Pyridine → HCID 10095181, compound

HRID 497709Notes

Reaction equation

HRID 497709 reaction equation
N1C=CC=CC=1.[F:7][C:8]1[C:16]([F:17])=[C:15]2[C:11]([C:12]([NH:26][C:27](=[O:31])[CH2:28][CH2:29][CH3:30])=[N:13][N:14]2[CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])=[CH:10][CH:9]=1.[Br:32]Br.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)(Cl)Cl.ClCCl>[Br:32][C:9]1[CH:10]=[C:11]2[C:15](=[C:16]([F:17])[C:8]=1[F:7])[N:14]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:23])[CH3:24])[N:13]=[C:12]2[NH:26][C:27](=[O:31])[CH2:28][CH2:29][CH3:30]

Participants

7

Reactant 4

HCID 1049PyridineHCID 24408BromineHCID 24477Sodium ThiosulfateHCID 10248536HCID 10248536, compound

Product 1

HCID 10095181HCID 10095181, compound

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

0.87 cm3 of pyridine is added to 1 g of N-[6,7-difluoro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously, in 30 cm3 of chloroform, followed by addition of 0.56 cm3 of bromine, and the mixture is refluxed overnight. 50 cm3 of dichloromethane and 50 cm3 of aqueous 10% sodium thiosulphate solution are added to the reaction medium. After stirring for 10 minutes, the insoluble material is removed by filtration on a sinter funnel and the organic phase is washed with 50 cm 3 of water and with 50 cm3 of saturated 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; 45° C.). The crude product, 1.1 g, 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 cyclohexane/ethyl acetate mixture (90/10 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). After drying (90 Pa; 45° C.), 230 mg of N-(5-bromo-6,7-difluoro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl)butanamide are obtained in the form of a colourless oil.

Workup

  1. temperaturethe mixture is refluxed overnight
  2. customthe insoluble material is removed by filtration on a sinter funnel
  3. washthe organic phase is washed with 50 cm 3 of water and with 50 cm3 of saturated sodium chloride solution
  4. customThe organic phase is separated out
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure (2 kPa; 45° C.)
  8. customThe crude product, 1.1 g, is purified by chromatography under an argon pressure of 50 kPa
  9. washon a column of silica gel (particle size 40-60 μm; diameter 3 cm), eluting with a cyclohexane/ethyl acetate mixture (90/10 by volume)
  10. additionThe fractions containing the expected product
  11. customevaporated under reduced pressure (2 kPa; 50° C.)
  12. dry with materialAfter drying (90 Pa; 45° C.), 230 mg of N-(5-bromo-6,7-difluoro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl)butanamide
  13. customare obtained in the form of a colourless oil

Sources & evidence

ORD record
ord-525370f08bb840d29d763d16a2d2e97f
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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