Sodium Hydroxide → 4-(4-Amino-2,3-difluorophenoxy)pyridine-2-carboxamide

HRID 2265721Notes

Reaction equation

HRID 2265721 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([F:9])[C:3]=1[F:10].NC1C(O)=C(F)C(F)=CC=1.CC(C)([O-])C.[K+].Cl[C:28]1[CH:33]=[CH:32][N:31]=[C:30]([C:34]([NH2:36])=[O:35])[CH:29]=1.[OH-].[Na+]>CS(C)=O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:28]2[CH:33]=[CH:32][N:31]=[C:30]([C:34]([NH2:36])=[O:35])[CH:29]=2)=[C:4]([F:9])[C:3]=1[F:10]

Participants

7

Reactant 5

HCID 14798Sodium HydroxideHCID 3035434-Chloropyridine-2-carboxamideHCID 27784416-Amino-2,3-difluorophenolHCID 27787664-Amino-2,3-difluorophenolHCID 23665647Potassium tert-butoxide

Product 1

HCID 574708784-(4-Amino-2,3-difluorophenoxy)pyridine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

The mixture of 4-amino-2,3-difluorophenol and 6-amino-2,3-difluorophenol (3.52 g) was dissolved in dimethyl sulfoxide (30 ml) under a nitrogen flow, and potassium tert-butoxide (1.49 g) was added at room temperature, followed by stirring for 30 min. 4-Chloropyridine-2-carboxamide (947 mg) was added thereto, followed by stirring at 80° C. for 6 hr. Then the reaction mixture was stirred at 100° C. for 14 hr. The reaction mixture was allowed to cool down to room temperature, and a 1N aqueous solution of sodium hydroxide (52.8 ml) was added, followed by stirring for 9 hr and 15 min. The reaction mixture was partitioned between ethyl acetate (300 ml) and water (300 ml). The aqueous layer was extracted with ethyl acetate (200 ml, twice), then the combined organic layer was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:3) and fractions containing the target compound were concentrated under reduced pressure. The residue was dried under reduced pressure to provide the titled compound as a pale brown solid (532 mg) which was a mixture of 4-(6-amino-2,3-difluorophenoxy)pyridine-2-carboxamide.

Workup

  1. additionwas added at room temperature
  2. stirringby stirring at 80° C. for 6 hr
  3. stirringThen the reaction mixture was stirred at 100° C. for 14 hr
  4. stirringby stirring for 9 hr and 15 min
  5. customThe reaction mixture was partitioned between ethyl acetate (300 ml) and water (300 ml)
  6. extractionThe aqueous layer was extracted with ethyl acetate (200 ml
  7. dry with materialtwice), then the combined organic layer was dried over anhydrous sodium sulfate
  8. customThe solvent was removed under reduced pressure
  9. customThe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:3) and fractions
  10. additioncontaining the target compound
  11. concentrationwere concentrated under reduced pressure
  12. customThe residue was dried under reduced pressure

Sources & evidence

ORD record
ord-a83309408c2b4b51ae279dfd315ec517
Source dataset
uspto-grants-2010_12
Patent number
US07855290B2

Reaction notes

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