Ethyl Acetate → HCID 22319531, compound

HRID 497703Notes

Reaction equation

HRID 497703 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(CC)CC)[CH:2]=1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][C:27]=1[C:28]1[CH:33]=[CH:32][C:31]([O:34][CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[CH:30][CH:29]=1)[N:24]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[N:23]=[C:22]2[NH:50][C:51](=[O:55])[CH2:52][CH2:53][CH3:54].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>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:19]2[CH:20]=[C:21]3[C:25](=[CH:26][C:27]=2[C:28]2[CH:29]=[CH:30][C:31]([O:34][CH2:35][C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)=[CH:32][CH:33]=2)[N:24]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:47])([CH3:48])[CH3:49])[N:23]=[C:22]3[NH:50][C:51](=[O:55])[CH2:52][CH2:53][CH3:54])[CH:2]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 6428513-(Diethylboryl)pyridineHCID 22319485HCID 22319485, compound

Product 1

HCID 22319531HCID 22319531, compoundYield 160.5%

Reagents, catalysts & solvents 3

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

Procedure

371 mg of 3-pyridyldiethylborane, 428 mg of sodium carbonate in 30 cm3 of water, and 258 mg of tetrakis(triphenylphosphine)palladium are added to 1 g of N-[5-bromo-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, prepared in Example 63, in 100 cm3 of dioxane, and the mixture is refluxed for 18 hours. 100 cm3 of ethyl acetate and 100 cm of water are added and the reaction medium is filtered through a sinter funnel packed with Celite. The organic phase is separated out after settling of the phases has taken place, washed successively with 75 cm3 of water and with 75 cm3 of saturated sodium chloride solution, dried over magnesium sulphate, filtered and concentrated under reduced pressure (2 kPa; 50° C.) to give 1.6 g of an oil, which is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 3.5 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.) to give 700 mg of N-[5-(3-pyridyl)-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl])-1H-indazol-3-yl]butanamide in the form of a yellow oil.

Workup

  1. temperaturethe mixture is refluxed for 18 hours
  2. filtrationthe reaction medium is filtered through a sinter funnel
  3. customThe organic phase is separated out
  4. washwashed successively with 75 cm3 of water and with 75 cm3 of saturated sodium chloride solution
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure (2 kPa; 50° C.)

Sources & evidence

ORD record
ord-18bf42c2072347f4a6cdc99b16e7f20c
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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