Ethyl Acetate → HCID 22319567, compound

HRID 497694Notes

Reaction equation

HRID 497694 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](B(O)O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][C:33]=1[Cl:34])[N:30]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[N:29]=[C:28]2[NH:43][C:44](=[O:48])[CH2:45][CH2:46][CH3:47].C(OCC)(=O)C>O.O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:34][C:33]1[CH:32]=[C:31]2[C:27]([C:28]([NH:43][C:44](=[O:48])[CH2:45][CH2:46][CH3:47])=[N:29][N:30]2[CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:40])[CH3:41])=[CH:26][C:25]=1[C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:10][CH:11]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 27343144-Benzyloxy-phenylboronic acidHCID 22319528N-[5-bromo-6-chloro-1-[(2-trimethylsilylethoxy)methyl]indazol-3-yl]butanamide

Product 1

HCID 22319567HCID 22319567, compoundYield 95.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

1.54 g of 4-benzyloxyphenylboronic acid, 1.32 g of sodium carbonate in 20 cm3 of water and 404 mg of tetrakis(triphenylphosphine)palladium are added to 2 g of N-[5-bromo-6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described in Example 58, in 100 cm3 of dioxane. The mixture is refluxed for 18 hours, the temperature is then allowed to return to room temperature to add 75 cm3 of ethyl acetate and 50 cm3 of water, and the reaction medium is filtered through a sinter funnel packed with Celite. The filtrate is separated by settling and the organic phase is washed successively with 100 cm3 of water and then with 75 cm3 of saturated aqueous sodium chloride solution, separated out after settling of the phases has taken place, 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 4.5 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 50 cm3 of cyclohexane, filtered off, washed with 2×25 cm3 of cyclohexane and dried under reduced pressure (90 Pa; 50° C.) to give 2.35 g of N-[6-chloro-5-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of white crystals melting at 130° C.

Workup

  1. temperatureThe mixture is refluxed for 18 hours
  2. customto return to room temperature
  3. filtrationthe reaction medium is filtered through a sinter funnel
  4. customThe filtrate is separated
  5. washthe organic phase is washed successively with 100 cm3 of water
  6. customwith 75 cm3 of saturated aqueous sodium chloride solution, separated out
  7. dry with materialdried over magnesium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness under reduced pressure (2 kPa; 50° C.)
  10. customThe residue is purified by chromatography under an argon pressure of 50 kPa
  11. washon a column of silica gel (particle size 40-60/μm; diameter 4.5 cm), eluting with a cyclohexane/ethyl acetate mixture (80/20 by volume)
  12. additionThe fractions containing the expected product
  13. customevaporated under reduced pressure (2 kPa; 50° C.)
  14. filtrationfiltered off
  15. washwashed with 2×25 cm3 of cyclohexane
  16. customdried under reduced pressure (90 Pa; 50° C.)

Sources & evidence

ORD record
ord-68dd6dda06074bb3bd934b34e94e8f79
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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