Pyridine → HCID 10095181, compound

HRID 1744844Notes

Reaction equation

HRID 1744844 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 above 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 thiosulfate 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 cm3 of water and with 50 cm3 of saturated sodium chloride solution. The organic phase is separated out by settling of the phases, dried over magnesium sulfate, 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 colorless 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 cm3 of water and with 50 cm3 of saturated sodium chloride solution
  4. customThe organic phase is separated out
  5. dry with materialdried over magnesium sulfate
  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 colorless oil

Sources & evidence

ORD record
ord-42469025ffe8456b8a48ed4f0ed1dfae
Source dataset
uspto-grants-2006_03
Patent number
US07019011B2

Reaction notes

Loading…