Tetrahydrofuran → 3-Amino-6,7-difluoro-1H-indazole

HRID 497618Notes

Reaction equation

HRID 497618 reaction equation
O.[NH2:2][NH2:3].F[C:5]1[C:12]([F:13])=[C:11]([F:14])[CH:10]=[CH:9][C:6]=1[C:7]#[N:8].C(OCC)(=O)C.O1CCCC1>C(O)C.O>[F:14][C:11]1[C:12]([F:13])=[C:5]2[C:6]([C:7]([NH2:8])=[N:2][NH:3]2)=[CH:9][CH:10]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 8857Ethyl AcetateHCID 24654Hydrazine hydrate (1:1)HCID 5189362,3,4-Trifluorobenzonitrile

Product 1

HCID 103972023-Amino-6,7-difluoro-1H-indazole

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

0.32 cm3 of hydrazine monohydrate is added to 0.46 cm3 of 2,3,4-trifluorobenzonitrile in 10 cm3 of absolute ethanol. The medium is heated at about 75° C. for 17 hours and then 10 cm3 of ethyl acetate, 5 cm3 of tetrahydrofuran and 5 cm3 of distilled water are added. The organic phase is separated out after settling of the phases has taken place, and is washed again with 10 cm3 of distilled water and then with 10 cm3 of saturated aqueous sodium chloride solution. The organic phase is separated out after settling of the phases has taken place, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50° C.). The residue obtained is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 1.5 cm), eluting with a cyclohexane/ethyl acetate mixture (50/50 by volume). The fractions containing the expected product are combined and then evaporated under reduced pressure (2 kPa; 40° C.); after drying (90 Pa; 40° C.), 100 mg of 6,7-difluoro-1H-indazole-3-amine are obtained in the form of a white solid melting at 183° C.

Workup

  1. customThe organic phase is separated out
  2. washis washed again with 10 cm3 of distilled water
  3. customThe organic phase is separated out
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure (2 kPa; 50° C.)
  7. customThe residue obtained
  8. customis purified by chromatography under an argon pressure of 50 kPa
  9. washon a column of silica gel (particle size 40-60 μm; diameter 1.5 cm), eluting with a cyclohexane/ethyl acetate mixture (50/50 by volume)
  10. additionThe fractions containing the expected product
  11. customevaporated under reduced pressure (2 kPa; 40° C.)
  12. dry with materialafter drying (90 Pa; 40° C.), 100 mg of 6,7-difluoro-1H-indazole-3-amine

Sources & evidence

ORD record
ord-28c285f93fb14a998e6e8a99c6dbd3d1
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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