Dimethyl Sulfone → 1-[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazol-5-yl]-2-methanesulfonyl-ethanone

HRID 1176908Notes

Reaction equation

HRID 1176908 reaction equation
[CH3:1][S:2]([CH3:5])(=[O:4])=[O:3].[Li]CCCC.CN(P(N(C)C)(N(C)C)=O)C.[Br:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:30]2[C:31]([CH:40]=[O:41])=[CH:32][C:33]3[NH:37][CH:36]=[N:35][C:34]=3[C:38]=2[F:39])=[C:25]([Cl:42])[CH:24]=1>C1COCC1>[Br:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:30]2[C:31]([C:40](=[O:41])[CH2:1][S:2]([CH3:5])(=[O:4])=[O:3])=[CH:32][C:33]3[NH:37][CH:36]=[N:35][C:34]=3[C:38]=2[F:39])=[C:25]([Cl:42])[CH:24]=1

Participants

6

Reactant 4

HCID 6213Dimethyl SulfoneHCID 12679HexamethylphosphoramideHCID 112456086-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehydeHCID 178418339Butyllithium

Product 1

HCID 112826131-[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazol-5-yl]-2-methanesulfonyl-ethanoneYield 97.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of methyl sulfone (65 mg, 0.68 mmol) in THF (1.5 mL) is added a solution of n-BuLi (0.27 mL, 0.68 mmol, 2.5 M solution in hexane) at −78° C. After stirring for 5 minutes, HMPA (0.1 mL) is added. After stirring for additional 10 minutes, a solution of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehyde 10f (26 mg, 0.069 mmol) in THF (1 mL) is added. The resulting solution is stirred for 1.5 hours at −78° C. The reaction is quenched with saturated aqueous NH4Cl, warmed to room temperature, and diluted with EtOAc. The organic layer is washed with water, dried over MgSO4, filtered, concentrated in vacuo, and purified by flash chromatography (3% MeOH in CH2Cl2) to give the crude desired product (31 mg, 96%) which is used directly without further purification: MS APCI (+) m/z 462, 464 (M+, Br pattern) detected.

Workup

  1. stirringAfter stirring for additional 10 minutes
  2. stirringThe resulting solution is stirred for 1.5 hours at −78° C
  3. customThe reaction is quenched with saturated aqueous NH4Cl
  4. additiondiluted with EtOAc
  5. washThe organic layer is washed with water
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. custompurified by flash chromatography (3% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-98e148b60998441087148d19cac37379
Source dataset
uspto-grants-2010_11
Patent number
US07842816B2

Reaction notes

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