1-(1-Ethylpiperazin-4-yl)-3-bromoisoquinoline → HCID 22503411, compound

HRID 1006977Notes

Reaction equation

HRID 1006977 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][NH:11][C:12](=[O:32])[C:13]1[CH:18]=[CH:17][C:16]([Sn](CCCC)(CCCC)CCCC)=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:34]1[N:35]=[C:36]([N:44]2[CH2:49][CH2:48][N:47]([CH2:50][CH3:51])[CH2:46][CH2:45]2)[C:37]2[C:42]([CH:43]=1)=[CH:41][CH:40]=[CH:39][CH:38]=2>C1(C)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>[CH2:50]([N:47]1[CH2:46][CH2:45][N:44]([C:36]2[C:37]3[C:42](=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH:43]=[C:34]([C:16]3[CH:15]=[CH:14][C:13]([C:12](=[O:32])[NH:11][CH2:10][CH2:9][O:8][CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)=[CH:18][CH:17]=3)[N:35]=2)[CH2:49][CH2:48]1)[CH3:51]

Participants

5

Reactant 2

HCID 225024471-(1-Ethylpiperazin-4-yl)-3-bromoisoquinolineHCID 22503540HCID 22503540, compound

Product 1

HCID 22503411HCID 22503411, compoundYield 22.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 7237O-XyleneSolvent

Procedure

N-(2-Benzyloxyethyl)-4-tributylstannylbenzamide (1.23 g) and 3-bromo-1-(4-ethylpiperazin-1-yl)isoquinoline (0.49 g) were heated under reflux in the presence of tetrakistriphenylphosphinepalladium(0) (0.13 g) in xylene in nitrogen atmosphere for 3 hr. After cooling, the reaction solution was filtered and concentrated. The resulting residue was purified by silica gel column chromatography (chloroform/methanol system). The resulting product was dissolved in ethyl acetate and extracted with 2N hydrochloric acid. The 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, to give 1-(4-ethylpiperazin-1-yl)-3-{4-[N-(2-benzyloxyethyl)carbamoyl]phenyl}isoquinoline (0.17 g) as a pale brown viscous oil.

Workup

  1. temperatureAfter cooling
  2. filtrationthe reaction solution was filtered
  3. concentrationconcentrated
  4. customThe resulting residue was purified by silica gel column chromatography (chloroform/methanol system)
  5. dissolutionThe resulting product was dissolved in ethyl acetate
  6. extractionextracted with 2N hydrochloric acid
  7. washThe aqueous layer was washed with ethyl acetate
  8. extractionextracted with ethyl acetate
  9. washThe extract was washed with a 10% aqueous solution of sodium carbonate and brine
  10. dry with materialdried over magnesium sulfate
  11. customThe solvent was evaporated

Sources & evidence

ORD record
ord-610755ac53dc40228b09f3a96e96eb95
Source dataset
uspto-grants-2004_09
Patent number
US06790844B2

Reaction notes

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