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

(R/S)-2-Hydroxy-2-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-VII, 40 mg, 0.093 mmol), 1-amino-2-methylpropan-2-ol (12.43 mg, 0.139 mmol), 4-methylmorpholine (37.6 mg, 0.372 mmol), and HATU (45.9 mg, 0.121 mmol) were dissolved in DMF (1 mL). It was stirred for 20 min and was 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% methanol to 100% methanol over 10 min, 20 mL/min, 220 nM, product retention=11.2 min) to provide (R/S)-2-hydroxy-N-(2-hydroxy-2-methylpropyl)-2-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (20 mg, 0.036 mmol, 39.2% yield): LCMS=502.2 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.48 (1 H, s), 8.13 (2 H, d, J=8.35 Hz), 7.52-7.76 (7 H, m), 5.16 (1 H, s), 3.25 (2 H, s), 1.17 (3 H, s), 1.14 (3 H, s); HPLC peak RT=7.3 min (Method A).

1. customwas 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% methanol to 100% methanol over 10 min, 20 mL/min, 220 nM, product retention=11.2 min)

ORD 기록

ord-d54183e22a3148aa8915803a1b41ac99

출처 데이터셋

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08835470B2