1-(1-Ethylpiperazin-4-yl)-3-bromoisoquinoline → HCID 22503385, compound

HRID 1006998Notes

Reaction equation

HRID 1006998 reaction equation
[CH3:1][N:2]([CH2:24][CH2:25][O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:3](=[O:23])[C:4]1[CH:9]=[CH:8][C:7]([Sn](CCCC)(CCCC)CCCC)=[CH:6][CH:5]=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:7]3[CH:6]=[CH:5][C:4]([C:3](=[O:23])[N:2]([CH2:24][CH2:25][O:26][CH2:27][C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH3:1])=[CH:9][CH:8]=3)[N:36]=2)[CH2:50][CH2:49]1)[CH3:52]

Participants

6

Reactant 2

HCID 225024471-(1-Ethylpiperazin-4-yl)-3-bromoisoquinolineHCID 22503653HCID 22503653, compound

Product 1

HCID 22503385HCID 22503385, compoundYield 46.7%

Reagents, catalysts & solvents 3

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

Procedure

N-Methyl-N-(2-benzyloxyethyl)-4-tributylstannylbenzamide (1.93 g) and 3-bromo-1-(4-ethylpiperazin-1-yl)isoquinoline (0.93 g) were heated under reflux overnight in the presence of tetrakistriphenylphosphinepalladium(0) (0.13 g) in xylene in nitrogen atmosphere. After cooling, the reaction solution was diluted with ethyl acetate and filtered. The filtrate was extracted with 2N hydrochloric acid. The aqueous layer was washed with ethyl acetate and adjusted to pH 10 by a 8N aqueous solution of sodium hydroxide, which was then extracted with ethyl acetate, washed with a 10% aqueous solution of sodium carbonate and brine, and then 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-[N-(2-benzyloxyethyl)-N-methylcarbamoyl]phenyl}isoquinoline (0.69 g) as a pale yellow viscous oil.

Workup

  1. temperatureAfter cooling
  2. filtrationfiltered
  3. extractionThe filtrate was extracted with 2N hydrochloric acid
  4. washThe aqueous layer was washed with ethyl acetate
  5. extractionwas then extracted 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
  9. customthe resulting residue was purified by silica gel column chromatography (chloroform/methanol system)

Sources & evidence

ORD record
ord-3c056bf9b46e44508863b627892273d0
Source dataset
uspto-grants-2004_09
Patent number
US06790844B2

Reaction notes

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