Ethyl Acetate → HCID 22319577, compound

HRID 497704Notes

Reaction equation

HRID 497704 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[N:19]1[CH:24]=[CH:23][CH:22]=[C:21]([C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][C:33]=2[C:34]2[CH:39]=[CH:38][C:37]([O:40][CH2:41][C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=4)=[CH:36][CH:35]=2)[N:30](COCC[Si](C)(C)C)[N:29]=[C:28]3[NH:56][C:57](=[O:61])[CH2:58][CH2:59][CH3:60])[CH:20]=1.C(OCC)(=O)C>O1CCCC1>[N:19]1[CH:24]=[CH:23][CH:22]=[C:21]([C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][C:33]=2[C:34]2[CH:35]=[CH:36][C:37]([O:40][CH2:41][C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=4)=[CH:38][CH:39]=2)[NH:30][N:29]=[C:28]3[NH:56][C:57](=[O:61])[CH2:58][CH2:59][CH3:60])[CH:20]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium FluorideHCID 22319531HCID 22319531, compound

Product 1

HCID 22319577HCID 22319577, compoundYield 84.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

7.1 cm3 of tetrabutylammonium fluoride as a 1M solution in tetrahydrofuran are added to 700 mg of N-[5-(3-pyridyl)-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously, in 50 cm3 of tetrahydrofuran, and the mixture is refluxed for 18 hours; after cooling, 75 cm3 of ethyl acetate are added and the organic phase is washed successively with 2×75 cm3 of saturated sodium hydrogen carbonate solution and then with 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 concentrated to dryness under reduced pressure (2 kPa; 50° C.) to give 850 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 (70/30 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.); the residue is dried (90 Pa; 45° C.) to give 460 mg of N-[5-(3-pyridyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide in the form of cream-coloured crystals.

Workup

  1. temperaturethe mixture is refluxed for 18 hours
  2. temperatureafter cooling
  3. washthe organic phase is washed successively with 2×75 cm3 of saturated sodium hydrogen carbonate solution
  4. customThe organic phase is separated out
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure (2 kPa; 50° C.)
  8. customto give 850 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 3 cm), eluting with a cyclohexane/ethyl acetate mixture (70/30 by volume)
  11. additionThe fractions containing the expected product
  12. customevaporated under reduced pressure (2 kPa; 50° C.)
  13. customthe residue is dried (90 Pa; 45° C.)

Sources & evidence

ORD record
ord-d78cb8a2479e42798ef931efd158db43
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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