1-(1-Ethylpiperazin-4-yl)-3-bromoisoquinoline → HCID 22503313, compound

HRID 1006984Notes

Reaction equation

HRID 1006984 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][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.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>[CH2:51]([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]([CH2:11][CH2:10][CH2:9][O:8][CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)(=[O:13])=[O:14])=[CH:20][CH:19]=3)[N:36]=2)[CH2:50][CH2:49]1)[CH3:52]

Participants

6

Reactant 2

HCID 225024471-(1-Ethylpiperazin-4-yl)-3-bromoisoquinolineHCID 22503169HCID 22503169, compound

Product 1

HCID 22503313HCID 22503313, compoundYield 72.7%

Reagents, catalysts & solvents 3

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

Procedure

(4-Tributylstannylphenyl) (3-benzyloxypropyl) sulfone (5.78 g) and 3-bromo-1-(4-ethylpiperazin-1-yl)isoquinoline (2.13 g) were heated under reflux in the presence of tetrakistriphenylphosphinepalladium(0) (0.58 g) in xylene in nitrogen atmosphere for 7 hr. 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 and adjusted to pH 10 with a 8N aqueous solution of sodium hydroxide, which was 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 (chloroform/methanol system), to give 1-(4-ethylpiperazin-1-yl)-3-[4-(3-benzyloxypropyl)sulfonylphenyl]isoquinoline (2.56 g) as a pale brown amorphous.

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. extractionwas then extracted 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 (chloroform/methanol system)

Sources & evidence

ORD record
ord-71f9e899f37f4ad08f5044d423ed1f22
Source dataset
uspto-grants-2004_09
Patent number
US06790844B2

Reaction notes

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