Ethyl Acetate → HCID 22319486, compound

HRID 497630Notes

Reaction equation

HRID 497630 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[CH3:19][C:20]([C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:37]=[C:36]3[C:32]([C:33]([NH:46][C:47](=[O:51])[CH2:48][CH2:49][CH3:50])=[N:34][N:35]3COCC[Si](C)(C)C)=[CH:31][CH:30]=2)=[CH:25][CH:24]=1)([CH3:22])[CH3:21].C(OCC)(=O)C>O1CCCC1>[CH3:22][C:20]([C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:37]=[C:36]3[C:32]([C:33]([NH:46][C:47](=[O:51])[CH2:48][CH2:49][CH3:50])=[N:34][NH:35]3)=[CH:31][CH:30]=2)=[CH:25][CH:24]=1)([CH3:19])[CH3:21]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium FluorideHCID 22319497HCID 22319497, compound

Product 1

HCID 22319486HCID 22319486, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
66 °C

Procedure

14.6 cm3 of tetrabutylammonium fluoride as a 1M solution in tetrahydrofuran are added to 1.13 g of N-[6-[4-(1,1-dimethylethyl)phenyl]-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 22 hours, the heating is then stopped and 75 cm3 of ethyl acetate are added, and the organic phase is washed with 75 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 and concentrated to dryness 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 2.5 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.); the residue is taken up in 10 cm3 of diisopropyl ether, filtered off on a sinter funnel and washed successively with 10 cm3 of diisopropyl ether and then with 2×5 cm3 of ethyl acetate. After drying (90 Pa; 50° C.), 320 mg of N-[6-[4-(1,1-dimethylethyl)phenyl]-1H-indazol-3-yl]butanamide are thus obtained in the form of a white product melting at 246° C.

Workup

  1. washthe organic phase is washed with 75 cm3 of saturated aqueous sodium hydrogen carbonate solution
  2. dry with materialThe organic phase is dried over magnesium sulphate
  3. filtrationfiltered
  4. concentrationconcentrated to dryness 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 2.5 cm), eluting with a cyclohexane/ethyl acetate mixture (70/30 by volume)
  7. additionThe fractions containing the expected product
  8. customevaporated under reduced pressure (2 kPa; 50° C.)
  9. filtrationfiltered off on a sinter funnel
  10. washwashed successively with 10 cm3 of diisopropyl ether
  11. dry with materialAfter drying (90 Pa; 50° C.), 320 mg of N-[6-[4-(1,1-dimethylethyl)phenyl]-1H-indazol-3-yl]butanamide

Sources & evidence

ORD record
ord-75bcaa121b584469a03927e6a5345edf
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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