1-(1-Ethylpiperazin-4-yl)-3-bromoisoquinoline → 1-(4-Ethylpiperazin-1-yl)-3-[4-(3-oxobutyl)phenyl]isoquinoline

HRID 1007004Notes

Reaction equation

HRID 1007004 reaction equation
C([Sn](CCCC)(CCCC)[C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][C:14](=[O:16])[CH3:15])=[CH:8][CH:7]=1)CCC.Br[C:26]1[N:27]=[C:28]([N:36]2[CH2:41][CH2:40][N:39]([CH2:42][CH3:43])[CH2:38][CH2:37]2)[C:29]2[C:34]([CH:35]=1)=[CH:33][CH:32]=[CH:31][CH:30]=2>C1(C)C(C)=CC=CC=1.C(OCC)(=O)C.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>[CH2:42]([N:39]1[CH2:38][CH2:37][N:36]([C:28]2[C:29]3[C:34](=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH:35]=[C:26]([C:6]3[CH:7]=[CH:8][C:9]([CH2:12][CH2:13][C:14](=[O:16])[CH3:15])=[CH:10][CH:11]=3)[N:27]=2)[CH2:41][CH2:40]1)[CH3:43]

Participants

6

Reactant 2

HCID 225024471-(1-Ethylpiperazin-4-yl)-3-bromoisoquinolineHCID 225026514-(4-Tributylstannylphenyl)-2-butanone

Product 1

HCID 225031951-(4-Ethylpiperazin-1-yl)-3-[4-(3-oxobutyl)phenyl]isoquinolineYield 62.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 7237O-XyleneSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-(4-Tributylstannylphenyl)-2-butanone (2.46 g) and 3-bromo-1-(4-ethylpiperazin-1-yl)isoquinoline (1.41 g) were heated under reflux in the presence of tetrakistriphenylphosphinepalladium(0) (0.22 g) in xylene in nitrogen atmosphere overnight. After cooling, the reaction solution was diluted with ethyl acetate and filtered. The filtrate was extracted in 2N hydrochloric acid, and the resulting aqueous layer was washed with ethyl acetate, adjusted to pH 10 with a 8N aqueous solution of sodium hydroxide, and then extracted with ethyl acetate. The extract was washed with a 10% aqueous solution of sodium carbonate and brine, and dried over magnesium sulfate. The solvent was evaporated, and the resulting residue was purified by silica gel column chromatography (toluene/acetone system), to give 1-(4-ethylpiperazin-1-yl)-3-[4-(3-oxobutyl)phenyl]isoquinoline (1.07 g) as a pale yellow viscous oil.

Workup

  1. temperatureAfter cooling
  2. filtrationfiltered
  3. extractionThe filtrate was extracted in 2N hydrochloric acid
  4. washthe resulting aqueous layer was washed with ethyl acetate
  5. extractionextracted with ethyl acetate
  6. washThe extract was washed with a 10% aqueous solution of sodium carbonate and brine
  7. dry with materialdried over magnesium sulfate
  8. customThe solvent was evaporated
  9. customthe resulting residue was purified by silica gel column chromatography (toluene/acetone system)

Sources & evidence

ORD record
ord-43916cbf2e3e4ae8882bfa23b69c924a
Source dataset
uspto-grants-2004_09
Patent number
US06790844B2

Reaction notes

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