Trimethylsilyl iodide → HCID 135546072, compound

HRID 497651Notes

Reaction equation

HRID 497651 reaction equation
C[Si](I)(C)C.[Br:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][C:15]=1[C:16]1[CH:21]=[CH:20][C:19]([O:22]CC3C=CC=CC=3)=[CH:18][CH:17]=1)[NH:12][N:11]=[C:10]2[NH:30][C:31](=[O:35])[CH2:32][CH2:33][CH3:34]>CO>[Br:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][C:15]=1[C:16]1[CH:17]=[CH:18][C:19]([OH:22])=[CH:20][CH:21]=1)[NH:12][N:11]=[C:10]2[NH:30][C:31](=[O:35])[CH2:32][CH2:33][CH3:34]

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 22319576HCID 22319576, compound

Product 1

HCID 135546072HCID 135546072, compoundYield 32.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

10 cm3 of trimethylsilyl iodide are added to 500 mg of N-[5-bromo-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide, prepared previously, and the mixture is refluxed for 4 hours. 25 cm3 of methanol are added and the reaction medium is refluxed for 15 minutes and then concentrated to dryness under reduced pressure (2 kPa; 50° C.). The residue is taken up in 50 cm3 of ethyl acetate and is washed with 2×50 cm3 of 10% sodium thiosulphate solution and then with 50 cm3 of water and 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 then concentrated to dryness under reduced pressure to give 1 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 3.5 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.) and the residue is taken up in 10 cm3 of ethyl acetate, filtered off, washed with 2×5 cm3 of ethyl acetate and dried (90 Pa; 45° C.) to give 130 mg of N-[5-bromo-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide melting above 260° C.

Workup

  1. customprepared previously
  2. temperaturethe mixture is refluxed for 4 hours
  3. temperaturethe reaction medium is refluxed for 15 minutes
  4. concentrationconcentrated to dryness under reduced pressure (2 kPa; 50° C.)
  5. washis 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 under reduced pressure
  10. customto give 1 g of crude product, which
  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 3.5 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.)
  15. filtrationfiltered off
  16. washwashed with 2×5 cm3 of ethyl acetate
  17. customdried (90 Pa; 45° C.)

Sources & evidence

ORD record
ord-6e563f32fcbd445e9701fc7c507324ce
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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