Trimethylsilyl iodide → HCID 135848031, compound

HRID 497702Notes

Reaction equation

HRID 497702 reaction equation
C[Si](I)(C)C.[CH2:6]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:15]=[C:16]3[C:20](=[CH:21][C:22]=2[C:23]2[CH:28]=[CH:27][C:26]([O:29]CC4C=CC=CC=4)=[CH:25][CH:24]=2)[NH:19][N:18]=[C:17]3[NH:37][C:38](=[O:42])[CH2:39][CH2:40][CH3:41])=[CH:10][CH:9]=1)[CH3:7]>CO>[CH2:6]([C:8]1[CH:9]=[CH:10][C:11]([C:14]2[CH:15]=[C:16]3[C:20](=[CH:21][C:22]=2[C:23]2[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=2)[NH:19][N:18]=[C:17]3[NH:37][C:38](=[O:42])[CH2:39][CH2:40][CH3:41])=[CH:12][CH:13]=1)[CH3:7]

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 22319490HCID 22319490, compound

Product 1

HCID 135848031HCID 135848031, compoundYield 36.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

10 cm3 of trimethylsilyl iodide are added to 600 mg of N-[5-(4-ethylphenyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide, described previously, and the mixture is refluxed for 18 hours. 30 cm3 of methanol are added and the reaction medium is refluxed for 5 minutes and then concentrated to dryness under reduced pressure (2 kPa; 50° C.). The residue is taken up in 100 cm3 of ethyl acetate and the organic phase is washed with 2×100 cm3 of 10% sodium thiosulphate solution and then with 75 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 650 mg 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 cm), eluting with a cyclohexane/ethyl acetate mixture (50/50 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.); the residue is taken up in 15 cm3 of diisopropyl ether, filtered off, washed with 5 cm3 of ethyl acetate and then with 10 cm3 of diisopropyl ether, and dried (90 Pa; 45° C.) to give 180 mg of N-[5-(4-ethylphenyl)-6-(4-hydroxyphenyl)-1H-indazol-3-yl]-butanamide in the form of cream-coloured crystals melting at 225° C.

Workup

  1. temperaturethe mixture is refluxed for 18 hours
  2. temperaturethe reaction medium is refluxed for 5 minutes
  3. concentrationconcentrated to dryness under reduced pressure (2 kPa; 50° C.)
  4. washthe organic phase is washed with 2×100 cm3 of 10% sodium thiosulphate solution
  5. customThe organic phase is separated out
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure
  9. customto give 650 mg of crude product, which
  10. customis purified by chromatography under an argon pressure of 50 kPa
  11. washon a column of silica gel (particle size 40-60 μm; diameter 3 cm), eluting with a cyclohexane/ethyl acetate mixture (50/50 by volume)
  12. additionThe fractions containing the expected product
  13. customevaporated under reduced pressure (2 kPa; 50° C.)
  14. filtrationfiltered off
  15. washwashed with 5 cm3 of ethyl acetate
  16. dry with materialwith 10 cm3 of diisopropyl ether, and dried (90 Pa; 45° C.)

Sources & evidence

ORD record
ord-467ac52f2fc74c428a69c590126fc59c
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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