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

HRID 2352780Notes

Reaction equation

HRID 2352780 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:33]=[CH:32][C:20]([CH2:21][C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][CH:30]=2)[NH:27][C:26](=[O:31])[CH2:25]3)=[CH:19][CH:18]=1>C1COCC1>[O:31]=[C:26]1[CH2:25][C:24]2[C:28](=[CH:29][CH:30]=[C:22]([CH2:21][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:33][CH:32]=3)[CH:23]=2)[NH:27]1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 27437941-Ethyl-3-methyl-1H-pyrazole-5-carboxylic acidHCID 686983145-(4-Amino-benzyl)-1,3-dihydro-indol-2-one

Product 1

HCID 866103752-Ethyl-5-methyl-2H-pyrazole-3-carboxylic acid [4-(2-oxo-2,3-dihydro-1H-indol-5-ylmethyl)-phenyl]-amideYield 44.9%

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 (0.168 g, 1.09 mmol) and thionyl chloride (4 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 65° C., and then dissolved in THF (5 mL). 5-(4-Amino-benzyl)-1,3-dihydro-indol-2-one (0.200 g, 0.840 mmol) was added to the THF solution of the acid chloride, and the mixture was allowed to reflux overnight. Subsequently, the reaction mixture was 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 pale yellow precipitate. The pale yellow solids were filtered to afford the pure product (0.141 g, 0.377 mmol, 34.5%).

Workup

  1. customThe thionyl chloride was then removed by distillation
  2. temperatureThe crude acid chloride was cooled to 65° C.
  3. dissolutiondissolved in THF (5 mL)
  4. temperatureto reflux overnight
  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 pale yellow precipitate
  12. filtrationThe pale yellow solids were filtered

Sources & evidence

ORD record
ord-8be2d08e89b74031b100a7fc4358bfca
Source dataset
uspto-grants-2010_07
Patent number
US07749530B2

Reaction notes

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