Acetone → 6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazole-5-carbaldehyde

HRID 1676479Notes

Reaction equation

HRID 1676479 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([CH2:25][OH:26])=[CH:11][C:12]3[N:16]([CH2:17][CH2:18][S:19]([CH3:22])(=[O:21])=[O:20])[CH:15]=[N:14][C:13]=3[C:23]=2[F:24])=[C:4]([Cl:27])[CH:3]=1.CC(C)=O>C1COCC1.O=[Mn]=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([CH:25]=[O:26])=[CH:11][C:12]3[N:16]([CH2:17][CH2:18][S:19]([CH3:22])(=[O:21])=[O:20])[CH:15]=[N:14][C:13]=3[C:23]=2[F:24])=[C:4]([Cl:27])[CH:3]=1

Participants

5

Reactant 2

HCID 180AcetoneHCID 21114203[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazol-5-yl]-methanol

Product 1

HCID 211142046-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazole-5-carbaldehydeYield 82.3%

Reagents, catalysts & solvents 2

HCID 14801Manganese dioxideCatalyst2×HCID 8028TetrahydrofuranSolvent

Procedure

[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazol-5-yl]-methanol 10y (0.050, 0.105 mmol) is dissolved in 1:1 THF:acetone (2 mL) under N2 and MnO2 (0.046 g, 0.524 mmol) is added. The reaction mixture is stirred at room temperature for 16 hours, and then at 55° C. for 5 hours. Additional MnO2 (0.046 g, 0.524 mmol) is added and the reaction mixture stirred at 55° C. for 2 hours. The reaction mixture is concentrated to dryness and the residue dissolved in 10:1 methylene chloride:MeOH. The solution is filtered through a silica gel plug eluted with 10:1 methylene chloride:MeOH. The resulting filtrate is concentrated under reduced pressure to give 41 mg (82%) desired product as a bright yellow solid.

Workup

  1. waitat 55° C. for 5 hours
  2. stirringthe reaction mixture stirred at 55° C. for 2 hours
  3. concentrationThe reaction mixture is concentrated to dryness
  4. dissolutionthe residue dissolved in 10:1 methylene chloride
  5. filtrationThe solution is filtered through a silica gel plug
  6. washeluted with 10:1 methylene chloride
  7. concentrationThe resulting filtrate is concentrated under reduced pressure

Sources & evidence

ORD record
ord-50de8d3eb50b4df693445857ee516024
Source dataset
uspto-grants-2011_08
Patent number
US08003805B2

Reaction notes

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