Ethyl Acetate → HCID 22319530, compound

HRID 497671Notes

Reaction equation

HRID 497671 reaction equation
[F-:1].[CH2:2]([N+](CCCC)(CCCC)CCCC)[CH2:3][CH2:4]C.[Cl:19][C:20]1[CH:28]=[C:27]2[C:23]([C:24]([NH:37][C:38](=[O:42])[CH2:39][CH2:40][CH3:41])=[N:25][N:26]2[CH2:29]OCC[Si](C)(C)C)=[CH:22][C:21]=1C1C=CC(F)=CC=1.C(O[CH2:54][CH3:55])(=O)C>O1CCCC1>[Cl:19][C:20]1[CH:28]=[C:27]2[C:23]([C:24]([NH:37][C:38](=[O:42])[CH2:39][CH2:40][CH3:41])=[N:25][N:26]2[C:29]2[CH:55]=[CH:54][C:4]([F:1])=[CH:3][CH:2]=2)=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium FluorideHCID 22319506HCID 22319506, compound

Product 1

HCID 22319530HCID 22319530, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

9.5 cm of tetrabutylammonium fluoride as a 1M solution in tetrahydrofuran are added to 0.73 g of N-[6-chloro-5-(4-fluorophenyl)-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide, described previously, in 20 cm3 of tetrahydrofuran, and the mixture is refluxed for 18 hours; after cooling, 30 cm3 of ethyl acetate are added and the organic phase is washed successively with 2×20 cm3 of saturated sodium hydrogen carbonate solution and with 20 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.); the crude product obtained 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.) and dried (90 Pa; 45° C.) to give 200 mg of N-[6-chloro-(4-fluorophenyl)-1H-indazol-3-yl]butanamide in the form of a cream-coloured powder.

Workup

  1. temperaturethe mixture is refluxed for 18 hours
  2. temperatureafter cooling
  3. washthe organic phase is washed successively with 2×20 cm3 of saturated sodium hydrogen carbonate solution and with 20 cm3 of saturated sodium chloride 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. customthe crude product obtained
  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 3.5 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. customdried (90 Pa; 45° C.)

Sources & evidence

ORD record
ord-0f3144a62a95472e915c87657d3c073a
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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