Potassium Carbonate → (4-Bromo-2-chloro-phenyl)-(4-fluoro-6-oxazol-5-yl-1H-benzoimidazol-5-yl)-amine

HRID 2104060Notes

Reaction equation

HRID 2104060 reaction equation
[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.C([O-])([O-])=O.[K+].[K+].S([CH2:44][N+:45]#[C-:46])(C1C=CC(C)=CC=1)(=O)=O>CO>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:25]3[O:26][CH:46]=[N:45][CH:44]=3)=[CH:11][C:12]3[NH:16][CH:15]=[N:14][C:13]=3[C:23]=2[F:24])=[C:4]([Cl:27])[CH:3]=1.[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:25]3[O:26][CH:46]=[N:45][CH:44]=3)=[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

6

Reactant 3

HCID 11430Potassium CarbonateHCID 161915Tosylmethyl isocyanide2×HCID 211142046-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazole-5-carbaldehyde

Product 2

HCID 11452548(4-Bromo-2-chloro-phenyl)-(4-fluoro-6-oxazol-5-yl-1H-benzoimidazol-5-yl)-amineYield 18%HCID 21114189(4-bromo-2-chloro-phenyl)-[4-fluoro-1-(2-methanesulfonyl-ethyl)-6-oxazol-5-yl-1H-benzoimidazol-5-yl]-amineYield 4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazole-5-carbaldehyde 10z (0.025 g, 0.053 mmol) is suspended in MeOH (2 mL) and K2CO3 (0.015 g, 0.105 mmol) is added followed by tosylmethyl isocyanide (0.011 g, 0.058 mmol). The reaction mixture is heated to reflux under N2 for 16 hours. After cooling, additional tosylmethyl isocyanide (0.011 g, 0.058 mmol) is added and the reaction mixture heated to reflux under N2 for 16 hours. The reaction mixture is cooled to room temperature, concentrated under reduced pressure and dissolved in ethyl acetate. The organic solution is washed with water and brine. The combined aqueous washes are extracted with ethyl acetate. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure. Purification by flash column chromatography eluted with 20:1 methylene chloride:MeOH provides 4 mg (18%) desired product 10x and 1 mg (4%) (4-bromo-2-chloro-phenyl)-[4-fluoro-1-(2-methanesulfonyl-ethyl)-6-oxazol-5-yl-1H-benzoimidazol-5-yl]-amine.

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureto reflux under N2 for 16 hours
  3. temperatureAfter cooling
  4. temperaturethe reaction mixture heated
  5. temperatureto reflux under N2 for 16 hours
  6. concentrationconcentrated under reduced pressure
  7. dissolutiondissolved in ethyl acetate
  8. washThe organic solution is washed with water and brine
  9. extractionThe combined aqueous washes are extracted with ethyl acetate
  10. dry with materialThe combined organic extracts are dried (Na2SO4)
  11. concentrationconcentrated under reduced pressure
  12. customPurification by flash column chromatography
  13. washeluted with 20:1 methylene chloride

Sources & evidence

ORD record
ord-e88be9e2f8e1473c879f24fead77dabc
Source dataset
uspto-grants-2009_08
Patent number
US07576114B2

Reaction notes

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