4-Methylmorpholine → HCID 53496225, 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, 30 mg, 0.070 mmol), 5-(aminomethyl)-2-methylpyrimidin-4-amine-2HCl (22.02 mg, 0.104 mmol), 4-methylmorpholine (28.1 mg, 0.278 mmol), and HATU (34.4 mg, 0.090 mmol) were added to DMF (1 mL). This was stirred for 1 h before it was purified via preparative LCMS 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)-N-((4-amino-2-methylpyrimidin-5-yl)methyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (17.5 mg, 0.032 mmol, 45.6% yield): LCMS=552.1 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.14 (2 H, d, J=8.53 Hz), 7.93 (1 H, s), 7.50-7.70 (7 H, m), 5.15 (1 H, s), 4.25 (2 H, d, J=4.02 Hz), 2.40 (3 H, s); HPLC peak RT=2.4 min (Method E).

Provenance & Evidence