Ethyl Acetate → N-[6-(3,5-difluorophenyl)-1H-indazol-3-yl]butanamide

HRID 497612Notes

Reaction equation

HRID 497612 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[F:19][C:20]1[CH:21]=[C:22]([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]=[C:24]([F:26])[CH:25]=1.C(OCC)(=O)C>O1CCCC1>[F:19][C:20]1[CH:21]=[C:22]([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:23]=[C:24]([F:26])[CH:25]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium FluorideHCID 10072215N-[6-(3,5-difluorophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

Product 1

HCID 10041379N-[6-(3,5-difluorophenyl)-1H-indazol-3-yl]butanamideYield 43.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
66 °C

Procedure

14 cm3 of tetrabutylammonium fluoride as a 1M solution in tetrahydrofuran are added to 1.1 g of N-[6-(3,5-difluorophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously, in 30 cm3 of tetrahydrofuran. The reaction medium is heated at about 66° C. for 18 hours. The heating is then stopped and 100 cm3 of ethyl acetate are added. This mixture is washed with 2×50 cm3 of saturated aqueous sodium hydrogen carbonate solution and then with 50 cm3 of saturated aqueous sodium chloride solution. The organic phase is dried over magnesium sulphate, filtered through a sinter funnel and evaporated under reduced pressure (2 kPa; 50° 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 3.5 cm), eluting with cyclohexane/ethyl acetate (60/40 by volume) and collecting 35 cm3 fractions. The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). The residue is taken up in 2×5 cm3 of diisopropyl ether. This mixture is filtered through a sinter funnel and dried under reduced pressure (90 Pa; 50° C.) to give 340 mg of N-[6-(3,5-difluorophenyl)-1H-indazol-3-yl]butanamide in the form of a white solid melting at 260° C.

Workup

  1. washThis mixture is washed with 2×50 cm3 of saturated aqueous sodium hydrogen carbonate solution
  2. dry with materialThe organic phase is dried over magnesium sulphate
  3. filtrationfiltered through a sinter funnel
  4. customevaporated under reduced pressure (2 kPa; 50° C.)
  5. customThe residue is purified by chromatography under an argon pressure of 50 kPa
  6. washon a column of silica gel (particle size 40-60 μm; diameter 3.5 cm), eluting with cyclohexane/ethyl acetate (60/40 by volume)
  7. customcollecting 35 cm3 fractions
  8. additionThe fractions containing the expected product
  9. customevaporated under reduced pressure (2 kPa; 50° C.)
  10. filtrationThis mixture is filtered through a sinter funnel
  11. customdried under reduced pressure (90 Pa; 50° C.)

Sources & evidence

ORD record
ord-2e5f75a16db04297a846cb15969da1c0
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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