, J=8.28 Hz), 7.50-7.83 (9 H, m), 7.09 (1 H, s), 5.20 (1 H, s), 4.45-4.67 (2 H, m); HPLC peak RT=2.6 min (Method E).

Provenance & Evidence