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

HRID 2352846Notes

Reaction equation

HRID 2352846 reaction equation
[CH3:1][N:2]1[C:6]([C:7]([OH:9])=O)=[CH:5][C:4]([CH3:10])=[N:3]1.S(Cl)(Cl)=O.[NH2:15][C:16]1[CH:17]=[C:18]([CH:31]=[CH:32][CH:33]=1)[C:19]([C:21]1[CH:29]=[C:28]2[C:24]([CH2:25][C:26](=[O:30])[NH:27]2)=[CH:23][CH:22]=1)=[O:20]>C1COCC1>[O:30]=[C:26]1[CH2:25][C:24]2[C:28](=[CH:29][C:21]([C:19]([C:18]3[CH:17]=[C:16]([NH:15][C:7]([C:6]4[N:2]([CH3:1])[N:3]=[C:4]([CH3:10])[CH:5]=4)=[O:9])[CH:33]=[CH:32][CH:31]=3)=[O:20])=[CH:22][CH:23]=2)[NH:27]1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 5877211,3-Dimethyl-1H-pyrazole-5-carboxylic acidHCID 592564786-(3-Amino-benzoyl)-1,3-dihydro-indol-2-one

Product 1

HCID 866103932,5-Dimethyl-2H-pyrazole-3-carboxylic acid [3-(2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amideYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
79 °C

Procedure

A dry 250 mL flask was charged with 2,5-Dimethyl-2H-pyrazole-3-carboxylic acid (0.989 g, 7.057 mmol) and thionyl chloride (5 mL) and allowed to stir at 79° C. for 2 h. The thionyl chloride was then removed by concentration in vacuo. The crude acid chloride was cooled to room temperature, and then dissolved in THF (40 mL). 6-(3-Amino-benzoyl)-1,3-dihydro-indol-2-one (as prepared in Example 40, 1.26 g, 4.994 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. The solid residue was suspended in boiling EtOAc. The suspension was allowed to cool to room temperature before filtering to afford the 2,5-Dimethyl-2H-pyrazole-3-carboxylic acid [3-(2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide as a tan solid (1.4 g, 3.74 mmol, 75%).

Workup

  1. customThe thionyl chloride was then removed by concentration in vacuo
  2. temperatureThe crude acid chloride was cooled to room temperature
  3. dissolutiondissolved in THF (40 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. temperatureto cool to room temperature
  9. filtrationbefore filtering

Sources & evidence

ORD record
ord-79c788d6d70a4c0ea6c4944e61308d8e
Source dataset
uspto-grants-2010_07
Patent number
US07749530B2

Reaction notes

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