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

HRID 640875Notes

Reaction equation

HRID 640875 reaction equation
[C:1]([C:4]1[S:8][C:7]([C:9]([OH:11])=O)=[CH:6][CH:5]=1)(=[O:3])[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:9]([C:7]4[S:8][C:4]([C:1](=[O:3])[CH3:2])=[CH:5][CH:6]=4)=[O:11])=[CH:34][CH:33]=3)=[O:22])=[CH:24][CH:25]=2)[NH:29]1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 37427275-Acetylthiophene-2-carboxylic acidHCID 592564856-(4-Amino-benzoyl)-1,3-dihydro-indol-2-one

Product 1

HCID 866103855-Acetyl-thiophene-2-carboxylic acid [4-(2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amideYield 99.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
79 °C

Procedure

A dry 100 mL flask was charged with 5-Acetyl-thiophene-2-carboxylic acid (0.9339 g, 5.49 mmol) and thionyl chloride (6 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 (80 mL). 6-(4-Amino-benzoyl)-1,3-dihydro-indol-2-one (as prepared in Example 15, 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. The solid residue was suspended in boiling EtOAc. The suspension was allowed to cool to room temperature before filtering to afford the 5-Acetyl-thiophene-2-carboxylic acid [4-(2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide as a solid (1.16 g, 3.94 mmol, 99%).

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 (80 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-1d90cb107bf440dd9bbf3a12f6fd9266
Source dataset
uspto-grants-2010_04
Patent number
US07692005B2

Reaction notes

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