Aluminum(III) Chloride → N-[3-(2,6-dichloro-4-cyanobenzoyl)-1H-pyrrolo[2,3-c]pyridin-7yl]cyclopropane carboxamide

HRID 2201839Notes

Reaction equation

HRID 2201839 reaction equation
[NH:1]1[C:5]2=[C:6]([NH:10][C:11]([CH:13]3[CH2:15][CH2:14]3)=[O:12])[N:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1.[Cl-].[Al+3].[Cl-].[Cl-].[Cl:20][C:21]1[CH:29]=[C:28]([C:30]#[N:31])[CH:27]=[C:26]([Cl:32])[C:22]=1[C:23](Cl)=[O:24]>CO>[Cl:20][C:21]1[CH:29]=[C:28]([C:30]#[N:31])[CH:27]=[C:26]([Cl:32])[C:22]=1[C:23]([C:3]1[C:4]2[C:5](=[C:6]([NH:10][C:11]([CH:13]3[CH2:14][CH2:15]3)=[O:12])[N:7]=[CH:8][CH:9]=2)[NH:1][CH:2]=1)=[O:24]

Participants

5

Reactant 3

HCID 6451240Aluminum(III) ChlorideHCID 71061452HCID 71061452, compoundHCID 866489562,6-Dichloro-4-cyanobenzoyl chloride

Product 1

HCID 71618373N-[3-(2,6-dichloro-4-cyanobenzoyl)-1H-pyrrolo[2,3-c]pyridin-7yl]cyclopropane carboxamideYield 38.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

N-(1H-pyrrolo[2,3-c]pyridin-7-yl)cyclopropanecarboxamide (1 g, 4.9 mmol) was added to a stirred suspension of aluminium chloride (3.30 g, 24.8 mmol) in dry dichloromehane (100 mL) and the mixture was stirred at room temperature for about 1 hour, followed by drop-wise addition of 2,6-dichloro-4-cyanobenzoyl chloride (1.16 g, 4.9 mmol). The resulting reaction mixture was stirred at room temperature for about 8 hours. Methanol (25 mL) was added cautiously to quench the reaction mass followed by concentration under vacuum. The resulting residue was taken up in water followed by partitioning with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel (100-200) column chromatography using ethyl acetate and hexane gradient elution to afford N-[3-(2,6-dichloro-4-cyanobenzoyl)-1H-pyrrolo[2,3-c]pyridin-7yl]cyclopropane carboxamide (0.75 g, 37.87%).

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature for about 8 hours
  3. customto quench the reaction mass
  4. concentrationfollowed by concentration under vacuum
  5. customby partitioning with ethyl acetate
  6. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by silica gel (100-200) column chromatography
  10. washethyl acetate and hexane gradient elution

Sources & evidence

ORD record
ord-cf3f579b4ee942bd9ac7561eaab769bb
Source dataset
uspto-grants-2016_06
Patent number
US09364466B2

Reaction notes

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