4-Methylmorpholine → (R/S)-N-(3-(3,3-difluoroazetidin-1-yl)-3-oxopropyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide

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(R/S)-3-(2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamido)propanoic acid (Int-V, 25 mg, 0.050 mmol), 3,3-difluoroazetidine-HCl (6.45 mg, 0.050 mmol), 4-methylmorpholine (20.13 mg, 0.199 mmol), and HATU (24.60 mg, 0.065 mmol) were added to DMF (1 mL). This was stirred for 1 h before it was purified by prep HPLC (PHENOMENEX® Luna 5u 21.2×100 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 10 min, 20 mL/min, 220 nM, product retention=10.6 min) to provide (R/S)-N-(3-(3,3-difluoroazetidin-1-yl)-3-oxopropyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (5 mg, 6.53 μmol, 13.12% yield): LCMS=578.3 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.14-8.24 (2 H, m), 7.51-7.74 (7 H, m), 5.11 (1 H, s), 4.49 (2 H, td, J=11.77, 7.04 Hz), 4.29 (2 H, t, J=12.21 Hz), 3.45-3.58 (2 H, m), 2.38-2.52 (2 H, m); HPLC peak RT=9.4 min (Method A).

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