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

関与物質

反応手順

(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), (S)-(+)-1-amino-2-propanol (7.84 mg, 0.104 mmol), HATU (34.4 mg, 0.090 mmol), and 4-methylmorpholine (28.1 mg, 0.278 mmol) were dissolved in DMF (1 mL). After stirring 1 h, the 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=11.8 min) to provide 2-hydroxy-N—((S)-2-hydroxypropyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (19 mg, 0.031 mmol, 44.7% yield) as a mixture of diastereomers: LCMS=489.1 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.16 (2 H, d, J=8.35 Hz), 7.54-7.74 (7 H, m), 5.15 (1 H, s), 3.80-3.92 (1 H, m), 3.12-3.42 (2 H, m), 1.13 (3 H, d, J=4.83 Hz); HPLC peak RT=8.6 min (Method A).

情報源と証拠