Acetic Anhydride → 4-Bromo-5-methoxy-1H-indazole

HRID 1802887Notes

Reaction equation

HRID 1802887 reaction equation
[Br:1][C:2]1[C:3]([CH3:11])=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][CH3:10])[NH2:5].C(OC(=O)C)(=O)C.C([O-])(=O)C.[K+].[N:24](OCCCCC)=O>C(#N)C>[Br:1][C:2]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[C:4]2[C:3]=1[CH:11]=[N:24][NH:5]2

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 10026Pentyl nitriteHCID 517044Potassium AcetateHCID 46941358HCID 46941358, compound

Product 1

HCID 469419134-Bromo-5-methoxy-1H-indazoleYield 52%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 3-bromo-4-methoxy-2-methylaniline (19.06 g) in acetonitrile (250 mL) was slowly added acetic anhydride (18.9 mL), and the mixture was stirred at room temperature for 1 hr. To the reaction mixture were added potassium acetate (2.60 g) and pentyl nitrite (22.3 g), and the mixture was heated under reflux for 8 hr. The reaction mixture was concentrated, and to the residue was added 6M hydrochloric acid (200 mL), and the mixture was heated under reflux overnight. The reaction mixture was neutralized with 8M sodium hydroxide, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4), and concentrated. The residue was dissolved in tetrahydrofuran, and the solution was treated with activated carbon. The activated carbon was filtered off, the filtrate was concentrated, and the obtained residue was crystallized from diisopropyl ether. The crystals were collected by filtration, washed with diisopropyl ether, and dried to give the title compound (10.42 g, yield 52%) as yellow crystals. melting point 178-180° C. MS: 229 (MH+).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 8 hr
  3. concentrationThe reaction mixture was concentrated
  4. additionto the residue was added 6M hydrochloric acid (200 mL)
  5. temperaturethe mixture was heated
  6. temperatureunder reflux overnight
  7. extractionthe mixture was extracted with ethyl acetate
  8. washThe ethyl acetate layer was washed with saturated brine
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated
  11. dissolutionThe residue was dissolved in tetrahydrofuran
  12. additionthe solution was treated with activated carbon
  13. filtrationThe activated carbon was filtered off
  14. concentrationthe filtrate was concentrated
  15. customthe obtained residue was crystallized from diisopropyl ether
  16. filtrationThe crystals were collected by filtration
  17. washwashed with diisopropyl ether
  18. customdried

Sources & evidence

ORD record
ord-626040816cc649f88cc5cff5476f9b59
Source dataset
uspto-grants-2013_01
Patent number
US08349886B2

Reaction notes

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