Sodium Carbonate → 1-(4-Ethylpiperazin-1-yl)-3-[4-(2-benzyloxyethyl)phenyl]isoquinoline

HRID 1006982Notes

Reaction equation

HRID 1006982 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14](OB(O)O)=[CH:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:22]1[N:23]=[C:24]([N:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH3:39])[CH2:34][CH2:33]2)[C:25]2[C:30]([CH:31]=1)=[CH:29][CH:28]=[CH:27][CH:26]=2.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.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>[CH2:38]([N:35]1[CH2:34][CH2:33][N:32]([C:24]2[C:25]3[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:31]=[C:22]([C:14]3[CH:15]=[CH:16][C:11]([CH2:10][CH2:9][O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:12][CH:13]=3)[N:23]=2)[CH2:37][CH2:36]1)[CH3:39]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 225024471-(1-Ethylpiperazin-4-yl)-3-bromoisoquinolineHCID 225024564-(2-Benzyloxyethyl)phenylboric acid3×

Product 1

HCID 177943201-(4-Ethylpiperazin-1-yl)-3-[4-(2-benzyloxyethyl)phenyl]isoquinolineYield 72.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

4-(2-Benzyloxyethyl)phenylboric acid (0.40 g) and 3-bromo-1-(4-ethylpiperazin-1-yl)isoquinoline (0.65 g) were heated under reflux in the presence of tetrakistriphenylphosphinepalladium(0) (0.09 g) in toluene (50 ml) and a 10% aqueous solution of sodium carbonate (30 ml) in nitrogen atmosphere for 1 hr. To the mixture was additionally added 4-(2-benzyloxyethyl)phenylboric acid (0.40 g), and the mixture was heated under reflux for 1.5 hr. 4-(2-Benzyloxyethyl)phenylboric acid (0.40 g) was again added, and the mixture was heated under reflux overnight. The organic layer was separated, and it was extracted with 2N hydrochloric acid twice. The resulting aqueous layer was washed with ethyl acetate, adjusted to pH 10 with a 8N aqueous solution of sodium hydroxide, extracted with ethyl acetate, washed with a 10% aqueous solution of sodium carbonate and brine, and then dried over magnesium sulfate. The solvent was evaporated, and the resulting residue was purified by silica gel column chromatography (chloroform/methanol system, and then ethyl acetate/acetone system), to give 1-(4-ethylpiperazin-1-yl)-3-[4-(2-benzyloxyethyl)phenyl]isoquinoline (0.48 g) as a colorless viscous oil.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 1.5 hr
  3. temperaturethe mixture was heated
  4. temperatureunder reflux overnight
  5. customThe organic layer was separated
  6. extractionit was extracted with 2N hydrochloric acid twice
  7. washThe resulting aqueous layer was washed with ethyl acetate
  8. extractionextracted with ethyl acetate
  9. washwashed with a 10% aqueous solution of sodium carbonate and brine
  10. dry with materialdried over magnesium sulfate
  11. customThe solvent was evaporated
  12. customthe resulting residue was purified by silica gel column chromatography (chloroform/methanol system

Sources & evidence

ORD record
ord-7879f7bdfcfc4845bc11b5f5def031ea
Source dataset
uspto-grants-2004_09
Patent number
US06790844B2

Reaction notes

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