Reaction #164361

Reaction equation

(R/S)-2-Hydroxy-2-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid

(S)-1-aminopropan-2-ol

HATU

4-methylmorpholine

HATU

→

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

Yield 44.1%

Solvents

DMF

Conditions

Workup

1. 1
   workup.ADDITIONwas added
2. 2
   Otherit 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 15 min, 20 mL/min, 220 nM, product retention 15.1 min)

Procedure

(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), (S)-1-aminopropan-2-ol (10.47 mg, 0.139 mmol), HATU (45.9 mg, 0.121 mmol), and 4-methylmorpholine (37.6 mg, 0.372 mmol) were added to DMF (1 mL). It was stirred for 20 min before additional HATU (35.3 mg, 0.093 mmol) was added. After stirring for an additional 10 min, it 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 15 min, 20 mL/min, 220 nM, product retention 15.1 min) to provide (R/S)-2-hydroxy-N-((S)-2-hydroxypropyl)-2-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (20 mg, 0.041 mmol, 43.8% yield) as a mixture of diastereomers: LCMS=488.1 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.46 (1 H, s), 8.12 (2 H, d, J=8.35 Hz), 7.52-7.72 (7 H, m), 5.14 (1 H, s), 3.78-3.94 (1 H, m), 3.13-3.34 (2 H, m), 1.13 (3 H, d, J=7.47 Hz); HPLC peak RT=7.0 min (Method A).

Source