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

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, 20 mg, 0.046 mmol), cyclobutanamine (4.95 mg, 0.070 mmol), HATU (22.92 mg, 0.060 mmol), and 4-methylmorpholine (18.76 mg, 0.185 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 12 min, 20 mL/min, 220 nM, product retention=14.17 min) to provide (R/S)-N-cyclobutyl-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (7 mg, 0.011 mmol, 23.93% yield): LCMS=485.3 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.12-8.23 (2 H, m), 7.53-7.73 (7 H, m), 5.09 (1 H, s), 4.15-4.42 (1 H, m), 2.28 (2 H, dddd, J=10.07, 4.90, 4.62, 2.86 Hz), 1.98-2.13 (2 H, m), 1.70-1.79 (2 H, m); HPLC peak RT=10.4 min (Method A).

Provenance & Evidence