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

HRID 497605Notes

Reaction equation

HRID 497605 reaction equation
[O:1]1[CH:5]=[CH:4][C:3](B(O)O)=[CH:2]1.[F-].[Cs+].Cl[C:12]1[CH:20]=[C:19]2[C:15]([C:16]([NH:29][C:30](=[O:34])[CH2:31][CH2:32][CH3:33])=[N:17][N:18]2[CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])=[CH:14][CH:13]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:1]1[CH:5]=[CH:4][C:3]([C:12]2[CH:20]=[C:19]3[C:15]([C:16]([NH:29][C:30](=[O:34])[CH2:31][CH2:32][CH3:33])=[N:17][N:18]3[CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:26])[CH3:27])=[CH:14][CH:13]=2)=[CH:2]1

Participants

6

Reactant 3

HCID 25953Cesium fluoride2×HCID 2734358Furan-3-boronic acid2×HCID 10406687N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy)methyl]-1H-indazol-3-yl)butanamide

Product 1

HCID 10386231N-[6-(furan-3-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamideYield 12%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

457 mg of furan-3-boronic acid, 1.24 g of caesium fluoride, 13 mg of palladium acetate and finally 31 mg of 2-dicyclohexylphosphine-2-(N,N-dimethylamino)biphenyl are added to 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously in Example 25, in 30 cm3 of dioxane. The mixture is then heated at about 100° C. for 23 hours. A further 457 mg of furan-3-boronic acid, 1.24 g of caesium fluoride, 13 mg of palladium acetate and finally 31 mg of 2-dicyclohexylphosphine-2-(N,N-dimethylamino)biphenyl are added and refluxing is continued for 7 hours. The mixture is then allowed to return to about 19° C. over 16 hours and then filtered through a sinter funnel and evaporated under reduced pressure (2 kPa; 50° C.). The residue is rinsed with 50 cm3 of tetrahydrofuran and 50 cm3 of distilled water. The resulting residue is taken up in 75 cm3 of ethyl acetate and 50 cm3 of distilled water. 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 3.5 cm), eluting with a cyclohexane/ethyl acetate mixture (80/20 by volume) and collecting 35 cm3 fractions. The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). 130 mg of N-[6-(furan-3-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide are thus obtained in the form of an orange-coloured oil.

Workup

  1. temperaturerefluxing
  2. waitto return to about 19° C. over 16 hours
  3. filtrationfiltered through a sinter funnel
  4. customevaporated under reduced pressure (2 kPa; 50° C.)
  5. washThe residue is rinsed with 50 cm3 of tetrahydrofuran and 50 cm3 of distilled water
  6. dry with materialThe organic phase is dried over magnesium sulphate
  7. filtrationfiltered through a sinter funnel
  8. customevaporated under reduced pressure under the conditions
  9. customThe residue is purified by chromatography under an argon pressure of 50 kPa
  10. washon a column of silica gel (particle size 40-60 μm; diameter 3.5 cm), eluting with a cyclohexane/ethyl acetate mixture (80/20 by volume)
  11. customcollecting 35 cm3 fractions
  12. additionThe fractions containing the expected product
  13. customevaporated under reduced pressure (2 kPa; 50° C.)

Sources & evidence

ORD record
ord-e81eb3cd85ea48a7849b977fa440cbf6
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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