Sodium hydride → (E)-allyl-[4-[1-(4-bromo-phenyl)-isoquinolin-6-yloxy]-but-2-enyl]-methyl-amine

HRID 342218Notes

Reaction equation

HRID 342218 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([OH:18])=[CH:15][CH:16]=3)[CH:11]=[CH:10][N:9]=2)=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:22]/[CH:23]=[CH:24]/[CH2:25]Br.[CH2:27]([NH:30][CH3:31])[CH:28]=[CH2:29]>CN(C=O)C>[CH2:27]([N:30]([CH2:22]/[CH:23]=[CH:24]/[CH2:25][O:18][C:14]1[CH:13]=[C:12]2[C:17](=[CH:16][CH:15]=1)[C:8]([C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=1)=[N:9][CH:10]=[CH:11]2)[CH3:31])[CH:28]=[CH2:29]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 69391N-MethylallylamineHCID 641245trans-1,4-Dibromo-2-buteneHCID 1361286691-(4-Bromo-phenyl)-isoquinolin-6-ol

Product 1

HCID 67598888(E)-allyl-[4-[1-(4-bromo-phenyl)-isoquinolin-6-yloxy]-but-2-enyl]-methyl-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of 0.5 g of 1-(4-bromo-phenyl)-isoquinolin-6-ol in 15 ml of DMF is cooled to 0° C. and treated with 0.15 g of ~55% sodium hydride. The mixture is stirred for 40 min., with a solution resulting. A solution of 0.39 g of (E)-1,4-dibromo-2-butene in 5 ml of DMF is added dropwise at -20° C. After stirring at -15° to -20° C. for 3 hrs. 0.8 ml of N-allyl-methyl-amine is added, the mixture is stirred overnight and warmed to room temperature. Subsequently, the reaction mixture is concentrated and the residue is treated with sodium hydrogen carbonate solution and extracted with methylene chloride. The organic extracts are washed with saturated sodium chloride solution, dried over sodium sulphate and concentrated. The residue is chromatographed with toluene/acetone/triethylamine (90:9:1 to 70:29:1). There is obtained 0.1 g of (E)-allyl-[4-[1-(4-bromo-phenyl)-isoquinolin-6-yloxy]-but-2-enyl]-methyl-amine which is converted into the fumarate, MS: m/e 423 (M+H+, 1 Br).

Workup

  1. customresulting
  2. stirringAfter stirring at -15° to -20° C. for 3 hrs
  3. stirringthe mixture is stirred overnight
  4. temperaturewarmed to room temperature
  5. concentrationSubsequently, the reaction mixture is concentrated
  6. additionthe residue is treated with sodium hydrogen carbonate solution
  7. extractionextracted with methylene chloride
  8. washThe organic extracts are washed with saturated sodium chloride solution
  9. dry with materialdried over sodium sulphate
  10. concentrationconcentrated
  11. customThe residue is chromatographed with toluene/acetone/triethylamine (90:9:1 to 70:29:1)

Sources & evidence

ORD record
ord-18e2085df2d24afb8f6098528773eb7e
Source dataset
uspto-grants-1999_01
Patent number
US05856503

Reaction notes

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