Hydrazine hydrate (1:1) → 3-amino-1H-indazole-5-carboxylic Acid

HRID 880940Notes

Reaction equation

HRID 880940 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1F)[C:6]([OH:8])=[O:7])#[N:2].O.[NH2:14][NH2:15]>C(O)C>[NH2:2][C:1]1[C:3]2[C:11](=[CH:10][CH:9]=[C:5]([C:6]([OH:8])=[O:7])[CH:4]=2)[NH:15][N:14]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 27739323-Cyano-4-fluorobenzoic acid

Product 1

HCID 115718843-amino-1H-indazole-5-carboxylic AcidYield 58.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 3-cyano-4-fluorobenzoic acid (980.0 mg, 5.94 mmol) in ethanol (6 mL), was added hydrazine hydrate (0.89 mL, 17.8 mmol). The reaction was heated at reflux for 3 hours. The reaction was cooled to room temperature and ethanol was removed under reduced pressure. The resultant yellow oil was taken up in water (50 mL) and basified with 1 N aqueous sodium hydroxide (5 mL). The solution was washed once with ethyl acetate (25 mL). The aqueous phase was acidified to pH=3 with 6 N aqueous hydrochloric acid and was allowed to stir at room temperature for 1 hour. The resulting precipitate was collected by filtration and dried under vacuum to give the title compound (612 mg, 48%) as a pink solid. +ESI (M+H) 178.1; 1H NMR (400 MHz, DMSO-d6, δ): 8.42-8.47 (m, 1H), 7.76 (dd, J=8.8, 1.6 Hz, 1H), 7.21 (d, J=8.8 Hz, 1H).

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 3 hours
  3. customethanol was removed under reduced pressure
  4. washThe solution was washed once with ethyl acetate (25 mL)
  5. filtrationThe resulting precipitate was collected by filtration
  6. customdried under vacuum

Sources & evidence

ORD record
ord-f990c746bf204c84b8f8f16c7a70545a
Source dataset
uspto-grants-2015_03
Patent number
US08993586B2

Reaction notes

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