Formic Acid → HCID 53495390, 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, 45 mg, 0.104 mmol), (S)-2-amino-3-methylbutanenitrile (Int-XIII), formic acid salt (15.04 mg, 0.104 mmol), 4-methylmorpholine (42.2 mg, 0.417 mmol), and HATU (51.6 mg, 0.136 mmol) were dissolved in DMF (1 mL). After stirring 1 h, this 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 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 30-100% 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 single enantiomer N—((S)-1-cyano-2-methylpropyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (3.8 mg, 0.007 mmol, 7.1% yield, and its purity was 100%): LCMS=512.1 [M+H]+; 1H NMR (500 MHz, methanol-d4) δ ppm 8.16 (2 H, d, J=8.32 Hz), 7.48-7.72 (7 H, m), 5.19 (1 H, s), 4.63 (1 H, d, J=7.49 Hz), 2.01-2.15 (1 H, m, J=13.80, 6.83, 6.83, 6.66 Hz), 1.07 (3 H, d, J=6.66 Hz), 0.95 (3 H, d, J=6.94 Hz); HPLC peak RT=3.0 min (Method E).

Provenance & Evidence