Trimethylsilyl iodide → N-(6-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl)butyramide

HRID 497666Notes

Reaction equation

HRID 497666 reaction equation
C[Si](I)(C)C.[Cl:6][C:7]1[CH:12]=[C:11]([O:13]CC2C=CC=CC=2)[CH:10]=[CH:9][C:8]=1[C:21]1[CH:29]=[C:28]2[C:24]([C:25]([NH:30][C:31](=[O:35])[CH2:32][CH2:33][CH3:34])=[N:26][NH:27]2)=[CH:23][CH:22]=1>CO>[Cl:6][C:7]1[CH:12]=[C:11]([OH:13])[CH:10]=[CH:9][C:8]=1[C:21]1[CH:29]=[C:28]2[C:24]([C:25]([NH:30][C:31](=[O:35])[CH2:32][CH2:33][CH3:34])=[N:26][NH:27]2)=[CH:23][CH:22]=1

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 22319505N-[6-[2-chloro-4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide

Product 1

HCID 135433925N-(6-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl)butyramideYield 50.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

15 cm3 of trimethylsilyl iodide are added to 0.6 g of N-[6-[2-chloro-4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide, described previously, and the mixture is refluxed for 4 hours, followed by addition of 50 cm3 of methanol, and refluxing is continued for 15 minutes. The reaction medium is concentrated to dryness under reduced pressure (2 kPa; 50° C.), 100 cm3 of ethyl acetate are added and the organic phase is washed with 2×50 cm3 of 10% sodium thiosulphate solution and then with 50 cm3 of saturated sodium chloride solution. The organic phase is separated out after settling of the phases has taken place, dried over magnesium sulphate, filtered and concentrated to dryness. The crude product obtained 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 (60/40 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.); 0.24 g of N-[6-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]butanamide is obtained in the form of a white foam.

Workup

  1. temperaturethe mixture is refluxed for 4 hours
  2. temperaturerefluxing
  3. concentrationThe reaction medium is concentrated to dryness under reduced pressure (2 kPa; 50° C.), 100 cm3 of ethyl acetate
  4. additionare added
  5. washthe organic phase is washed with 2×50 cm3 of 10% sodium thiosulphate solution
  6. customThe organic phase is separated out
  7. dry with materialdried over magnesium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe crude product obtained
  11. customis purified by chromatography under an argon pressure of 50 kPa
  12. washon a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with a cyclohexane/ethyl acetate mixture (60/40 by volume)
  13. additionThe fractions containing the expected product
  14. customevaporated under reduced pressure (2 kPa; 50° C.)

Sources & evidence

ORD record
ord-00c551311aeb451c903d33309557b040
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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