Ethanol → 6-Bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine

HRID 244678Notes

Reaction equation

HRID 244678 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([N+:17]([O-])=O)[C:5]2[C:9]([CH:10]=1)=[N:8][N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[CH:6]=2.[Cl-].[NH4+].C(O)C>[Fe].O.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([NH2:17])[C:5]2[C:9]([CH:10]=1)=[N:8][N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[CH:6]=2

Participants

7

Reactant 3

HCID 702EthanolHCID 25517Ammonium ChlorideHCID 582558186-Bromo-4-nitro-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole

Product 1

HCID 582557836-Bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amineYield 72.5%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

6-Bromo-4-nitro-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole (6 g, 18.40 mmol), iron filings (3.29 g, 58.9 mmol) and ammonium chloride (0.492 g, 9.20 mmol) were weighed to a 250 ml flask and ethanol (60 ml) then water (18 ml) was added. The reaction was heated to 80° C. for 2.5 hr. The reaction mixture was cooled. 100 ml ethyl acetate and 50 ml water was added. There was no visible separation of layers so the reaction was evaporated to remove the ethyl acetate and ethanol. 250 ml ethyl acetate was then added and the organic layer was washed with a further 50 ml water, before passing through a hydrophobic frit. The organic layer was evaporated to dryness and purified by column chromatography on silica (120 g silica column, ISCO companion technology) eluting with a gradient of 1-2% methanol in DCM over 25 minutes. Fractions containing desired material were combined and evaporated to dryness to afford the title compound (3.95 g).

Workup

  1. temperatureThe reaction mixture was cooled
  2. customno visible separation of layers so the reaction
  3. customwas evaporated
  4. customto remove the ethyl acetate and ethanol
  5. addition250 ml ethyl acetate was then added
  6. washthe organic layer was washed with a further 50 ml water
  7. customThe organic layer was evaporated to dryness
  8. custompurified by column chromatography on silica (120 g silica column, ISCO companion technology)
  9. washeluting with a gradient of 1-2% methanol in DCM over 25 minutes
  10. additionFractions containing desired material
  11. customevaporated to dryness

Sources & evidence

ORD record
ord-dd0833cdd7fe414fbe5c682af8301b65
Source dataset
uspto-grants-2014_02
Patent number
US08658635B2

Reaction notes

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