Reaction #2439949

Reaction equation

2-Ethyl-5-methyl-2H-pyrazole-3-carboxylic acid

thionyl chloride

5-(4-Amino-benzoyl)-1,3-dihydro-indol-2-one

→

2-Ethyl-5-methyl-2H-pyrazole-3-carboxylic acid [4-(2-oxo-2,3-dihydro-1H-indole-5-carbonyl)-phenyl]-amide

Yield 72.1%

Solvents

THF

Conditions

Workup

1. 1
   OtherThe thionyl chloride was then removed by distillation
2. 2
   TemperatureThe crude acid chloride was cooled to room temperature
3. 3
   workup.DISSOLUTIONdissolved in THF (5 mL)
4. 4
   Temperatureto reflux for 2 h
5. 5
   Temperatureto cool to room temperature
6. 6
   OtherThe room temperature reaction mixture
7. 7
   Concentrationwas concentrated in vacuo
8. 8
   workup.DISSOLUTIONthe crude residue was dissolved in EtOH (5 mL)
9. 9
   workup.ADDITIONThe ethanolic solution was treated with 1M NaOH(aq) (2 mL)
10. 10
    workup.STIRRINGstirred for 30 min
11. 11
    Otheryielding a tan precipitate
12. 12
    FiltrationThe tan solids were filtered

Procedure

A dry 25 mL flask was charged with 2-Ethyl-5-methyl-2H-pyrazole-3-carboxylic acid (0.608 mg, 3.53 mmol) and thionyl chloride (10 mL) and allowed to stir at 79° C. for 2 h. The thionyl chloride was then removed by distillation. The crude acid chloride was cooled to room temperature, and then dissolved in THF (5 mL). 5-(4-Amino-benzoyl)-1,3-dihydro-indol-2-one (0.685 g, 2.72 mmol) was added to the THF solution of the acid chloride, and the mixture was allowed to reflux for 2 h. The reaction mixture was then allowed to cool to room temperature. The room temperature reaction mixture was concentrated in vacuo, and the crude residue was dissolved in EtOH (5 mL). The ethanolic solution was treated with 1M NaOH(aq) (2 mL) and stirred for 30 min. The basic solution was acidified to a pH of 1 with 1M HCl(aq) yielding a tan precipitate. The tan solids were filtered to afford pure 2-Ethyl-5-methyl-2H-pyrazole-3-carboxylic acid [4-(2-oxo-2,3-dihydro-1H-indole-5-carbonyl)-phenyl]-amide (0.760 g, 1.96 mmol, 72%).

Source