Ethanol → 5-Fluoro-4-methoxy-1H-indazol-3-amine

HRID 1874693Notes

Reaction equation

HRID 1874693 reaction equation
[F:1][C:2]1[C:3](OC)=[C:4]([C:7](F)=[CH:8][CH:9]=1)[C:5]#[N:6].[OH2:13].[NH2:14][NH2:15].[CH2:16](O)C>>[F:1][C:2]1[C:3]([O:13][CH3:16])=[C:4]2[C:7](=[CH:8][CH:9]=1)[NH:15][N:14]=[C:5]2[NH2:6]

Participants

4

Reactant 3

HCID 702EthanolHCID 24654Hydrazine hydrate (1:1)HCID 457907333,6-Difluoro-2-methoxybenzonitrile

Product 1

HCID 580545685-Fluoro-4-methoxy-1H-indazol-3-amineYield 25%

Procedure

A mixture of 3,6-difluoro-2-methyloxybenzonitrile (for a preparation see Intermediate 55) (30 g, 184 mmol) in ethanol (300 mL) was reacted with Hydrazine Monohydrate (Alfa, 89 mL, 1.84 mol, 10 equiv.). The resulting mixture was heated at reflux overnight then allowed to cool to room temperature. Silica was added to the mixture which was then evaporated to dryness. The pre-absorbed crude reaction mixture was then purified by chromatography eluting with petrol up to EtOAc (10% steps, 500 mL per step) to give the title compound (8.4 g, 25%) as a yellow solid.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux overnight
  3. additionSilica was added to the mixture which
  4. customwas then evaporated to dryness
  5. customThe pre-absorbed crude
  6. customreaction mixture
  7. customwas then purified by chromatography
  8. washeluting with petrol up to EtOAc (10% steps, 500 mL per step)

Sources & evidence

ORD record
ord-1fd327dcbf4f48dd91e4cf82a0ea9d64
Source dataset
uspto-grants-2012_11
Patent number
US08304446B2

Reaction notes

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