1-(1-Ethylpiperazin-4-yl)-3-bromoisoquinoline → HCID 178462710, compound

HRID 1814573Notes

Reaction equation

HRID 1814573 reaction equation
[C:1]([O:4][C@H:5]1[CH2:10][CH2:9][C@H:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[Sn](CCCC)(CCCC)CCCC)[CH2:7][CH2:6]1)(=[O:3])[CH3:2].Br[C:31]1[N:32]=[C:33]([N:41]2[CH2:46][CH2:45][N:44]([CH2:47][CH3:48])[CH2:43][CH2:42]2)[C:34]2[C:39]([CH:40]=1)=[CH:38][CH:37]=[CH:36][CH:35]=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>[CH2:47]([N:44]1[CH2:43][CH2:42][N:41]([C:33]2[C:34]3[C:39](=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH:40]=[C:31]([C:14]3[CH:13]=[CH:12][C:11]([C@H:8]4[CH2:7][CH2:6][C@H:5]([O:4][C:1](=[O:3])[CH3:2])[CH2:10][CH2:9]4)=[CH:16][CH:15]=3)[N:32]=2)[CH2:46][CH2:45]1)[CH3:48]

Participants

6

Reactant 2

HCID 225024471-(1-Ethylpiperazin-4-yl)-3-bromoisoquinolineHCID 178448214HCID 178448214, compound

Product 1

HCID 178462710HCID 178462710, compoundYield 87.1%

Reagents, catalysts & solvents 3

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

Procedure

Trans-4-(tributylstannylphenyl)cyclohexyl acetate (0.56 g) and 3-bromo-1-(4-ethylpiperazin-1-yl)isoquinoline (0.46 g) were heated under reflux in the presence of tetrakistriphenylphosphinepalladium(0) (0.06 g) in xylene in nitrogen atmosphere overnight. After cooling, the reaction solution was diluted with ethyl acetate and filtered. The filtrate was extracted with 2N hydrochloric acid, and the resulting aqueous layer was washed with ethyl acetate. Then, it was adjusted to pH 10 by a 8N aqueous solution of sodium hydroxide, extracted with ethyl acetate, washed with a 10% aqueous solution of sodium carbonate and brine, and dried over magnesium sulfate. The solvent was evaporated, to give a mixture (0.44 g) of 1-(4-ethylpiperazin-1-yl)-3-[4-(trans-4-acetoxycyclohexyl)phenyl]isoquinoline as a brown viscous oil and the starting material.

Workup

  1. temperatureAfter cooling
  2. filtrationfiltered
  3. extractionThe filtrate was extracted with 2N hydrochloric acid
  4. washthe resulting aqueous layer was washed with ethyl acetate
  5. extractionextracted with ethyl acetate
  6. washwashed with a 10% aqueous solution of sodium carbonate and brine
  7. dry with materialdried over magnesium sulfate
  8. customThe solvent was evaporated

Sources & evidence

ORD record
ord-1299bc7d8dad47e1b29e72b49d7edde0
Source dataset
uspto-grants-2005_04
Patent number
US06875761B2

Reaction notes

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