Ethyl Acetate → HCID 22319657, compound

HRID 497710Notes

Reaction equation

HRID 497710 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Br:19][C:20]1[CH:21]=[C:22]2[C:26](=[C:27]([F:30])[C:28]=1[F:29])[N:25](COCC[Si](C)(C)C)[N:24]=[C:23]2[NH:39][C:40](=[O:44])[CH2:41][CH2:42][CH3:43].C(OCC)(=O)C.C(=O)([O-])O.[Na+]>O1CCCC1>[Br:19][C:20]1[CH:21]=[C:22]2[C:26](=[C:27]([F:30])[C:28]=1[F:29])[NH:25][N:24]=[C:23]2[NH:39][C:40](=[O:44])[CH2:41][CH2:42][CH3:43]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 2724141Tetrabutylammonium FluorideHCID 10095181HCID 10095181, compound

Product 1

HCID 22319657HCID 22319657, compoundYield 40.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

9.4 cm3 of tetrabutylammonium fluoride as a 1M solution in tetrahydrofuran are added to 700 mg of N-[5-bromo-6,7-difluoro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously, in 30 cm3 of tetrahydrofuran, and the mixture is refluxed for 18 hours; after cooling, 100 cm3 of ethyl acetate and 75 cm3 of saturated sodium hydrogen carbonate solution are added and the organic phase is then washed successively with 75 cm3 of saturated sodium hydrogen carbonate solution and with 75 cm3 of saturated sodium chloride solution. The organic phase is separated out after settling of the phases has taken place, dried over magnesium sulphate and concentrated to dryness under reduced pressure (2 kPa; 50° C.) to give 850 mg of crude product, which 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 cyclohexane/ethyl acetate mixture (80/20 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 8 cm3 of diisopropyl ether, filtered off, washed with 3 cm3 of diisopropyl ether, dried under reduced pressure (90 Pa; 45° C.) to give 200 mg of N-(5-bromo-6,7-difluoro-1H-indazol-3-yl)butanamide in the form of white crystals melting at 220° C.

Workup

  1. temperaturethe mixture is refluxed for 18 hours
  2. temperatureafter cooling
  3. washthe organic phase is then washed successively with 75 cm3 of saturated sodium hydrogen carbonate solution and with 75 cm3 of saturated sodium chloride solution
  4. customThe organic phase is separated out
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated to dryness under reduced pressure (2 kPa; 50° C.)
  7. customto give 850 mg of crude product, which
  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 cyclohexane/ethyl acetate mixture (80/20 by volume)
  10. additionThe fractions containing the expected product
  11. customevaporated under reduced pressure (2 kPa; 50° C.)
  12. filtrationfiltered off
  13. washwashed with 3 cm3 of diisopropyl ether
  14. customdried under reduced pressure (90 Pa; 45° C.)

Sources & evidence

ORD record
ord-2855454a5bd44932904f6a92bdb5da07
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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