Diisopropylamine → HCID 178452034, compound

HRID 2289053Notes

Reaction equation

HRID 2289053 reaction equation
C(N(CC)[CH:5]([CH3:7])[CH3:6])(C)C.[N+:10]([O-:13])(O)=[O:11].CC1C=C(C)[N:17]([C:21](N)=[NH:22])N=1.[NH2:24][CH2:25][CH2:26][C:27]([NH:29][C@H:30]1[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31]1)=[O:28].[CH:42](NC(C)C)(C)[CH3:43].[C:49]([O:52][CH2:53][CH3:54])(=[O:51])C>CN(C=O)C.ClCCl.O1CCCC1.CCOCC>[N+:10]([C:6]1[CH:5]=[CH:7][C:54]([CH2:53][O:52][C:49]([CH:25]([NH:24][C:21]([NH2:22])=[NH:17])[CH2:26][C:27]([NH:29][C@H:30]2[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31]2)=[O:28])=[O:51])=[CH:43][CH:42]=1)([O-:13])=[O:11]

Participants

10

Reactant 5

HCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 1981863,5-Dimethyl-1H-pyrazole-1-carboxamidine mononitrateHCID 571420191,1-Dimethylethyl (3S)-3-[(3-amino-1-oxopropyl)amino]-1-pyrrolidinecarboxylate

Product 1

HCID 178452034HCID 178452034, compound

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Under ice cooling, N,N-diisopropylethylamine (961 μl) and 3,5-dimethylpyrazole-1-carboxamidine nitrate (1.11 g) were added to a solution of tert-butyl (3S)-3-(3-aminopropanoylamino)-1-pyrrolidinecarboxylate (1.42 g) in anhydrous N,N'-dimethylformamide (10 ml) and the mixture was stirred overnight at room temperature. The reaction mixture was poured into ether (150 ml) to give an oily precipitate. The precipitate was dissolved in anhydrous dichloromethane:anhydrous tetrahydrofuran=5:2 (70 ml). To the resulting solution, a solution of N-(4-nitrobenzyloxycarbonyl)oxy-5-norbornene-2,3-dicarboxyimide (4.35 g) in anhydrous dichloromethane (35 ml) was added dropwise under ice cooling, followed by the addition of N,N-diisopropylamine (1.90 ml). The resulting mixture was stirred overnight. To the reaction mixture, ethyl acetate was added. The resulting mixture was washed with water and saturated saline, dried over anhydrous magnesium sulfate and concentrated by evaporation under reduced pressure. The residue was suspended in methanol (50 ml). To the suspension, a 1N aqueous sodium hydroxide solution (6 ml) was added under ice cooling, followed by stirring overnight. The reaction mixture was concentrated by evaporation under reduced pressure and the residue was dissolved in ethyl acetate. The resulting solution was washed with water and saturated saline, dried over anhydrous magnesium sulfate and concentrated by evaporation under reduced pressure. The residue was separated by chromatography through a silica gel column (ethyl acetate, ethyl acetate-methanol), whereby 955 mg of the title target compound were obtained.

Workup

  1. customto give an oily precipitate
  2. stirringThe resulting mixture was stirred overnight
  3. washThe resulting mixture was washed with water and saturated saline
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated by evaporation under reduced pressure
  6. additionTo the suspension, a 1N aqueous sodium hydroxide solution (6 ml) was added under ice cooling
  7. stirringby stirring overnight
  8. concentrationThe reaction mixture was concentrated by evaporation under reduced pressure
  9. dissolutionthe residue was dissolved in ethyl acetate
  10. washThe resulting solution was washed with water and saturated saline
  11. dry with materialdried over anhydrous magnesium sulfate
  12. concentrationconcentrated by evaporation under reduced pressure
  13. customThe residue was separated by chromatography through a silica gel column (ethyl acetate, ethyl acetate-methanol), whereby 955 mg of the title target compound
  14. customwere obtained

Sources & evidence

ORD record
ord-d40b31db01024e15b02c780a0492d95c
Source dataset
uspto-grants-2000_07
Patent number
US06090802

Reaction notes

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