HCID 67586227, compound → (4-nitrophenyl)methyl (2S,4S)-4-[(4-methoxyphenyl)methylsulfanyl]-2-[4-[N-[(4-nitrophenyl)methoxycarbonyl]carbamimidoyl]piperazine-1-carbonyl]pyrrolidine-1-carboxylate

HRID 362102Notes

Reaction equation

HRID 362102 reaction equation
[CH3:1][O:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][S:8][C@@H:9]2[CH2:13][N:12](OCC3C=CC([N+]([O-])=O)=CC=3)[C@H:11]([C:25]([OH:27])=O)[CH2:10]2)=[CH:5][CH:4]=1.[N+:30]([C:33]1[CH:51]=[CH:50][C:36]([CH2:37][O:38][C:39]([NH:41][C:42]([N:44]2[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]2)=[NH:43])=[O:40])=[CH:35][CH:34]=1)([O-:32])=[O:31]>C(#N)C.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][S:8][C@@H:9]2[CH2:13][N:12]([C:39]([O:38][CH2:37][C:36]3[CH:35]=[CH:34][C:33]([N+:30]([O-:32])=[O:31])=[CH:51][CH:50]=3)=[O:40])[C@H:11]([C:25]([N:47]3[CH2:46][CH2:45][N:44]([C:42](=[NH:43])[NH:41][C:39]([O:38][CH2:37][C:36]4[CH:35]=[CH:34][C:33]([N+:30]([O-:32])=[O:31])=[CH:51][CH:50]=4)=[O:40])[CH2:49][CH2:48]3)=[O:27])[CH2:10]2)=[CH:28][CH:29]=1

Participants

5

Reactant 2

HCID 67586227HCID 67586227, compoundHCID 140386412(4-Nitrophenyl)methyl [imino(piperazin-1-yl)methyl]carbamate

Product 1

HCID 141564120(4-nitrophenyl)methyl (2S,4S)-4-[(4-methoxyphenyl)methylsulfanyl]-2-[4-[N-[(4-nitrophenyl)methoxycarbonyl]carbamimidoyl]piperazine-1-carbonyl]pyrrolidine-1-carboxylateYield 141.6%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

740 mg of (2S,4S)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxy)pyrrolidine-2-carboxylic acid was dissolved in 7.4 ml of dry acetonitrile, and 330 mg of N,N'-carbonyldiimidazole were added to the resulting solution, after which the mixture was stirred at room temperature for 30 minutes. At the end of this time, a solution of 525 mg of 1-(4-nitrobenzyloxycarbonylamidino)piperazine [prepared as described in step (c) above] dissolved in 10 ml of acetonitrile was added to the resulting mixture, and the mixture was left to stand overnight under the same conditions. The reaction mixture was then diluted with ethyl acetate, after which it was washed with an aqueous solution of sodium hydrogencarbonate, with water and with an aqueous solution of sodium chloride, in that order, dried over anhydrous sodium sulfate and concentrated by evaporation under reduced pressure. The resulting residue was subjected to silica gel column chromatography, eluted first with ethyl acetate alone and then with a 4:1 by volume mixture of ethyl acetate and acetonitrile, in that order. The fractions containing the desired compound were concentrated by evaporation under reduced pressure, to obtain 890 mg of the title compound, as a powder.

Workup

  1. additionwas added to the resulting mixture
  2. waitthe mixture was left
  3. waitto stand overnight under the same conditions
  4. washafter which it was washed with an aqueous solution of sodium hydrogencarbonate, with water and with an aqueous solution of sodium chloride, in that order
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated by evaporation under reduced pressure
  7. washeluted first with ethyl acetate alone
  8. additionwith a 4:1 by volume mixture of ethyl acetate and acetonitrile
  9. additionThe fractions containing the desired compound
  10. concentrationwere concentrated by evaporation under reduced pressure

Sources & evidence

ORD record
ord-0fe7ed629de8497182872468ed605dd3
Source dataset
uspto-grants-1999_02
Patent number
US05866564

Reaction notes

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