4-Methylmorpholine → HCID 53496994, 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, 0.07 mmol) was dissolved in DMF (1 mL) prior to the addition of 4-methylmorpholine (38.2 μL, 0.348 mmol), (S)-tetrahydrofuran-3-amine-HCl (15.47 mg, 0.125 mmol), and BOP (55.4 mg, 0.125 mmol). The reaction mixture was stirred overnight and was then 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: 50-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow rate=20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to give (R/S)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)-N-((S)-tetrahydrofuran-3-yl)acetamide (12.9 mg, 0.026 mmol, 37.1% yield): LCMS=501.1 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.05-8.24 (4 H, m), 7.48-7.79 (14 H, m), 5.00-5.21 (2 H, m), 4.35-4.47 (2 H, m), 3.91-3.99 (2 H, m), 3.74-3.91 (4 H, m), 3.57-3.70 (2 H, m), 2.13-2.33 (2 H, m), 1.80-1.98 (2 H, m); Analytical LCMS: column: Mac-mod Halo C18, 4.6×50 mm, 2.7-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 0.05% TFA; Mobile Phase B: 90:10 acetonitrile:water with 0.05% TFA; Temperature: 45° C.; Gradient: 0-100% B over 4 minutes, flow rate=4 mL/min, product retention=2.4 min (mixture of diastereomers).

Provenance & Evidence