Ethyl Acetate → 4-fluoro-1H-indazole-5-carbonitrile

HRID 1983522Notes

Reaction equation

HRID 1983522 reaction equation
[F:1][C:2]1[C:9]([CH:10]=O)=[C:8](F)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].O.[NH2:14][NH2:15].C(OCC)(=O)C>O1CCCC1.CO>[F:1][C:2]1[C:3]([C:4]#[N:5])=[CH:6][CH:7]=[C:8]2[C:9]=1[CH:10]=[N:14][NH:15]2

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 24654Hydrazine hydrate (1:1)HCID 106071732,4-Difluoro-3-formylbenzonitrile

Product 1

HCID 222606314-fluoro-1H-indazole-5-carbonitrile

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A total of 8.55 g of 2,4-difluoro-3-formyl-benzonitrile obtained in Production Example II-13-a was dissolved in 40 ml of tetrahydrofuran and 40 ml of methanol, and 5.1 ml of hydrazine monohydrate was added, followed by stirring at room temperature for three days and was further stirred at 50° C. for 3 hours and at 70° C. for 3 hours. The reaction mixture was added with 150 ml of ice-water, 300 ml of ethyl acetate and 100 ml of tetrahydrofuran were added, and unnecessary matters were filtered off. The organic layer was sequentially washed with water and brine, dried over anhydrous magnesium sulfate and the solvent was evaporated. The crude product was purified and separated by silica gel column chromatography (ethyl acetate:toluene=1:9 to 1:4), to give 509 mg of the title compound as bright yellow crystals. In addition, a portion with impurities was purified again by silica gel column chromatography (ethyl acetate:n-hexane=1:4 to 1:0), to give 1.80 g of the title compound as bright yellow crystals.

Workup

  1. stirringwas further stirred at 50° C. for 3 hours and at 70° C. for 3 hours
  2. additionwere added
  3. filtrationunnecessary matters were filtered off
  4. washThe organic layer was sequentially washed with water and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated
  7. customThe crude product was purified
  8. customseparated by silica gel column chromatography (ethyl acetate:toluene=1:9 to 1:4)

Sources & evidence

ORD record
ord-5597e8310ae74f558637461eafa1b0af
Source dataset
uspto-grants-2009_06
Patent number
US07541376B2

Reaction notes

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