Methanol → N-[3-(2,6-dichlorobenzoyl)-2-methyl-1H-pyrrolo[2,3-c]pyridin-7-yl]cyclopropanecarboxamide

HRID 2201849Notes

Reaction equation

HRID 2201849 reaction equation
[CH3:1][C:2]1[NH:16][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]=1.[Cl-].[Al+3].[Cl-].[Cl-].[Cl:21][C:22]1[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[C:23]=1[C:24](Cl)=[O:25].CO>ClCCl>[Cl:21][C:22]1[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[C:23]=1[C:24]([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:16][C:2]=1[CH3:1])=[O:25]

Participants

6

Reactant 4

HCID 887MethanolHCID 783922,6-Dichlorobenzoyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 71061496N-(2-methyl-1H-pyrrolo[2,3-c]pyridin-7-yl)cyclopropanecarboxamide

Product 1

HCID 86720653N-[3-(2,6-dichlorobenzoyl)-2-methyl-1H-pyrrolo[2,3-c]pyridin-7-yl]cyclopropanecarboxamideYield 39.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N-(2-Methyl-1H-pyrrolo[2,3-c]pyridin-7yl)cyclopropanecarboxamide (100 mg, 0.46 mmol) was added to a stirred suspension of aluminium chloride (620 mg, 4.65 mmol) in dry dichloromethane (5 mL) and the mixture was stirred at room temperature for about 1 hour under argon atmosphere. This was followed by drop wise addition of a solution of 2,6-dichlorobenzoyl chloride (194 mg, 0.93 mmol) in dichloromethane and stirring overnight at room temperature. After completion, methanol (10 mL) was added cautiously to quench the reaction mass followed by concentration under vacuum. The residual mass was diluted with water and extracted with ethyl acetate. The combined organic layer was neutralized using aq. sodium bicarbonate solution, washed with brine, dried over anhydrous sodium sulfate and concentrated. Purification by silica gel (100-200) column chromatography using dichloromethane and methanol gradient as eluent afforded N-[3-(2,6-dichlorobenzoyl)-2-methyl-1H-pyrrolo[2,3-c]pyridin-7-yl]cyclopropanecarboxamide (70 mg, 39%).

Workup

  1. stirringstirring overnight at room temperature
  2. customto quench the reaction mass
  3. concentrationfollowed by concentration under vacuum
  4. additionThe residual mass was diluted with water
  5. extractionextracted with ethyl acetate
  6. washwashed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customPurification by silica gel (100-200) column chromatography

Sources & evidence

ORD record
ord-14fecd2b81774413bc6f6726a60c558f
Source dataset
uspto-grants-2016_06
Patent number
US09364466B2

Reaction notes

Loading…