Dimethylformamide → 9-phenylpropyl-7-methoxy-1-methyl-beta-carboline

HRID 1619467Notes

Reaction equation

HRID 1619467 reaction equation
[C:1]1([C:16]2[NH:15][C:14]3[C:7](=[CH:8][CH:9]=[C:10]([CH:13]=3)[O:11][CH3:12])[C:6]=2[CH:5]=[CH:4][N:3]=1)[CH3:2].CN(C=O)C.[H-].[Na+].C([O-])(O)=O.[Na+]>C(OCC)(=O)C.O.C1COCC1>[C:7]1([CH2:6][CH2:5][CH2:4][N:15]2[C:16]3[C:1]([CH3:2])=[N:3][CH:4]=[CH:5][C:6]=3[C:7]3[C:14]2=[CH:13][C:10]([O:11][CH3:12])=[CH:9][CH:8]=3)[CH:14]=[CH:13][CH:10]=[CH:9][CH:8]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 5280953Harmine

Product 1

HCID 116528419-phenylpropyl-7-methoxy-1-methyl-beta-carbolineYield 101.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Harmine 1 (0.53 g, 2.5 mmol), DMF (15 ml) and THF (15 ml) were respectively added in a 100 ml round-bottom flask, and stirred at room temperature until the mixture became clear, then 60% NaH (0.3 g, 7.5 mol) was added and stirred until there were no bubbles formed. 1-Brombenzenepropropane (2 ml) was added dropwise. The mixture was refluxed for 12 h. THF was evaporated in reduced pressure. The residues were poured into 30 ml cold water and extracted with ethyl acetate. The organic phases were combined, and washed with water and brine, dried over anhydrous sodium sulfate, filtered, evaporated in reduced pressure, and the residue dissolved in 50 anhydrous ethanol. The pH was adjusted to 4 with concentrated HCl, the mixture were concentrated in vacuum and then recrystallized with acetone to afford yellow solids. The solids were dissolved into a mixed solution of water and ethyl acetate. The pH was adjusted to 8 with saturated NaHCO3 solution. The organic layer was isolated, and the aqueous phase was extracted with ethyl acetate. The organic phases were combined, washed with water and brine, dried over anhydrous sodium sulfate, decolorized with activated carbon, filtered, concentrated, and recrystallized with ethyl ether to afford gray needle crystals (0.42 g, 51%), mp 117-118° C.

Workup

  1. stirringstirred until there
  2. customformed
  3. addition1-Brombenzenepropropane (2 ml) was added dropwise
  4. temperatureThe mixture was refluxed for 12 h
  5. customTHF was evaporated in reduced pressure
  6. additionThe residues were poured into 30 ml cold water
  7. extractionextracted with ethyl acetate
  8. washwashed with water and brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. customevaporated in reduced pressure
  12. dissolutionthe residue dissolved in 50 anhydrous ethanol
  13. concentrationthe mixture were concentrated in vacuum
  14. customrecrystallized with acetone
  15. customto afford yellow solids
  16. customThe organic layer was isolated
  17. extractionthe aqueous phase was extracted with ethyl acetate
  18. washwashed with water and brine
  19. dry with materialdried over anhydrous sodium sulfate
  20. filtrationfiltered
  21. concentrationconcentrated
  22. customrecrystallized with ethyl ether

Sources & evidence

ORD record
ord-4a7c3e88182d458b87bce88f232989a0
Source dataset
uspto-grants-2014_07
Patent number
US08772311B2

Reaction notes

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