4-Methylmorpholine → HCID 178430881, compound

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), C-(4-methyl-1H-imidazol-2-yl)-methylamine hydrochloride (5.15 mg, 0.046 mmol), 4-methylmorpholine (18.76 mg, 0.185 mmol), and HATU (22.92 mg, 0.060 mmol) were dissolved in 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: 45-100% 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-((4-methyl-1H-imidazol-2-yl)methyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (5.5 mg, 10.07 μmol, 21.71% yield): LCMS=525.2 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.15 (2 H, d, J=8.53 Hz), 7.48-7.72 (8 H, m), 6.64 (1 H, d, J=1.00 Hz), 5.17 (1 H, s), 4.28-4.53 (2 H, m), 2.18 (3H, d, J=1.00 Hz); HPLC peak RT=2.5 min (Method E).

Provenance & Evidence