Dimethylformamide → 3-(2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamido)-N,N-dimethylpropanamide

Participants

Reaction Steps

(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 (Example 22, 22 mg, 0.044 mmol), dimethylamine-HCl (5.36 mg, 0.066 mmol), 4-methylmorpholine (17.72 mg, 0.175 mmol), and HATU (21.65 mg, 0.057 mmol) were added to DMF (1 mL). This was stirred for 1 h and then 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=13.4 min) to provide (R/S)-3-(2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamido)-N,N-dimethylpropanamide (9 mg, 0.016 mmol, 36.4% yield): LCMS=530.3 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.14-8.19 (2 H, m), 7.55-7.71 (7 H, m), 5.11 (1 H, s), 3.51 (2 H, t, J=6.60 Hz), 2.98 (3 H, s), 2.92 (3 H, s), 2.60 (2 H, t, J=6.49 Hz); HPLC peak RT=8.8 min (Method A).

Provenance & Evidence