Potassium Carbonate → 4-fluoro-6-oxazol-5-yl-1H-benzoimidazol-5-yl-amine

HRID 1176914Notes

Reaction equation

HRID 1176914 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>[F:24][C:23]1[C:13]2[N:14]=[CH:15][NH:16][C:12]=2[CH:11]=[C:10]([C:25]2[O:26][CH:46]=[N:45][CH:44]=2)[C:9]=1[NH2:8].[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 21114189(4-bromo-2-chloro-phenyl)-[4-fluoro-1-(2-methanesulfonyl-ethyl)-6-oxazol-5-yl-1H-benzoimidazol-5-yl]-amineYield 4%HCID 866171194-fluoro-6-oxazol-5-yl-1H-benzoimidazol-5-yl-amineYield 18%

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 following 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 gives 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. additionis added
  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-a27460ea8a744659b2d1d8c8fd6542b7
Source dataset
uspto-grants-2010_11
Patent number
US07842816B2

Reaction notes

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