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

HRID 497613Notes

Reaction equation

HRID 497613 reaction equation
[S: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>[S: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 fluorideHCID 581760Thiophene-3-boronic acidHCID 10406687N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy)methyl]-1H-indazol-3-yl)butanamide

Product 1

HCID 10364554N-[6-(3-thiophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamideYield 50.5%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

522 mg of 3-thienylboronic 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 2 hours. 31 mg of 2-dicyclohexylphosphine-2-(N,N-dimethylamino)biphenyl and 13 mg of palladium acetate are added and the mixture is refluxed for 17 hours. The mixture is then allowed to return to about 19° C. and then filtered through a sinter funnel, and 75 cm3 of ethyl acetate and 50 cm3 of distilled water are added. The insoluble material is filtered off on a sinter funnel. 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 4.5 cm), eluting with a cyclohexane/ethyl acetate mixture (90/10 by volume) and collecting 50 cm3 fractions. The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). 570 mg of N-[6-(3-thiophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide are obtained in the form of a yellow oil.

Workup

  1. temperaturethe mixture is refluxed for 17 hours
  2. customto return to about 19° C.
  3. filtrationfiltered through a sinter funnel
  4. addition75 cm3 of ethyl acetate and 50 cm3 of distilled water are added
  5. filtrationThe insoluble material is filtered off on a sinter funnel
  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 4.5 cm), eluting with a cyclohexane/ethyl acetate mixture (90/10 by volume)
  11. customcollecting 50 cm3 fractions
  12. additionThe fractions containing the expected product
  13. customevaporated under reduced pressure (2 kPa; 50° C.)

Sources & evidence

ORD record
ord-9955206809d04aed89bcaa044e739e4c
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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