p-Toluenesulfonic acid → 5-bromo-2-chloro-3-(1-(2,3-dichlorophenyl)-1H-imidazol-2-yl)pyridine

HRID 1518512Notes

Reaction equation

HRID 1518512 reaction equation
CO[CH:3](OC)[CH2:4][NH2:5].[Br:8][C:9]1[CH:10]=[C:11]([C:16](Cl)=[N:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[C:19]=2[Cl:25])[C:12]([Cl:15])=[N:13][CH:14]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCCC1>[Br:8][C:9]1[CH:10]=[C:11]([C:16]2[N:17]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[C:19]=3[Cl:25])[CH:3]=[CH:4][N:5]=2)[C:12]([Cl:15])=[N:13][CH:14]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 89728Aminoacetaldehyde dimethyl acetalHCID 86616060N-((5-bromo-2-chloropyridin-3-yl)chloromethylene)-2,3-dichlorobenzenamine

Product 1

HCID 581798675-bromo-2-chloro-3-(1-(2,3-dichlorophenyl)-1H-imidazol-2-yl)pyridineYield 90.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2,2-dimethoxyethanamine (0.053 g, 0.505 mmol) in anhydrous tetrahydrofuran (5 mL) at 0-5° C. was added the N-((5-bromo-2-chloropyridin-3-yl)chloromethylene)-2,3-dichlorobenzenamine (0.1 g, 0.2526 mmol) as a solution in anhydrous tetrahydrofuran (5 mL). After stirring overnight, p-toluene sulfonic acid (0.05 g, 0.51 mmol) was added and the reaction mixture was stirred an additional 2 hours. After concentration to dryness the resulting solid purified by flash chromatography (0 to 30% ethyl acetate/methylene chloride) to provide 0.092 g of 5-bromo-2-chloro-3-(1-(2,3-dichlorophenyl)-1H-imidazol-2-yl)pyridine. Using the same procedure, 5-bromo-2-chloro-3-(1-(2,3-difluorophenyl)-1H-imidazol-2-yl)pyridine and 5-bromo-2-chloro-3-(1-(3-chloro-2-fluorophenyl)-1H-imidazol-2-yl)pyridine can be produced from 5-bromo-2-chloro-N-(2,3-difluorophenyl)pyridine-3-carboxamide and 5-bromo-2-chloro-N-(3-chloro-2-fluorophenyl)pyridine-3-carboxamide, respectively.

Workup

  1. stirringthe reaction mixture was stirred an additional 2 hours
  2. concentrationAfter concentration to dryness the resulting solid
  3. custompurified by flash chromatography (0 to 30% ethyl acetate/methylene chloride)

Sources & evidence

ORD record
ord-447a1564b75d4d83a42be8309bb66643
Source dataset
uspto-grants-2012_07
Patent number
US08232406B2

Reaction notes

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