تفاعل #45015

معادلة التفاعل

Oxalyl chloride

4-fluorobenzoic acid

DIPEA

5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine

→

title compound

المردود 3.0%

N-[5-[2-(3,5-Dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]-4-fluoro-benzamide

المردود 3.0%

المذيبات

dichloromethane

DCM

DCM

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONwas added dropwise over 15 mins
2. 2
   درجة الحرارةto warm to room temperature overnight
3. 3
   غسيلwashed with aqueous NaHCO3 solution (50 ml)
4. 4
   استخلاصThe aqueous layer was extracted with DCM (50 ml)
5. 5
   أخرىThe combined organic layers were collected
6. 6
   تركيزconcentrated
7. 7
   أخرىThe crude product was purified by reverse-phase prep HPLC
8. 8
   أخرىThe desired fractions were evaporated

الإجراء التجريبي

Oxalyl chloride (2M in DCM, 1.40 ml, 2.75 mmol, 1.1 eq) was added dropwise to a mixture of 4-fluorobenzoic acid (350 mg, 2.50 mmol, 1 eq) in dichloromethane (15 ml) at 0° C. containing a few drops of DMF (10 ul, 0.12 mmol, 0.05 eq) and DIPEA (937 μl, 5.25 mmol, 2.1 eq). After stirring for 60 mins at 0° C. a solution of 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (742 mg, 3 mmol, 1.2 eq) in DCM (10 ml) was added dropwise over 15 mins. The mixture was maintained at 0° C. for a further 2 h, then gradually allowed to warm to room temperature overnight. The mixture was diluted with DCM (50 ml) and washed with aqueous NaHCO3 solution (50 ml). The aqueous layer was extracted with DCM (50 ml). The combined organic layers were collected and concentrated. The crude product was purified by reverse-phase prep HPLC using a 30-50% gradient of acetonitrile in water containing 1% ammonium hydroxide solution. The desired fractions were evaporated to afford the title compound as a beige solid. (31.5 mg, 3% yield)

المصدر