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

HRID 497600Notes

Reaction equation

HRID 497600 reaction equation
C(B(CC)[C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1)C.[F-].[Cs+].Cl[C:15]1[CH:23]=[C:22]2[C:18]([C:19]([NH:32][C:33](=[O:37])[CH2:34][CH2:35][CH3:36])=[N:20][N:21]2[CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])=[CH:17][CH:16]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:6]1[CH:7]=[CH:8][CH:9]=[C:4]([C:15]2[CH:23]=[C:22]3[C:18]([C:19]([NH:32][C:33](=[O:37])[CH2:34][CH2:35][CH3:36])=[N:20][N:21]3[CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:29])[CH3:30])=[CH:17][CH:16]=2)[CH:5]=1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 6428513-(Diethylboryl)pyridineHCID 10406687N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy)methyl]-1H-indazol-3-yl)butanamide

Product 1

HCID 10386888N-[6-(3-pyridyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

900 mg of diethyl-3-pyridylborane, 1.86 g of caesium fluoride, 18.4 mg of palladium acetate and finally 48 mg of 2-dicyclohexylphosphine-2-(N,N-dimethylamino)biphenyl are added to 1.5 g of N-[6-chloro-1-[[2(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously, in 40 cm3 of dioxane. The mixture is then heated at about 100° C. for 17 hours and then filtered through a sinter funnel and evaporated under reduced pressure (2 kPa; 50° C.). The residue is taken up in 75 cm3 of ethyl acetate and 50 cm3 of distilled water. The organic phase is washed again with 50 cm3 of distilled water and with 50 cm3 of saturated aqueous sodium chloride solution. The organic phase is dried over magnesium sulphate, filtered through a sinter funnel and then evaporated under reduced pressure under the conditions described previously. The residue is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with a cyclohexane/ethyl acetate mixture (50/50 by volume) and collecting 25 cm3 fractions. The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). After drying (90 Pa; 50° C.), 900 mg of N-[6-(3-pyridyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide are thus obtained in the form of a yellow oil.

Workup

  1. filtrationfiltered through a sinter funnel
  2. customevaporated under reduced pressure (2 kPa; 50° C.)
  3. washThe organic phase is washed again with 50 cm3 of distilled water and with 50 cm3 of saturated aqueous sodium chloride solution
  4. dry with materialThe organic phase is dried over magnesium sulphate
  5. filtrationfiltered through a sinter funnel
  6. customevaporated under reduced pressure under the conditions
  7. customThe residue is purified by chromatography under an argon pressure of 50 kPa
  8. washon a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with a cyclohexane/ethyl acetate mixture (50/50 by volume)
  9. customcollecting 25 cm3 fractions
  10. additionThe fractions containing the expected product
  11. customevaporated under reduced pressure (2 kPa; 50° C.)
  12. dry with materialAfter drying (90 Pa; 50° C.), 900 mg of N-[6-(3-pyridyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide
  13. customare thus obtained in the form of a yellow oil

Sources & evidence

ORD record
ord-5fdba49861bb444a899ecd5b9126d7fb
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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