Triethylamine → trans-3-hydroxy-4-[(1H-imidazol-5-yl)carbonylamino]-N,N,gamma-trimethyl-alpha,alpha-diphenyl-1-piperidinebutanamide

HRID 981311Notes

Reaction equation

HRID 981311 reaction equation
C(N(CC)CC)C.[CH:8]1[N:9]=[CH:10][N:11]2[C:16]=1[C:15](=[O:17])[N:14]1C=N[CH:20]=[C:13]1[C:12]2=[O:21].N[C@@H]1C[CH2:27][N:26]([CH:29]([CH3:49])[CH2:30][C:31]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:32]([N:34]([CH3:36])[CH3:35])=[O:33])[CH2:25][C@H]1O>CN(C)C=O>[OH:21][C@H:12]1[C@H:13]([NH:14][C:15]([C:16]2[NH:11][CH:10]=[N:9][CH:8]=2)=[O:17])[CH2:20][CH2:27][N:26]([CH:29]([CH3:49])[CH2:30][C:31]([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)([C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[C:32]([N:34]([CH3:35])[CH3:36])=[O:33])[CH2:25]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1051510Diimidazo[1,5-a:1',5'-d]pyrazine-5,10-dioneHCID 67928771trans-4-amino-3-hydroxy-N,N,gamma-trimethyl-alpha,alpha-diphenyl-1-piperidinebutanamide

Product 1

HCID 86744578trans-3-hydroxy-4-[(1H-imidazol-5-yl)carbonylamino]-N,N,gamma-trimethyl-alpha,alpha-diphenyl-1-piperidinebutanamideYield 23%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2.8 Parts of N,N-diethylethanamine were added to a solution of 1 part of 5H, 10H-diimidazo[1,5-a:1',5'-d]pyrazine-5,10-dione in 36 parts of N,N-dimethylformamide. The thus obtained suspension was added dropwise to a stirred and heated (70° C.) solution of 3.95 parts of trans-4-amino-3-hydroxy-N,N,γ-trimethyl-α,α-diphenyl-1-piperidinebutanamide in 18 parts of N,N-dimethylformamide. Upon complete addition, stirring was continued overnight at 70° C. After evaporation, the residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (90:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was further purified by column chromatography (HPLC) over silica gel using a mixture of trichloromethane, methanol and methanol, saturated with ammonia, (90:9:1 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was pulverised and evaporated again, yielding 1.13 parts (23%) of trans-3-hydroxy-4-[(1H-imidazol-5-yl)carbonylamino] -N,N,γ-trimethyl-α,α-diphenyl-1-piperidinebutanamide; mp. 155.0° C. (compound 43).

Workup

  1. additionThe thus obtained suspension was added dropwise to
  2. additionUpon complete addition
  3. stirringstirring
  4. customAfter evaporation
  5. customthe residue was purified by column chromatography over silica gel using
  6. additiona mixture of trichloromethane and methanol
  7. customThe pure fractions were collected
  8. customthe eluent was evaporated
  9. customThe residue was further purified by column chromatography (HPLC) over silica gel using
  10. additiona mixture of trichloromethane, methanol and methanol
  11. customThe pure fractions were collected
  12. customthe eluent was evaporated
  13. customevaporated again

Sources & evidence

ORD record
ord-b6a491be0934422c9fd8e464ed95824e
Source dataset
uspto-grants-1991_02
Patent number
US04990521

Reaction notes

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