Thionyl Chloride → 3,5-dichloro-4-({7-[(cyclopropylcarbonyl)amino]-2-methyl-1H-pyrrolo[2,3-c]pyridin-3-yl}carbonyl)-N-methylbenzamide

HRID 2201851Notes

Reaction equation

HRID 2201851 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([C:11](=[O:14])[NH:12][CH3:13])[CH:8]=[C:7]([Cl:15])[C:3]=1[C:4]([OH:6])=O.S(Cl)(Cl)=O.[CH3:20][C:21]1[NH:35][C:24]2=[C:25]([NH:29][C:30]([CH:32]3[CH2:34][CH2:33]3)=[O:31])[N:26]=[CH:27][CH:28]=[C:23]2[CH:22]=1.[Cl-].[Al+3].[Cl-].[Cl-]>ClCCl.CO>[Cl:15][C:7]1[CH:8]=[C:9]([CH:10]=[C:2]([Cl:1])[C:3]=1[C:4]([C:22]1[C:23]2[C:24](=[C:25]([NH:29][C:30]([CH:32]3[CH2:33][CH2:34]3)=[O:31])[N:26]=[CH:27][CH:28]=2)[NH:35][C:21]=1[CH3:20])=[O:6])[C:11]([NH:12][CH3:13])=[O:14]

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 6451240Aluminum(III) ChlorideHCID 71061496N-(2-methyl-1H-pyrrolo[2,3-c]pyridin-7-yl)cyclopropanecarboxamideHCID 710616332,6-Dichloro-4-(methylcarbamoyl)benzoic acid

Product 1

HCID 867206553,5-dichloro-4-({7-[(cyclopropylcarbonyl)amino]-2-methyl-1H-pyrrolo[2,3-c]pyridin-3-yl}carbonyl)-N-methylbenzamideYield 29%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2,6-dichloro-4-(methylcarbamoyl)benzoic acid (276 mg, 1.1 mmol) in dry dichloromethane, was added thionyl chloride (5 mL) and heated at 100° C. for about 3 hours. The mixture was concentrated under vacuum. The residue was dissolved in dry dichloromethane (3 mL) and added to the stirred solution of N-(2-methyl-1H-pyrrolo[2,3-c]pyridin-7-yl)cyclopropanecarboxamide (120 mg, 0.55 mmol) in aluminium chloride (743 mg, 5.57 mmol) drop wise. The resulting reaction mixture was stirred overnight at room temperature. After completion, methanol (10 mL) was added cautiously to quench the reaction mass followed by concentration under vacuum. The reaction mass was diluted with water and extracted with ethyl acetate. The combined organic layer was washed with aq. sodium bicarbonate solution, brine, dried over anhydrous sodium sulfate, and concentrated. Purification by silica gel (100-200) column chromatography using dichloromethane and methanol gradient as eluent afforded 3,5-dichloro-4-({7-[(cyclopropylcarbonyl)amino]-2-methyl-1H-pyrrolo[2,3-c]pyridin-3-yl}carbonyl)-N-methylbenzamide (70 mg, 29%).

Workup

  1. concentrationThe mixture was concentrated under vacuum
  2. dissolutionThe residue was dissolved in dry dichloromethane (3 mL)
  3. customThe resulting reaction mixture
  4. customto quench the reaction mass
  5. concentrationfollowed by concentration under vacuum
  6. additionThe reaction mass was diluted with water
  7. extractionextracted with ethyl acetate
  8. washThe combined organic layer was washed with aq. sodium bicarbonate solution, brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated
  11. customPurification by silica gel (100-200) column chromatography

Sources & evidence

ORD record
ord-609cf58181dd415d82ec439299a55f7a
Source dataset
uspto-grants-2016_06
Patent number
US09364466B2

Reaction notes

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