Triethylamine → (3R,6R)-1-benzyl-3-(N-formyl-1H-indol-3-yl-methyl)-6-methylpiperazine-2,5-dione

HRID 1418554Notes

Reaction equation

HRID 1418554 reaction equation
N#N.C(O[C:8]([NH:10][C@@H:11]([C:24]([OH:26])=O)[CH2:12][C:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]([CH:22]=[O:23])[CH:14]=1)=[O:9])(C)(C)C.Cl.[CH2:28]([NH:35][C@H:36](C)[C:37](OCC1C=CC=CC=1)=O)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C(N(CC)CC)C.[I-].ClC1C=CC=C[N+]=1C>ClCCl>[CH2:28]([N:35]1[C@H:36]([CH3:37])[C:8](=[O:9])[NH:10][C@H:11]([CH2:12][C:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]([CH:22]=[O:23])[CH:14]=2)[C:24]1=[O:26])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 1670692-Chloro-1-methylpyridinium iodideHCID 86751286N2 (tert-butoxycarbonyl)-N1-formyl-D-tryptophanHCID 86751287benzyl (2R)-2-(N-benzylamino)propionate hydrochloride

Product 1

HCID 54152748(3R,6R)-1-benzyl-3-(N-formyl-1H-indol-3-yl-methyl)-6-methylpiperazine-2,5-dioneYield 57.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of N2 -(tert-butoxycarbonyl)-N1 -formyl-D-tryptophan (2.17 g) and benzyl (2R)-2-(N-benzylamino)propionate hydrochloride (2.0 g) in dichloromethane (30 ml) was added triethylamine (2.3 ml) under nitrogen atmosphere. To the mixture was added 2-chloro-1-methylpyridinium iodide (1.84 g) at room temperature, and the resulting mixture was stirred for 2 hours and left overnight. The reaction mixture was washed successively with dilute hydrochloric acid, aqueous sodium bicarbonate solution and brine, and dried over magnesium sulfate. After evaporation of the solvent, the residue was dissolved in dichloromethane (30 ml). A solution of 4N hydrogen chloride in dioxane solution (10 ml) was added thereto at ice-bath temperature and-then the resulting mixture was stirred for 1 hour at room temperature. The reaction mixture was concentrated under reduced pressure. The residue was partitioned between dichloromethane and aqueous saturated sodium bicarbonate solution. The organic layer was separated, washed with brine, dried over magnesium sulfate and filtered. To the filtrate was added triethylamine (1 ml) and the resulting mixture was stirred for 1 hour at room temperature. The reaction mixture was concentrated under reduced pressure. The residue was purified on a silica gel column (60 g) eluting with a mixture of n-hexane and ethyl acetate (2:1) to give (3R,6R)-1-benzyl-3-(N-formyl-1H-indol-3-yl-methyl)-6-methylpiperazine-2,5-dione (1.3 g).

Workup

  1. waitleft overnight
  2. washThe reaction mixture was washed successively with dilute hydrochloric acid, aqueous sodium bicarbonate solution and brine
  3. dry with materialdried over magnesium sulfate
  4. customAfter evaporation of the solvent
  5. dissolutionthe residue was dissolved in dichloromethane (30 ml)
  6. additionA solution of 4N hydrogen chloride in dioxane solution (10 ml) was added
  7. stirringat ice-bath temperature and-then the resulting mixture was stirred for 1 hour at room temperature
  8. concentrationThe reaction mixture was concentrated under reduced pressure
  9. customThe residue was partitioned between dichloromethane and aqueous saturated sodium bicarbonate solution
  10. customThe organic layer was separated
  11. washwashed with brine
  12. dry with materialdried over magnesium sulfate
  13. filtrationfiltered
  14. additionTo the filtrate was added triethylamine (1 ml)
  15. stirringthe resulting mixture was stirred for 1 hour at room temperature
  16. concentrationThe reaction mixture was concentrated under reduced pressure
  17. customThe residue was purified on a silica gel column (60 g)
  18. washeluting with a mixture of n-hexane and ethyl acetate (2:1)

Sources & evidence

ORD record
ord-b141b5fa6a7344fe871fce9a9f129f3e
Source dataset
uspto-grants-1999_03
Patent number
US05883098

Reaction notes

Loading…