HCID 22319577, compound → HCID 135848026, compound

HRID 497705Notes

Reaction equation

HRID 497705 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][C:15]=2[C:16]2[CH:21]=[CH:20][C:19]([O:22]CC4C=CC=CC=4)=[CH:18][CH:17]=2)[NH:12][N:11]=[C:10]3[NH:30][C:31](=[O:35])[CH2:32][CH2:33][CH3:34])[CH:2]=1>C[Si](I)(C)C>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][C:15]=2[C:16]2[CH:17]=[CH:18][C:19]([OH:22])=[CH:20][CH:21]=2)[NH:12][N:11]=[C:10]3[NH:30][C:31](=[O:35])[CH2:32][CH2:33][CH3:34])[CH:2]=1

Participants

3

Reactant 1

HCID 22319577HCID 22319577, compound

Product 1

HCID 135848026HCID 135848026, compoundYield 24.3%

Reagents, catalysts & solvents 1

HCID 85247Trimethylsilyl iodideSolvent

Procedure

10 cm3 of trimethylsilyl iodide are added to 460 mg of N-[5-(3-pyridyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide, described previously, and the mixture is refluxed for 18 hours. The insoluble material is filtered off, washed with 2×20 cm3 of diethyl ether and taken up in 50 cm3 of tetrahydrofuran and 25 cm3 of ethyl acetate, and the organic phase is washed with 2×100 cm3 of 10% sodium thiosulphate solution, dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure to give 330 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 2.5 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.) and the residue is taken up in 10 cm3 of diisopropyl ether, filtered off, washed with 3×5 cm3 of diisopropyl ether, with 5 cm3 of ethyl acetate and then with 10 cm3 of diisopropyl ether and dried (90 Pa; 45° C.) to give 90 mg of N-[5-(3-pyridyl)-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide in the form of cream-coloured crystals melting at 165° C.

Workup

  1. temperaturethe mixture is refluxed for 18 hours
  2. filtrationThe insoluble material is filtered off
  3. washwashed with 2×20 cm3 of diethyl ether
  4. wash25 cm3 of ethyl acetate, and the organic phase is washed with 2×100 cm3 of 10% sodium thiosulphate solution
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure
  8. customto give 330 mg of crude product, which
  9. customis purified by chromatography under an argon pressure of 50 kPa
  10. washon a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with a cyclohexane/ethyl acetate mixture (50/50 by volume)
  11. additionThe fractions containing the expected product
  12. customevaporated under reduced pressure (2 kPa; 50° C.)
  13. filtrationfiltered off
  14. washwashed with 3×5 cm3 of diisopropyl ether, with 5 cm3 of ethyl acetate
  15. dry with materialwith 10 cm3 of diisopropyl ether and dried (90 Pa; 45° C.)

Sources & evidence

ORD record
ord-b3bc1119cc7844caa998536c7c09895b
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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