Dimethylformamide → (R/S)-N-(3-(1H-imidazol-1-yl)propyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide TFA

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, 0.070 mmol) was dissolved in DMF (1 mL) prior to the addition of 4-methylmorpholine (0.061 mL, 0.556 mmol), 1-(3-aminopropyl)imidazole (9.96 μL, 0.083 mmol), and HATU (39.7 mg, 0.104 mmol). The reaction mixture was stirred overnight and was then purified by preparative HPLC (PHENOMENEX® Luna 5u C18 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 time=10.6 min) to give (R/S)-N-(3-(1H-imidazol-1-yl)propyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide-TFA (10 mg, 0.014 mmol, 19.61% yield): LCMS=539.2 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.90 (1 H, s), 8.52 (1 H, t, J=6.15 Hz), 8.19 (2 H, d, J=8.35 Hz), 7.47-7.80 (9 H, m), 5.16 (1 H, s), 4.23 (2 H, td, J=6.81, 3.52 Hz), 3.22-3.29 (2 H, m), 2.12 (2 H, dq, J=6.81, 6.66 Hz). HPLC Peak RT=6.3 min (Analytical Method A).

Provenance & Evidence