4-Methylmorpholine → HCID 53495246, compound

Participants

Reaction Steps

Single enantiomer 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), (R/S)-2-aminopropane-1,3-diol (9.51 mg, 0.104 mmol), 4-methylmorpholine (28.1 mg, 0.278 mmol), and HATU (34.4 mg, 0.090 mmol) were dissolved in DMF (1 mL). After stirring 1 h, the reaction mixture 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=11.33 min) to provide the product N-(1,3-dihydroxypropan-2-yl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide as a mixture of diastereomers (13 mg, 0.023 mmol, 32.6% yield): LCMS=505.1 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.12-8.27 (2 H, m), 7.92-8.01 (1 H, m), 7.50-7.81 (7 H, m), 5.16 (1 H, s), 3.95 (1 H, dt, J=8.53, 5.42 Hz), 3.55-3.79 (4 H, m); HPLC peak RT=8.3 min (Method A).

Provenance & Evidence