2-Methoxy-5-(tributylstannyl)pyridine → 1-(4-Ethylpiperazin-1-yl)-3-(2-methoxypyridin-5-yl)isoquinoline

HRID 1814531Notes

Reaction equation

HRID 1814531 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([Sn](CCCC)(CCCC)CCCC)=[CH:5][N:4]=1.Br[C:23]1[N:24]=[C:25]([N:33]2[CH2:38][CH2:37][N:36]([CH2:39][CH3:40])[CH2:35][CH2:34]2)[C:26]2[C:31]([CH:32]=1)=[CH:30][CH:29]=[CH:28][CH:27]=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>[CH2:39]([N:36]1[CH2:35][CH2:34][N:33]([C:25]2[C:26]3[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:32]=[C:23]([C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[N:4][CH:5]=3)[N:24]=2)[CH2:38][CH2:37]1)[CH3:40]

Participants

5

Reactant 2

HCID 117290212-Methoxy-5-(tributylstannyl)pyridineHCID 225024471-(1-Ethylpiperazin-4-yl)-3-bromoisoquinoline

Product 1

HCID 225036721-(4-Ethylpiperazin-1-yl)-3-(2-methoxypyridin-5-yl)isoquinolineYield 61.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 7237O-XyleneSolvent

Procedure

2-Methoxy-5-tributylstannylpyridine (1.41 g) and 3-bromo-1-(4-ethylpiperazin-1-yl)isoquinoline (0.57 g) obtained in Example 28-2 were heated under reflux in the presence of tetrakistriphenylphosphinepalladium(0) (0.10 g) in xylene in nitrogen atmosphere for 30 min. After cooling, the reaction solution was filtered and extracted in 2N hydrochloric acid. The aqueous layer was washed with ethyl acetate twice. The resulting aqueous layer was 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, and the resulting residue was purified by silica gel column chromatography (chloroform/methanol system), to give 0.38 g of the free compound of the title compound as a pale brown powder.

Workup

  1. temperatureAfter cooling
  2. filtrationthe reaction solution was filtered
  3. extractionextracted in 2N hydrochloric acid
  4. washThe aqueous layer was washed with ethyl acetate twice
  5. extractionextracted 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-5c93b2b8c6554b95ac28f4cd00757a6d
Source dataset
uspto-grants-2005_04
Patent number
US06875761B2

Reaction notes

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