Trimethylsilyl iodide → HCID 22319607, compound

HRID 497696Notes

Reaction equation

HRID 497696 reaction equation
C[Si](I)(C)C.[Cl:6][C:7]1[CH:15]=[C:14]2[C:10]([C:11]([NH:16][C:17](=[O:21])[CH2:18][CH2:19][CH3:20])=[N:12][NH:13]2)=[CH:9][C:8]=1[C:22]1[CH:27]=[CH:26][C:25]([O:28]CC2C=CC=CC=2)=[CH:24][CH:23]=1>CO>[Cl:6][C:7]1[CH:15]=[C:14]2[C:10]([C:11]([NH:16][C:17](=[O:21])[CH2:18][CH2:19][CH3:20])=[N:12][NH:13]2)=[CH:9][C:8]=1[C:22]1[CH:23]=[CH:24][C:25]([OH:28])=[CH:26][CH:27]=1

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 22319550HCID 22319550, compound

Product 1

HCID 22319607HCID 22319607, compoundYield 24.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

20 cm3 of trimethylsilyl iodide are added to 1.1 g of N-[6-chloro-5-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide, prepared in Example 95, and the mixture is refluxed for 18 hours. 30 cm3 of methanol are added and the reaction medium is refluxed for 30 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 100 cm3 of water and the organic phase is washed with 2×75 cm3 of 10% sodium thiosulphate solution and then with 70 cm3 of water and 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 1.44 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 (70/30 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 20 cm3 of diisopropyl ether, filtered off, washed with 3×10 cm3 of diisopropyl ether and then dried (90 Pa; 45° C.) to give 210 mg of N-[6-chloro-5-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide in the form of a white powder.

Workup

  1. customprepared in Example 95
  2. temperaturethe mixture is refluxed for 18 hours
  3. temperaturethe reaction medium is refluxed for 30 minutes
  4. concentrationconcentrated to dryness under reduced pressure (2 kPa; 50° C.)
  5. wash100 cm3 of water and the organic phase is washed with 2×75 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 1.44 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 (70/30 by volume)
  13. additionThe fractions containing the expected product
  14. customevaporated under reduced pressure (2 kPa; 50° C.)
  15. filtrationfiltered off
  16. washwashed with 3×10 cm3 of diisopropyl ether
  17. customdried (90 Pa; 45° C.)

Sources & evidence

ORD record
ord-789fd30f6d064233995faf31c3472c5e
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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