Tetrahydrofuran → N-[6-(4-Hydroxyphenyl)-1h-Indazol-3-Yl]butanamide

HRID 497609Notes

Reaction equation

HRID 497609 reaction equation
I[Si](C)(C)C.O1CCCC1.C1(C[O:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:33]=[C:32]4[C:28]([C:29]([NH:34][C:35](=[O:39])[CH2:36][CH2:37][CH3:38])=[N:30][NH:31]4)=[CH:27][CH:26]=3)=[CH:21][CH:20]=2)C=CC=CC=1>C(#N)C>[OH:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]2[CH:33]=[C:32]3[C:28]([C:29]([NH:34][C:35](=[O:39])[CH2:36][CH2:37][CH3:38])=[N:30][NH:31]3)=[CH:27][CH:26]=2)=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 85247Trimethylsilyl iodide2×HCID 10452673N-(6-(4-(benzyloxy)phenyl)-1H-indazol-3-yl)butyramide

Product 1

HCID 135458003N-[6-(4-Hydroxyphenyl)-1h-Indazol-3-Yl]butanamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
82 °C

Procedure

0.15 cm3 of iodotrimethylsilane and then 5 cm3 of tetrahydrofuran are added to 200 mg of N-[6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide, described previously, in 7.5 cm3 of acetonitrile, and the medium is heated at about 82° C. for 2 hours. 0.15 cm3 of iodotrimethylsilane is added and heating is continued for 17 hours. The reaction medium is then evaporated to dryness under reduced pressure (2 kPa; 40° C.). The residue is taken up in 75 cm3 of ethyl acetate, and this mixture is then washed with 2×50 cm3 of saturated aqueous sodium sulphate solution and with 50 cm3 of saturated sodium chloride solution. The organic phase is dried over magnesium sulphate, filtered and then evaporated under reduced pressure (2 kPa; 45° C.). The residue is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 1.5 cm), eluting with ethyl acetate and collecting 30 cm3 fractions. The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). The residue is washed with 3×5 cm3 of diisopropyl ether. It is filtered off on a sinter funnel and, after drying (90 Pa; 40° C.), 100 mg of N-[6-(4-hydroxyphenyl)]-1H-indazol-3-yl]butanamide are thus obtained in the form of a white solid melting at about 235° C.

Workup

  1. temperatureheating
  2. customThe reaction medium is then evaporated to dryness under reduced pressure (2 kPa; 40° C.)
  3. washthis mixture is then washed with 2×50 cm3 of saturated aqueous sodium sulphate solution and with 50 cm3 of saturated sodium chloride solution
  4. dry with materialThe organic phase is dried over magnesium sulphate
  5. filtrationfiltered
  6. customevaporated under reduced pressure (2 kPa; 45° C.)
  7. customThe residue is purified by chromatography under an argon pressure of 50 kPa
  8. washon a column of silica gel (particle size 40-60 μm; diameter 1.5 cm), eluting with ethyl acetate
  9. customcollecting 30 cm3 fractions
  10. additionThe fractions containing the expected product
  11. customevaporated under reduced pressure (2 kPa; 50° C.)
  12. washThe residue is washed with 3×5 cm3 of diisopropyl ether
  13. filtrationIt is filtered off on a sinter funnel
  14. dry with materialafter drying (90 Pa; 40° C.), 100 mg of N-[6-(4-hydroxyphenyl)]-1H-indazol-3-yl]butanamide

Sources & evidence

ORD record
ord-e0a7a4bab6bb4fb484349749fb3776a4
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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