Potassium Carbonate → 4-[(6-Chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-3-fluoroaniline

HRID 16417Notes

Reaction equation

HRID 16417 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([F:9])[CH:3]=1.CC(C)([O-])C.[K+].C(=O)([O-])[O-].[K+].[K+].[Cl:22][C:23]1[N:28]=[C:27]2[NH:29][CH:30]=[CH:31][C:26]2=[C:25]([N+]([O-])=O)[CH:24]=1>CN(C=O)C.C(OCC)(=O)C>[Cl:22][C:23]1[N:28]=[C:27]2[NH:29][CH:30]=[CH:31][C:26]2=[C:25]([O:8][C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][C:4]=2[F:9])[CH:24]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 2735918Phenol, 4-amino-2-fluoro-HCID 179793386-chloro-4-nitro-1H-pyrrolo[2,3-b]pyridineHCID 23665647Potassium tert-butoxide

Product 1

HCID 179792844-[(6-Chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-3-fluoroaniline

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Amino-2-fluorophenol (0.77 g, 6.07 mmol) is dissolved in DMF. Potassium tert-butoxide (0.68 g, 6.07 mmol) is added, and the mixture is stirred at room temperature for 30 minutes. Powdered potassium carbonate (0.35 g, 2.53 mmol) and 1 g (5.06 mmol) of 6-chloro-4-nitro-1H-pyrrolo[2,3-b]pyridine (from example XXX) are then added successively. The mixture is stirred at 120° C. for 12 hours. After cooling, the mixture is diluted with ethyl acetate (200 ml). The suspension is filtered off with suction through Celite®, and the filtercake is washed with ethyl acetate. The solution is extracted successively with aqueous sodium bicarbonate solution and sodium chloride solution. The organic phase is dried over anhydrous magnesium sulfate and concentrated. The residue is purified by column chromatography (silica gel 60, mobile phase: DCM:acetone=5:1). This gives 0.95 g (67% of theory) of product.

Workup

  1. stirringThe mixture is stirred at 120° C. for 12 hours
  2. temperatureAfter cooling
  3. filtrationThe suspension is filtered off with suction through Celite®
  4. washthe filtercake is washed with ethyl acetate
  5. extractionThe solution is extracted successively with aqueous sodium bicarbonate solution and sodium chloride solution
  6. dry with materialThe organic phase is dried over anhydrous magnesium sulfate
  7. concentrationconcentrated
  8. customThe residue is purified by column chromatography (silica gel 60, mobile phase: DCM:acetone=5:1)

Sources & evidence

ORD record
ord-ea0e983032304f259c08a3a0dfb9a679
Source dataset
uspto-grants-2010_06
Patent number
US07737153B2

Reaction notes

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