Styrene → N-[6-(2-phenylethyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

HRID 497617Notes

Reaction equation

HRID 497617 reaction equation
C12BC(CCC1)CCC2.[CH2:10]=[CH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[OH-].[Na+].Cl[C:21]1[CH:29]=[C:28]2[C:24]([C:25]([NH:38][C:39](=[O:43])[CH2:40][CH2:41][CH3:42])=[N:26][N:27]2[CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])=[CH:23][CH:22]=1.[F-].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.C(OCC)(=O)C.O>[C:12]1([CH2:11][CH2:10][C:21]2[CH:29]=[C:28]3[C:24]([C:25]([NH:38][C:39](=[O:43])[CH2:40][CH2:41][CH3:42])=[N:26][N:27]3[CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:35])[CH3:36])=[CH:23][CH:22]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

11

Reactant 5

HCID 7501StyreneHCID 14798Sodium HydroxideHCID 25953Cesium fluorideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 10406687N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy)methyl]-1H-indazol-3-yl)butanamide

Product 1

HCID 22319517N-[6-(2-phenylethyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

27.2 cm3 of 9-borabicyclo[3.3.1]nonane are added by syringe to a solution of 0.8 cm3 of styrene in 35 cm3 of dioxane and the mixture is heated at 75° C. for 1 hour. 5.5 cm3 of 5N sodium hydroxide are added to the cooled solution, followed by successive addition of 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide prepared in Example 25, 1.2 g of caesium fluoride, 32.2 mg of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl and 12.3 mg of palladium acetate, and the mixture is heated at reflux for 3 hours. After cooling, 50 cm3 of water and 75 cm3 of ethyl acetate are added; the organic phase is separated out after settling of the phases has taken place, dried over magnesium sulphate, filtered and concentrated under reduced pressure (2 kPa; 40° C.) to give 4.5 g of crude product, which is chromatographed 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 (75/25 by volume). The fractions containing the expected product are combined and then evaporated under reduced pressure (2 kPa; 40° C.) to give 1.4 g of N-[6-(2-phenylethyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

Workup

  1. temperaturethe mixture is heated
  2. temperatureat reflux for 3 hours
  3. temperatureAfter cooling
  4. customthe organic phase is separated out
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure (2 kPa; 40° C.)
  8. customto give 4.5 g of crude product, which
  9. customis chromatographed 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 (75/25 by volume)
  11. additionThe fractions containing the expected product
  12. customevaporated under reduced pressure (2 kPa; 40° C.)

Sources & evidence

ORD record
ord-40fd50ac95a04179adbdd2fddf6eb2a1
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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