Sodium Carbonate → N-[6-[4-(dimethylamino)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

HRID 497673

Reaction equation

HRID 497673 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:5]([N:6]([CH3:8])[CH3:7])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].CC1(C)C(C)(C)OB([C:25]2[CH:33]=[C:32]3[C:28]([C:29]([NH:42][C:43](=[O:47])[CH2:44][CH2:45][CH3:46])=[N:30][N:31]3[CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])=[CH:27][CH:26]=2)O1>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.C(OCC)(=O)C>[CH3:7][N:6]([CH3:8])[C:5]1[CH:9]=[CH:10][C:2]([C:25]2[CH:33]=[C:32]3[C:28]([C:29]([NH:42][C:43](=[O:47])[CH2:44][CH2:45][CH3:46])=[N:30][N:31]3[CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:39])[CH3:40])=[CH:27][CH:26]=2)=[CH:3][CH:4]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 114654-bromo-N,N-dimethylanilineHCID 22319493N-[6-(4,4,5,5-tetramethyl [1,3,2]dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

Product 1

HCID 22319554N-[6-[4-(dimethylamino)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamideYield 17.3%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

785 mg of 4-bromo-N,N-dimethylaniline, 646 mg of sodium carbonate, 10 cm3 of water and 196 mg of tetrakis(triphenylphosphine)palladium are added to 1 g of N-[6-(4,4,5,5-tetramethyl [1,3,2]dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described in Example 56, in 50 cm3 of dioxane. The medium is then refluxed for 18 hours, the resulting mixture is then allowed to return to room temperature and 75 cm3 of ethyl acetate and 75 cm3 of water are added. The organic phase is dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45° C.) to give 1.6 g of crude product, which 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 (80/20 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). 170 mg of N-[6-[4-(dimethylamino)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide are obtained in the form of a yellow oil.

Workup

  1. temperatureThe medium is then refluxed for 18 hours
  2. customto return to room temperature
  3. dry with materialThe organic phase is dried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure (2 kPa; 45° C.)
  6. customto give 1.6 g of crude product, which
  7. customis 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 (80/20 by volume)
  9. additionThe fractions containing the expected product
  10. customevaporated under reduced pressure (2 kPa; 50° C.)

Sources & evidence

ORD record
ord-474b9ed8afb6473f8563ac084043e23c
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Linked notes

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