1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-4-methyl-N-(4-benzyloxycarbonyl-2,6-dioxo-1-piperazinyl)valeramide

HRID 651784Notes

Reaction equation

HRID 651784 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][C:15](=[O:17])O[C:13](=[O:18])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:19]([O:23][C:24]([C@H:26]([C@@H:36]([CH2:41][CH:42]([CH3:44])[CH3:43])[C:37]([NH:39][NH2:40])=[O:38])[CH2:27]/[CH:28]=[CH:29]/[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:25])([CH3:22])([CH3:21])[CH3:20].Cl.C(N=C=NCCCN(C)C)C>ClCCl>[C:19]([O:23][C:24]([C@H:26]([C@@H:36]([CH2:41][CH:42]([CH3:44])[CH3:43])[C:37]([NH:39][N:40]1[C:13](=[O:18])[CH2:12][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])[CH2:16][C:15]1=[O:17])=[O:38])[CH2:27][CH:28]=[CH:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:25])([CH3:22])([CH3:21])[CH3:20]

Participants

5

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 54517630Benzyl 2,6-dioxomorpholine-4-carboxylateHCID 69709501(E)-2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-4-methylvalerohydrazide

Product 1

HCID 697117392(R)-[1(S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-4-methyl-N-(4-benzyloxycarbonyl-2,6-dioxo-1-piperazinyl)valeramideYield 70.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 0.7 g of 2,6-dioxo-4-morpholine carboxylic acid benzyl ester in 20 ml of dichloromethane was treated with 1.0 g of (E)-2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-4-methylvalerohydrazide (prepared as described in Example 1). The mixture was stirred for 1 hour at room temperature and then treated with 0.53 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride. The mixture was stirred for a further 3 hours at room temperature and then washed in sequence with 2M aqueous hydrogen chloride, 5% aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride. Drying of the organic phase over anhydrous magnesium sulphate and evaporation gave a residue which was purified by column chromatography on silica gel using ethyl acetate/ hexane (3:7) for the elution to give 1.16 g of 2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-4-methyl-N-(4-benzyloxycarbonyl-2,6-dioxo-1-piperazinyl)valeramide in the form of a white solid.

Workup

  1. stirringThe mixture was stirred for a further 3 hours at room temperature
  2. washwashed in sequence with 2M aqueous hydrogen chloride, 5% aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride
  3. dry with materialDrying of the organic phase over anhydrous magnesium sulphate and evaporation
  4. customgave a residue which
  5. customwas purified by column chromatography on silica gel
  6. washfor the elution

Sources & evidence

ORD record
ord-83520b4e75c543c2aa370aceb981b0cd
Source dataset
uspto-grants-2001_08
Patent number
US06281363B1

Reaction notes

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