Hydrochloric Acid → 6-Nitro-1H-indazole-3-carboxylic acid

HRID 747100Notes

Reaction equation

HRID 747100 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][C:7]([N+:11]([O-:13])=[O:12])=[CH:8][CH:9]=2)[NH:4][N:3]=1.[Cu]C#N.C(C1C2C(=CC([N+]([O-])=O)=CC=2)NN=1)#N.[N+](C1C=C2C(C=NN2)=CC=1)([O-])=[O:32].Cl.CN(C)[CH:46]=[O:47]>[OH-].[Na+]>[N+:11]([C:7]1[CH:6]=[C:5]2[C:10]([C:2]([C:46]([OH:47])=[O:32])=[N:3][NH:4]2)=[CH:9][CH:8]=1)([O-:13])=[O:12]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 242396-Nitroindazole2×HCID 669325916-Nitro-1h-indazole-3-carbonitrile2×HCID 178418546HCID 178418546, compoundHCID 178526460HCID 178526460, compound

Product 1

HCID 231188596-Nitro-1H-indazole-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Conditions

Temperature
100 °C

Procedure

A 5 mL microwave reaction vessel was charged with 3-iodo-6-nitroindazole (1 mmol), copper (I) cyanide (2 mmol) and N,N-dimethylformamide (3 mL). The vessel was sealed and subjected to microwave irradiation at 185° C. for 600 sec. The reaction mixture was partitioned between ethyl acetate (100 mL) and water (100 ML) and the mixture was filtered through Celite. The organic layer was collected, washed with brine, dried (magnesium sulfate), and concentrated to give 122 mg of a 10/1 mixture of 3-cyano-6-nitroindazole and 6-nitroindazole as a yellow solid. The 10/1 mixture of 3-cyano-6-nitroindazole and 6-nitroindazole was dissolved in 10 N sodium hydroxide and the bright orange solution was heated at 100° C. for 1 h. The mixture was allowed to cool to room temperature and carefully acidified (pH=1) with 3N hydrochloric acid. The solid was isolated and triturated with EtOAc to provide 51 mg of 6-nitroindazole-3-carboxylic acid as a brown solid. The acid was coupled with the bicyclobase according to procedure A.

Workup

  1. customThe vessel was sealed
  2. customirradiation at 185° C. for 600 sec
  3. customThe reaction mixture was partitioned between ethyl acetate (100 mL) and water (100 ML)
  4. filtrationthe mixture was filtered through Celite
  5. customThe organic layer was collected
  6. washwashed with brine
  7. dry with materialdried (magnesium sulfate)
  8. concentrationconcentrated
  9. customto give
  10. temperatureto cool to room temperature
  11. customThe solid was isolated
  12. customtriturated with EtOAc

Sources & evidence

ORD record
ord-5456223722e24d9f9a455a71a771b37e
Source dataset
uspto-grants-2008_07
Patent number
US07396833B2

Reaction notes

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