Cesium fluoride → N-[6-(3,5-difluorophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

HRID 497611Notes

Reaction equation

HRID 497611 reaction equation
F[C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[F:8].[F-:12].[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>[F:12][C:3]1[CH:4]=[C:5]([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])([CH3:30])[CH3:29])=[CH:17][CH:16]=2)[CH:6]=[C:7]([F:8])[CH:2]=1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 27343373,4-Difluorobenzeneboronic acidHCID 10406687N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy)methyl]-1H-indazol-3-yl)butanamide

Product 1

HCID 10072215N-[6-(3,5-difluorophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamideYield 90.8%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

645 mg of 3,4-difluorophenylboronic 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 17 hours. The mixture is allowed to return to about 19° C. 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 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 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.). 1.1 g of N-[6-(3,5-difluorophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide are obtained in the form of an orange-coloured oil.

Workup

  1. customto return to about 19° C.
  2. filtrationfiltered through a sinter funnel
  3. customevaporated under reduced pressure (2 kPa; 50° C.)
  4. filtrationThe insoluble material is filtered off on a sinter funnel The organic phase
  5. dry with materialis dried over magnesium sulphate
  6. filtrationfiltered through a sinter funnel
  7. customevaporated under reduced pressure under the conditions
  8. customThe residue is purified by chromatography under an argon pressure of 50 kPa
  9. washon a column of silica gel (particle size 40-60 μm; diameter 3.5 cm), eluting with a cyclohexane/ethyl acetate mixture (80/20 by volume)
  10. customcollecting 35 cm3 fractions
  11. additionThe fractions containing the expected product
  12. customevaporated under reduced pressure (2 kPa; 50° C.)

Sources & evidence

ORD record
ord-3b7a2aa4207e49149d8c696e549fe4cc
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

Loading…