Cesium fluoride → (6-(2-propenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

HRID 497625Notes

Reaction equation

HRID 497625 reaction equation
[F-].[Cs+].[CH2:3](B1OC(C)(C)C(C)(C)O1)[CH:4]=[CH2:5].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=[CH:32][CH:31]=[CH:30][C:29]=2[N:34](C)C)CCCCC1.Cl[C:44]1[CH:52]=[C:51]2[C:47]([C:48](NC(=O)CCC)=[N:49][N:50]2[CH2:53][O:54][CH2:55][CH2:56][Si:57]([CH3:60])([CH3:59])[CH3:58])=[CH:46][CH:45]=1.[O:67]1CCOCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:5]([C:44]1[CH:52]=[C:51]2[C:47]([C:48]([CH:30]([CH2:31][CH3:32])[C:29]([NH2:34])=[O:67])=[N:49][N:50]2[CH2:53][O:54][CH2:55][CH2:56][Si:57]([CH3:58])([CH3:59])[CH3:60])=[CH:46][CH:45]=1)[CH:4]=[CH2:3]

Participants

7

Reactant 5

HCID 25953Cesium fluorideHCID 312751,4-DioxaneHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 27631714,4,5,5-Tetramethyl-2-(prop-2-en-1-yl)-1,3,2-dioxaborolaneHCID 10406687N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy)methyl]-1H-indazol-3-yl)butanamide

Product 1

HCID 86759853(6-(2-propenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

1.24 g of caesium fluoride, 0.77 cm3 of 2-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, 31.5 mg of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)-biphenyl and 13.5 mg of palladium acetate are successively added to a solution of 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl)butanamide, prepared in Example 25, in 30 cm3 of dioxane, and the mixture is refluxed for 18 hours. The reaction medium is filtered and taken up in 2×50 cm3 of ethyl acetate, and the organic phase is washed successively with 50 cm3 of water and 50 cm3 of saturated sodium chloride solution. After separating out the organic phase by settling, drying over sodium sulphate, filtration and concentration to dryness under reduced pressure (2 kPa; 50° C.) 1.3 g of brown oil are obtained, which is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 4.5 cm), eluting with a cyclohexane/ethyl acetate mixture (90/10 by volume). After concentration and drying (90 Pa; 45° C.), 0.72 g of N-[(6-(2-propenyl-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide is obtained in the form of a yellow oil in a purity of 75%.

Workup

  1. temperaturethe mixture is refluxed for 18 hours
  2. filtrationThe reaction medium is filtered
  3. washthe organic phase is washed successively with 50 cm3 of water and 50 cm3 of saturated sodium chloride solution
  4. customAfter separating out the organic phase
  5. dry with materialdrying over sodium sulphate, filtration and concentration to dryness under reduced pressure (2 kPa; 50° C.) 1.3 g of brown oil
  6. customare obtained
  7. customwhich is purified by chromatography under an argon pressure of 50 kPa
  8. washon a column of silica gel (particle size 40-60 μm; diameter 4.5 cm), eluting with a cyclohexane/ethyl acetate mixture (90/10 by volume)
  9. concentrationAfter concentration
  10. dry with materialdrying (90 Pa; 45° C.), 0.72 g of N-[(6-(2-propenyl-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide
  11. customis obtained in the form of a yellow oil in a purity of 75%

Sources & evidence

ORD record
ord-ba1620444342462492cdcb4703678032
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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