N-bromobutanimide → Methyl 6-((4-bromo-2-chlorophenyl)amino)-7-fluoro-1H-benzo[d]imidazole-5-carboxylate

HRID 31979Notes

Reaction equation

HRID 31979 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[Cl:21])=[C:12]([F:22])[C:8]2[N:9]=[CH:10][NH:11][C:7]=2[CH:6]=1)=[O:4].CC1C=CC(S(O)(=O)=O)=CC=1.O.C1C(=O)N([Br:42])C(=O)C1>C1COCC1.CO>[CH3:1][O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([Br:42])=[CH:17][C:16]=2[Cl:21])=[C:12]([F:22])[C:8]2[N:9]=[CH:10][NH:11][C:7]=2[CH:6]=1)=[O:4]

Participants

5

Reactant 3

HCID 67184N-bromobutanimideHCID 521998p-Toluenesulfonic acid monohydrateHCID 668977516-(2-Chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester

Product 1

HCID 11749905Methyl 6-((4-bromo-2-chlorophenyl)amino)-7-fluoro-1H-benzo[d]imidazole-5-carboxylateYield 85%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

6-(2-Chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5carboxylic acid methyl ester 7b (55 mg, 0.172 mmol) is dissolved in 1:1 THF/MeOH (2 mL) and cooled to −780C under an atmosphere of nitrogen. TsOH.H2O (49 mg, 0.258 mmol) is added followed by NBS (31 mg, 0.174 mmol). After 10 minutes, the reaction mixture is warmed to 0° C. and then 2 hours later warmed to room temperature. After 16 hours, the reaction mixture is quenched by the addition of 10% Na2S2O3 and diluted with ethyl acetate and water. The layers are separated and the aqueous layer is extracted with ethyl acetate. The combined organic extracts are dried (MgSO4) and concentrated under reduced pressure. The crude product is triturated with methylene chloride to give 58 mg (85%) of pure desired product as a tan solid.

Workup

  1. temperaturecooled to −780C under an atmosphere of nitrogen
  2. temperature2 hours later warmed to room temperature
  3. waitAfter 16 hours
  4. customthe reaction mixture is quenched by the addition of 10% Na2S2O3
  5. additiondiluted with ethyl acetate and water
  6. customThe layers are separated
  7. extractionthe aqueous layer is extracted with ethyl acetate
  8. dry with materialThe combined organic extracts are dried (MgSO4)
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product is triturated with methylene chloride

Sources & evidence

ORD record
ord-4b19379b0921461499db9520ebc56115
Source dataset
uspto-grants-2008_09
Patent number
US07425637B2

Reaction notes

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