Tetrabutylammonium Fluoride → N-[6-(4-cyanophenyl)-1H-indazol-3-yl]butanamide

HRID 497712Notes

Reaction equation

HRID 497712 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[C:19]([C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:35]=[C:34]3[C:30]([C:31]([NH:44][C:45](=[O:49])[CH2:46][CH2:47][CH3:48])=[N:32][N:33]3COCC[Si](C)(C)C)=[CH:29][CH:28]=2)=[CH:23][CH:22]=1)#[N:20]>O1CCCC1.C(OCC)(=O)C>[C:19]([C:21]1[CH:22]=[CH:23][C:24]([C:27]2[CH:35]=[C:34]3[C:30]([C:31]([NH:44][C:45](=[O:49])[CH2:46][CH2:47][CH3:48])=[N:32][NH:33]3)=[CH:29][CH:28]=2)=[CH:25][CH:26]=1)#[N:20]

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 22319570HCID 22319570, compound

Product 1

HCID 22319584N-[6-(4-cyanophenyl)-1H-indazol-3-yl]butanamideYield 42.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

3.0 cm3 of tetrabutylammonium fluoride as a 1M solution in tetrahydrofuran are added to 400 mg of N-[6-(4-cyanophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously, in 10 cm3 of tetrahydrofuran, and the mixture is refluxed for 18 hours. The reaction medium is diluted with 20 cm3 of ethyl acetate and the organic phase is washed successively with 20 cm3 of saturated sodium hydrogen carbonate solution, with 2×20 cm3 of water 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 then concentrated 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 cm), eluting with a methylene chloride/methanol gradient (100/0 to 98/2 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.); 120 mg of N-[6-(4-cyanophenyl)-1H-indazol-3-yl]butanamide are obtained in the form of a solid melting at 242° C.

Workup

  1. temperaturethe mixture is refluxed for 18 hours
  2. washthe organic phase is washed successively with 20 cm3 of saturated sodium hydrogen carbonate solution, with 2×20 cm3 of water and with 20 cm3 of saturated sodium chloride solution
  3. customThe organic phase is separated out
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure (2 kPa; 50° C.)
  7. customThe crude product obtained
  8. customis purified by chromatography under an argon pressure of 50 kPa
  9. washon a column of silica gel (particle size 40-60 μm; diameter 3 cm), eluting with a methylene chloride/methanol gradient (100/0 to 98/2 by volume)
  10. additionThe fractions containing the expected product
  11. customevaporated under reduced pressure (2 kPa; 50° C.)

Sources & evidence

ORD record
ord-bb8a034099544d21aa81f4cae603f921
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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