Hydrochloric Acid → 5-amino-6-methyl-3-phenyl-1H-indazole

HRID 1452923Notes

Reaction equation

HRID 1452923 reaction equation
O.Cl.[CH3:3][C:4]1[CH:12]=[C:11]2[C:7]([C:8]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[N:9][NH:10]2)=[CH:6][C:5]=1[N+:19]([O-])=O.[OH-].[NH4+]>C(O)C.[Fe]>[NH2:19][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:4]=1[CH3:3])[NH:10][N:9]=[C:8]2[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14923Ammonium HydroxideHCID 22567058HCID 22567058, compound

Product 1

HCID 225673305-amino-6-methyl-3-phenyl-1H-indazoleYield 85.6%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Conditions

Temperature
20 °C

Procedure

5-Amino-6-methyl-3-phenyl-1H-indazole can be obtained in the following way: 0.5 ml of water and 0.18 ml of an aqueous 12N hydrochloric acid solution are added to a solution of 0.53 g of 6-methyl-5-nitro-3-phenyl-1H-indazole in 30 ml of ethanol. The reaction mixture is then heated at the reflux of the solvent and 0.36 g of powdered iron are added in 2 steps. The reaction mixture is then stirred at the reflux of the solvent for 4.5 hours and is then cooled to a temperature in the region of 20° C. and treated with 50 ml of ice-cold water. The mixture is then basified with an aqueous 32% ammonium hydroxide solution, to a pH in the region of 11. After settling out, the aqueous phase is extracted with one times 50 ml then 2 times 25 ml of ethyl acetate. The organic extracts are pooled, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue thus obtained is purified by chromatography on a silica column (particle size 63-200 μm), eluting with a cyclohexane/ethyl acetate (75/25 by volume) mixture. The fractions containing the expected product are pooled and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 0.4 g of 5-amino-6-methyl-3-phenyl-1H-indazole is thus obtained in the form of a beige crystalline solid melting at 133° C.

Workup

  1. temperatureThe reaction mixture is then heated at the
  2. additionare added in 2 steps
  3. temperaturereflux of the solvent for 4.5 hours
  4. extractionthe aqueous phase is extracted with one times 50 ml
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  8. customThe residue thus obtained
  9. customis purified by chromatography on a silica column (particle size 63-200 μm)
  10. washeluting with a cyclohexane/ethyl acetate (75/25 by volume) mixture
  11. additionThe fractions containing the expected product
  12. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-f122615bd52a46b09904fb5c68c089e8
Source dataset
uspto-grants-2009_01
Patent number
US07473701B2

Reaction notes

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