Thionyl Chloride → 2-Ethyl-5-methyl-2H-pyrazole-3-carboxylic acid [4-(2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide

HRID 640848Notes

Reaction equation

HRID 640848 reaction equation
[CH2:1]([N:3]1[C:7]([C:8]([OH:10])=O)=[CH:6][C:5]([CH3:11])=[N:4]1)[CH3:2].S(Cl)(Cl)=O.[NH2:16][C:17]1[CH:34]=[CH:33][C:20]([C:21]([C:23]2[CH:31]=[C:30]3[C:26]([CH2:27][C:28](=[O:32])[NH:29]3)=[CH:25][CH:24]=2)=[O:22])=[CH:19][CH:18]=1>C1COCC1>[O:32]=[C:28]1[CH2:27][C:26]2[C:30](=[CH:31][C:23]([C:21]([C:20]3[CH:19]=[CH:18][C:17]([NH:16][C:8]([C:7]4[N:3]([CH2:1][CH3:2])[N:4]=[C:5]([CH3:11])[CH:6]=4)=[O:10])=[CH:34][CH:33]=3)=[O:22])=[CH:24][CH:25]=2)[NH:29]1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 27437941-Ethyl-3-methyl-1H-pyrazole-5-carboxylic acidHCID 592564856-(4-Amino-benzoyl)-1,3-dihydro-indol-2-one

Product 1

HCID 866103782-Ethyl-5-methyl-2H-pyrazole-3-carboxylic acid [4-(2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amideYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
79 °C

Procedure

A dry 25 mL flask was charged with 2-Ethyl-5-methyl-2H-pyrazole-3-carboxylic acid (0.887 g, 5.16 mmol) and thionyl chloride (5 mL) and allowed to stir at 79° C. for 2 h. The thionyl chloride then was removed by concentration in vacuo. The crude acid chloride was cooled to room temperature, and then dissolved in THF (5 mL). 6-(4-Amino-benzoyl)-1,3-dihydro-indol-2-one (1.00 g, 3.97 mmol) was added to the THF solution of the acid chloride, and the mixture was allowed to reflux for 4 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 precipitate. The solids were filtered to afford the pure 2-Ethyl-5-methyl-2H-pyrazole-3-carboxylic acid [4-(2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide (0.741 g, 1.94 mmol, 49%).

Workup

  1. customThe thionyl chloride then was removed by concentration in vacuo
  2. temperatureThe crude acid chloride was cooled to room temperature
  3. dissolutiondissolved in THF (5 mL)
  4. temperatureto reflux for 4 h
  5. temperatureto cool to room temperature
  6. customThe room temperature reaction mixture
  7. concentrationwas concentrated in vacuo
  8. dissolutionthe crude residue was dissolved in EtOH (5 mL)
  9. additionThe ethanolic solution was treated with 1M NaOH(aq) (2 mL)
  10. stirringstirred for 30 min
  11. customyielding a precipitate
  12. filtrationThe solids were filtered

Sources & evidence

ORD record
ord-bb78766553d54f0da40541234f939e8e
Source dataset
uspto-grants-2010_04
Patent number
US07692005B2

Reaction notes

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