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

HRID 520575Notes

Reaction equation

HRID 520575 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-amine

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), iron filings (3.29 g) and ammonium chloride (0.492 g) were weighed to a 250 ml round-bottomed flask and ethanol (60 ml) then water (18 ml) were added. The reaction was heated to 80° C. for 2.5 h. The reaction mixture was cooled. Ethyl acetate (100 ml) and water (50 ml) were added. There was no visible separation of layers so the reaction was concentrated to remove the ethyl acetate and ethanol. Ethyl acetate (250 ml) was then added and the organic layer was washed with water (50 ml), before passing through a hydrophobic frit. The organic layer was evaporated to dryness. The residue was purified by column chromatography on silica (120 g silica column, ISCO Companion) eluting with a gradient of 1-2% methanol in DCM over 25 min. 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. concentrationwas concentrated
  4. customto remove the ethyl acetate and ethanol
  5. additionEthyl acetate (250 ml) was then added
  6. washthe organic layer was washed with water (50 ml)
  7. customThe organic layer was evaporated to dryness
  8. customThe residue was purified by column chromatography on silica (120 g silica column, ISCO Companion)
  9. washeluting with a gradient of 1-2% methanol in DCM over 25 min
  10. additionFractions containing desired material
  11. customevaporated to dryness

Sources & evidence

ORD record
ord-fa37666dc0aa46b6a7d9572f221d95a4
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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