1-(1-Ethylpiperazin-4-yl)-3-bromoisoquinoline → 1-(4-ethylpiperazin-1-yl)-3-[4-[N-(2-benzyloxyethyl)sulfamoyl]phenyl)isoquinoline

HRID 1006979Notes

Reaction equation

HRID 1006979 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][NH:11][S:12]([C:15]1[CH:20]=[CH:19][C:18]([Sn](CCCC)(CCCC)CCCC)=[CH:17][CH:16]=1)(=[O:14])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:35]1[N:36]=[C:37]([N:45]2[CH2:50][CH2:49][N:48]([CH2:51][CH3:52])[CH2:47][CH2:46]2)[C:38]2[C:43]([CH:44]=1)=[CH:42][CH:41]=[CH:40][CH:39]=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>[CH2:51]([N:48]1[CH2:47][CH2:46][N:45]([C:37]2[C:38]3[C:43](=[CH:42][CH:41]=[CH:40][CH:39]=3)[CH:44]=[C:35]([C:18]3[CH:17]=[CH:16][C:15]([S:12](=[O:13])(=[O:14])[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:20][CH:19]=3)[N:36]=2)[CH2:50][CH2:49]1)[CH3:52]

Participants

5

Reactant 2

HCID 225024471-(1-Ethylpiperazin-4-yl)-3-bromoisoquinolineHCID 69183332N-(2-Benzyloxyethyl)4-tributylstannylbenzenesulfonamide

Product 1

HCID 225032411-(4-ethylpiperazin-1-yl)-3-[4-[N-(2-benzyloxyethyl)sulfamoyl]phenyl)isoquinolineYield 48.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 7237O-XyleneSolvent

Procedure

N-(2-Benzyloxyethyl)4-tributylstannylbenzenesulfonamide (0.92 g) and 3-bromo-1-(4-ethylpiperazin-1-yl)isoquinoline (0.42 g) were heated under reflux in the presence of tetrakistriphenylphosphinepalladium(0) (0.09 g) in xylene in nitrogen atmosphere for 45 min. After cooling, the reaction solution was filtered and concentrated. The 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)sulfamoyl]phenyl}isoquinoline (0.34 g) as a pale brown oil.

Workup

  1. temperatureAfter cooling
  2. filtrationthe reaction solution was filtered
  3. concentrationconcentrated
  4. customThe 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-d1a88243b3984d718f3f34451d7064ca
Source dataset
uspto-grants-2004_09
Patent number
US06790844B2

Reaction notes

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