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

HRID 1619466Notes

Reaction equation

HRID 1619466 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+].[CH2:24](Br)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>C1COCC1>[CH2:24]([N:15]1[C:16]2[C:1]([CH3:2])=[N:3][CH:4]=[CH:5][C:6]=2[C:7]2[C:14]1=[CH:13][C:10]([O:11][CH3:12])=[CH:9][CH:8]=2)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 5280953Harmine

Product 1

HCID 99483409-benzyl-7-methoxy-1-methyl-beta-carbolineYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Harmine 1 (2.1 g, 10 mmol), DMF (50 ml) and THF (50 ml) were respectively added in a 250 ml round-bottom flask, and were stirred at room temperature for 10 minutes followed by the addition of 60% NaH (1.2 g, 30 mmol). The mixture was stirred until there were no bubbles formed. Benzyl bromide (3 ml) was added dropwise. The mixture was then refluxed by heating for 8 h. THF was evaporated in reduced pressure, and the residues were poured into cold water. The mixture was adjusted to pH 3.0 with concentrated HCl, and extracted with ethyl ether. The aqueous phase was neutralized (pH8) with saturated NaHCO3 solution and extracted with ethyl acetate. The organic phases were combined, washed with water and brine, dried over anhydrous sodium sulfate, filtered, evaporated in reduced pressure and then recrystallized with ethyl acetate to afford gray crystals (2.2 g, 67%). mp 131-133° C.

Workup

  1. stirringThe mixture was stirred until there
  2. customformed
  3. temperatureThe mixture was then refluxed
  4. temperatureby heating for 8 h
  5. customTHF was evaporated in reduced pressure
  6. additionthe residues were poured into cold water
  7. extractionextracted with ethyl ether
  8. extractionextracted with ethyl acetate
  9. washwashed with water and brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. customevaporated in reduced pressure
  13. customrecrystallized with ethyl acetate

Sources & evidence

ORD record
ord-26f706e21b7449f684bae1fa89411af2
Source dataset
uspto-grants-2014_07
Patent number
US08772311B2

Reaction notes

Loading…