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

HRID 2352943Notes

Reaction equation

HRID 2352943 reaction equation
[Cl:1][C:2]1[C:3]([C:9]([OH:11])=O)=[N:4][N:5]([CH2:7][CH3:8])[CH:6]=1.S(Cl)(Cl)=O.[NH2:16][C:17]1[CH:18]=[C:19]([CH:32]=[CH:33][CH:34]=1)[C:20]([C:22]1[CH:30]=[C:29]2[C:25]([CH2:26][C:27](=[O:31])[NH:28]2)=[CH:24][CH:23]=1)=[O:21]>C1COCC1>[O:31]=[C:27]1[CH2:26][C:25]2[C:29](=[CH:30][C:22]([C:20]([C:19]3[CH:18]=[C:17]([NH:16][C:9]([C:3]4[C:2]([Cl:1])=[CH:6][N:5]([CH2:7][CH3:8])[N:4]=4)=[O:11])[CH:34]=[CH:33][CH:32]=3)=[O:21])=[CH:23][CH:24]=2)[NH:28]1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 5898204-Chloro-1-ethyl-1H-pyrazole-3-carboxylic acidHCID 592564786-(3-Amino-benzoyl)-1,3-dihydro-indol-2-one

Product 1

HCID 866104444-Chloro-1-ethyl-1H-pyrazole-3-carboxylic acid [3-(2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amideYield 54.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
79 °C

Procedure

A dry flask was charged with 4-Chloro-1-ethyl-1H-pyrazole-3-carboxylic acid (0.179 g, 1.03 mmol) and thionyl chloride (5 mL) and allowed to stir at 79° C. for 3 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 (10 mL). 6-(3-Amino-benzoyl)-1,3-dihydro-indol-2-one (as prepared in Example 40, 0.260 g, 1.03 mmol) was added to the THF solution of the acid chloride, and the mixture was allowed to reflux overnight. The reaction mixture was then allowed to cool to room temperature and subsequently vacuum filtered. The solid was washed with 0° C. THF (˜5 mL) and collected to afford the 4-Chloro-1-ethyl-1H-pyrazole-3-carboxylic acid [3-(2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide as a solid (0.227 g, 0.560 mmol, 54%).

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 (10 mL)
  4. temperatureto reflux overnight
  5. temperatureto cool to room temperature
  6. filtrationsubsequently vacuum filtered
  7. washThe solid was washed with 0° C
  8. customTHF (˜5 mL) and collected

Sources & evidence

ORD record
ord-da3a213b469c49d6b5f673f9ff039121
Source dataset
uspto-grants-2010_07
Patent number
US07749530B2

Reaction notes

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