反応 #607858

反応方程式

4-(4-amino-3-chlorophenoxy)picolinamide

1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid

1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid

EDCI

EDCI

HOAT

→

title compound

収率 46.5%

4-(3-chloro-4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)phenoxy)picolinamide

収率 46.5%

溶媒

water

DCM

反応条件

後処理

1. 1
   workup.STIRRINGThe mixture was further stirred at 46° C. for 13 hours
2. 2
   温度cooled to rt
3. 3
   抽出The resulted mixture was extracted with ethyl acetate (10 mL×3)
4. 4
   洗浄the combined organic phases were washed with brine (10 mL)
5. 5
   乾燥dried over anhydrous Na2SO4
6. 6
   濃縮concentrated in vacuo
7. 7
   その他The residue was purified by a silica gel column chromatography (DCM/MeOH (v/v)=50/1)

実験手順

To a suspension of 4-(4-amino-3-chlorophenoxy)picolinamide (191 mg, 0.72 mmol) and 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (168 mg, 0.72 mmol) in DCM (10 mL) was added EDCI (166 mg, 0.86 mmol) and HOAT (20 mg, 0.14 mmol). The reaction was stirred at 46° C. for 6 hours, followed by the addition of 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (32 mg, 0.14 mmol) and EDCI (27 mg, 0.14 mmol). The mixture was further stirred at 46° C. for 13 hours, then cooled to rt and diluted with water (10 mL). The resulted mixture was extracted with ethyl acetate (10 mL×3), and the combined organic phases were washed with brine (10 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (DCM/MeOH (v/v)=50/1) to give the title compound as a pale yellow solid (160 mg, 46.5%).

出典