Hydrochloric Acid → 5-amino-2-(4-amino-3-fluorophenyl)-6,8-difluoro-7-methyl-4H-1-benzopyran-4-one

HRID 1736152Notes

Reaction equation

HRID 1736152 reaction equation
Cl.[F:2][C:3]1[C:4]([CH3:36])=[C:5]([F:35])[C:6]2[O:11][C:10]([C:12]3[CH:17]=[CH:16][C:15]([NH:18]C(=O)C(C)(C)C)=[C:14]([F:25])[CH:13]=3)=[CH:9][C:8](=[O:26])[C:7]=2[C:27]=1[NH:28]C(=O)C(C)(C)C>O1CCOCC1>[NH2:28][C:27]1[C:7]2[C:8](=[O:26])[CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([NH2:18])=[C:14]([F:25])[CH:13]=3)[O:11][C:6]=2[C:5]([F:35])=[C:4]([CH3:36])[C:3]=1[F:2]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 106010646,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-7-methyl-5-pivaloylamino-4H-1-benzopyran-4-one

Product 1

HCID 3897105-amino-2-(4-amino-3-fluorophenyl)-6,8-difluoro-7-methyl-4H-1-benzopyran-4-oneYield 35%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

50 mL of 1,4-dioxane and 25 mL of concentrated hydrochloric acid were added to 800 mg (1.64 mmol) of the above 6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-7-methyl-5-pivaloylamino-4H-1-benzopyran-4-one and the mixture was stirred under heating at reflux for 2 hours. The reaction solution was poured into ice water, and the solution was made basic and extracted once with chloroform. The organic layer was washed once with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform:methanol=40:1) and recrystallized from ethyl acetate/n-hexane to give 183 mg of Compound 80 (yield: 35%).

Workup

  1. temperatureunder heating
  2. temperatureat reflux for 2 hours
  3. extractionextracted once with chloroform
  4. washThe organic layer was washed once with an aqueous saturated solution of sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (chloroform:methanol=40:1)
  8. customrecrystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-52f49ff8f28e481c942d7ecb16cf2eaa
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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