Potassium Carbonate → 6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazole-5-carboxylic acid methyl ester

HRID 216462Notes

Reaction equation

HRID 216462 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=2[Cl:22])=[C:12]([F:23])[C:8]2[N:9]=[CH:10][NH:11][C:7]=2[CH:6]=1)=[O:4].C([O-])([O-])=O.[K+].[K+].[CH:30]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH2:31]>CN(C=O)C.C(OCC)(=O)C.O>[CH3:1][O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=2[Cl:22])=[C:12]([F:23])[C:8]2[N:9]=[CH:10][N:11]([CH2:31][CH2:30][S:32]([CH3:35])(=[O:34])=[O:33])[C:7]=2[CH:6]=1)=[O:4]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 19354Methyl vinyl sulfoneHCID 11749905Methyl 6-((4-bromo-2-chlorophenyl)amino)-7-fluoro-1H-benzo[d]imidazole-5-carboxylate

Product 1

HCID 672515916-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazole-5-carboxylic acid methyl esterYield 59.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester 8b (1.55 g, 3.89 mmol) is dissolved in 15 mL DMF under N2. K2CO3 (0.70 g, 5.06 mmol) is added followed by methyl vinyl sulfone (0.41 mL, 4.67 mmol). After stirring 16 hours at room temperature, the reaction mixture is diluted with ethyl acetate and water. The layers are separated and the organic layer is washed with water (3×) and brine. The combined aqueous washes are extracted with ethyl acetate. The combined organic extracts are dried (MgSO4) and concentrated under reduced. Purification by dissolving the residue in methylene chloride and precipitating with diethyl ether, repeated several times, provides 1.16 g (59%) pure desired product as a yellow solid: MS APCI (+) m/z 506, 504 (M+ Br pattern) and 400, 398 (M-methyl ethyl sulfone Br pattern).

Workup

  1. customThe layers are separated
  2. washthe organic layer is washed with water (3×) and brine
  3. extractionThe combined aqueous washes are extracted with ethyl acetate
  4. dry with materialThe combined organic extracts are dried (MgSO4)
  5. concentrationconcentrated under reduced
  6. customPurification
  7. dissolutionby dissolving the residue in methylene chloride
  8. customprecipitating with diethyl ether

Sources & evidence

ORD record
ord-f8a58cb81d0140b291d7d261bf6d8356
Source dataset
uspto-grants-2012_06
Patent number
US08193229B2

Reaction notes

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