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

HRID 497641Notes

Reaction equation

HRID 497641 reaction equation
I[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].CC1(C)C(C)(C)OB([C:22]2[CH:30]=[C:29]3[C:25]([C:26]([NH:39][C:40](=[O:44])[CH2:41][CH2:42][CH3:43])=[N:27][N:28]3[CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])=[CH:24][CH:23]=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>[N:5]1[CH:6]=[CH:7][C:2]([C:22]2[CH:30]=[C:29]3[C:25]([C:26]([NH:39][C:40](=[O:44])[CH2:41][CH2:42][CH3:43])=[N:27][N:28]3[CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:36])[CH3:37])=[CH:24][CH:23]=2)=[CH:3][CH:4]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 6094924-IodopyridineHCID 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 22319546N-[6-(4-pyridyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamideYield 97.9%

Reagents, catalysts & solvents 4

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

Procedure

246 mg of 4-iodopyridine, 10 cm3 of water, 201 mg of sodium carbonate and 69 mg of tetrakis(triphenylphosphine)palladium are added to 320 mg 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 previously, in 20 cm3 of dioxane. The medium is refluxed for 20 hours, the mixture is then allowed to return to room temperature and 50 cm3 of ethyl acetate and 50 cm3 of water are added. The combined organic phases are washed with 50 cm3 of distilled water and then with 50 cm3 of saturated aqueous sodium chloride solution, and then dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45° C.). 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 2.5 cm), eluting with a cyclohexane/ethyl acetate mixture (70/30 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). 280 mg of N-[6-(4-pyridyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide are obtained in the form of a yellow oil.

Workup

  1. temperatureThe medium is refluxed for 20 hours
  2. customto return to room temperature
  3. washThe combined organic phases are washed with 50 cm3 of distilled water
  4. dry with materialwith 50 cm3 of saturated aqueous sodium chloride solution, and then dried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure (2 kPa; 45° C.)
  7. customThe residue is 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 (70/30 by volume)
  9. additionThe fractions containing the expected product
  10. customevaporated under reduced pressure (2 kPa; 50° C.)

Sources & evidence

ORD record
ord-1b96e967136149fc83214999daacc8a2
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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