Butyryl chloride → N-(6,7-difluoro-1H-indazol-3-yl)butanamide

HRID 2217360Notes

Reaction equation

HRID 2217360 reaction equation
[C:1](Cl)(=[O:5])[CH2:2][CH2:3][CH3:4].[F:7][C:8]1[C:16]([F:17])=[C:15]2[C:11]([C:12]([NH2:18])=[N:13][NH:14]2)=[CH:10][CH:9]=1>N1C=CC=CC=1>[F:7][C:8]1[C:16]([F:17])=[C:15]2[C:11]([C:12]([NH:18][C:1](=[O:5])[CH2:2][CH2:3][CH3:4])=[N:13][NH:14]2)=[CH:10][CH:9]=1

Participants

4

Reactant 2

HCID 8855Butyryl chlorideHCID 103972023-Amino-6,7-difluoro-1H-indazole

Product 1

HCID 11776377N-(6,7-difluoro-1H-indazol-3-yl)butanamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
3 °C

Procedure

0.61 cm3 of butyryl chloride is added to 1 g of 6,7-difluoro-1H-indazole-3-amine described above, in 15 cm3 of pyridine, after having cooled to about 3° C., and the mixture is then left at ambient temperature for 76 hours. The reaction medium is concentrated under reduced pressure (2 kPa; 40° C.) and the residue is taken up in 25 cm3 of ethyl acetate and 25 cm3 of water. The organic phase is washed with 25 cm3 of distilled water and then with 25 cm3 of saturated aqueous sodium chloride solution. After drying over magnesium sulfate, filtering and concentrating under reduced pressure (2 kPa; 40° 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 3 cm), eluting with a dichloromethane/methanol mixture (98/2 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.), 596 mg of N-(6,7-difluoro-1H-indazol-3-yl)butanamide are obtained in the form of a white solid melting at 191° C.

Workup

  1. concentrationThe reaction medium is concentrated under reduced pressure (2 kPa; 40° C.)
  2. washThe organic phase is washed with 25 cm3 of distilled water
  3. dry with materialAfter drying over magnesium sulfate
  4. filtrationfiltering
  5. concentrationconcentrating under reduced pressure (2 kPa; 40° C.)
  6. customthe residue obtained
  7. customis purified by chromatography under an argon pressure of 50 kPa
  8. washon a column of silica gel (particle size 40-60 μm; diameter 3 cm), eluting with a dichloromethane/methanol mixture (98/2 by volume)
  9. additionThe fractions containing the expected product
  10. customevaporated under reduced pressure (2 kPa; 40° C.)
  11. dry with materialafter drying (90 Pa ; 40° C.), 596 mg of N-(6,7-difluoro-1H-indazol-3-yl)butanamide

Sources & evidence

ORD record
ord-19610c9f755c498d89ca7dcc9bee8444
Source dataset
uspto-grants-2008_08
Patent number
US07407981B2

Reaction notes

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