4-Methylmorpholine → HCID 53495247, compound

Participants

Reaction Steps

2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-Va, 30 mg, 0.070 mmol), 2-amino-2-methylpropanenitrile-HCl (12.58 mg, 0.104 mmol) [Ingate, S. T. et al., Tetrahedron, 53:17795-17814 (1997)], HATU (34.4 mg, 0.090 mmol), and 4-methylmorpholine (28.1 mg, 0.278 mmol) were dissolved in DMF (1 mL). After stirring 1 h, the mixture 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: 40-100% 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 provide single enantiomer N-(2-cyanopropan-2-yl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (3.7 mg, 0.007 mmol, 10.7% yield): LCMS=498.0 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.13-8.19 (2 H, m), 7.49-7.70 (7 H, m), 5.13 (1 H, s), 1.71 (3 H, s), 1.67 (3 H, s); HPLC peak RT=2.9 min (Method E).

Provenance & Evidence