Ethyl Acetate → N-(6-chloro-5-phenyl-1H-indazol-3-yl)butanamide

HRID 497649Notes

Reaction equation

HRID 497649 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[C:19]1([C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][C:33]=2[Cl:34])[N:30](COCC[Si](C)(C)C)[N:29]=[C:28]3[NH:43][C:44](=[O:48])[CH2:45][CH2:46][CH3:47])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(OCC)(=O)C>O1CCCC1>[C:19]1([C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][C:33]=2[Cl:34])[NH:30][N:29]=[C:28]3[NH:43][C:44](=[O:48])[CH2:45][CH2:46][CH3:47])[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium FluorideHCID 22319494N-[5-phenyl-6-chloro 1-[(2-trimethylsilylethoxy)methyl]indazol-3-yl]butanamide

Product 1

HCID 22319604N-(6-chloro-5-phenyl-1H-indazol-3-yl)butanamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
67 °C

Procedure

8.8 cm3 of tetrabutylammonium fluoride as a 1M solution in tetrahydrofuran are added to 650 mg of N-[5-phenyl-6-chloro-1-[[2-(trimethylsilyl]ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously, in 25 cm3 of tetrahydrofuran. The medium is maintained at 67° C. for 20 hours and is then allowed to return to room temperature and 75 cm3 of ethyl acetate are added; the organic phase is washed with 75 cm3 of saturated aqueous sodium hydrogen carbonate solution and then with 2×75 cm3 of saturated aqueous sodium chloride solution. The organic phase is dried over magnesium sulphate, filtered and evaporated to dryness 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 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 the residue is taken up in 15 cm3 of diisopropyl ether, filtered off on a sinter funnel and washed successively with 10 cm3 of diisopropyl ether and with 5 cm3 of ethyl acetate. After drying under reduced pressure (90 Pa; 50° C.), 240 mg of N-(5-phenyl-6-chloro-1H-indazol-3-yl)butanamide are obtained in the form of a white solid melting at 235° C.

Workup

  1. customto return to room temperature
  2. washthe organic phase is washed with 75 cm3 of saturated aqueous sodium hydrogen carbonate solution
  3. dry with materialThe organic phase is dried over magnesium sulphate
  4. filtrationfiltered
  5. customevaporated to dryness under reduced pressure (2 kPa; 45° C.)
  6. customThe residue is purified by chromatography under an argon pressure of 50 kPa
  7. 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)
  8. additionThe fractions containing the expected product
  9. customevaporated under reduced pressure (2 kPa; 50° C.)
  10. filtrationfiltered off on a sinter funnel
  11. washwashed successively with 10 cm3 of diisopropyl ether and with 5 cm3 of ethyl acetate
  12. dry with materialAfter drying under reduced pressure (90 Pa; 50° C.), 240 mg of N-(5-phenyl-6-chloro-1H-indazol-3-yl)butanamide

Sources & evidence

ORD record
ord-f1058de7707040d8b72b7bc81e4f730a
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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