Diisopropylethylamine → (4-nitrophenyl)methyl N-[4-[(2S,4S)-4-[(4-methoxyphenyl)methylsulfanyl]-1-methylpyrrolidine-2-carbonyl]piperazine-1-carboximidoyl]carbamate

HRID 727722Notes

Reaction equation

HRID 727722 reaction equation
[CH3:1][O:2][C:3]1[CH:19]=[CH:18][C:6]([CH2:7][S:8][C@@H:9]2[CH2:13][N:12]([CH3:14])[C@H:11]([C:15]([OH:17])=O)[CH2:10]2)=[CH:5][CH:4]=1.FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[N+:34]([C:37]1[CH:55]=[CH:54][C:40]([CH2:41][O:42][C:43]([NH:45][C:46]([N:48]2[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]2)=[NH:47])=[O:44])=[CH:39][CH:38]=1)([O-:36])=[O:35].C(N(C(C)C)CC)(C)C>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]([CH3:14])[C@H:11]([C:15]([N:51]3[CH2:52][CH2:53][N:48]([C:46](=[NH:47])[NH:45][C:43]([O:42][CH2:41][C:40]4[CH:39]=[CH:38][C:37]([N+:34]([O-:36])=[O:35])=[CH:55][CH:54]=4)=[O:44])[CH2:49][CH2:50]3)=[O:17])[CH2:10]2)=[CH:18][CH:19]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 15297072HCID 15297072, compoundHCID 140386409(4-nitrophenyl)methyl N-(piperazine-1-carboximidoyl)carbamate;bis(2,2,2-trifluoroacetic acid)

Product 1

HCID 141564121(4-nitrophenyl)methyl N-[4-[(2S,4S)-4-[(4-methoxyphenyl)methylsulfanyl]-1-methylpyrrolidine-2-carbonyl]piperazine-1-carboximidoyl]carbamateYield 88.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

480 mg of (2S,4S)-4-(4-methoxybenzylthio)-1-methylpyrrolidine-2-carboxylic acid were suspended in 20 ml of dry acetonitrile, and 325 mg of N,N'-carbonyldiimidazole were added to this suspension, after which the mixture was stirred at 40° C. for 1 hour. At the end of this time, the reaction mixture was cooled with ice, and 980 mg of 1-(4-nitrobenzyloxycarbonylamidino)piperazine bis(trifluoroacetate) [prepared as described in step (a) above] and 320 μl of diisopropylethylamine were added to the mixture, which was then stirred at room temperature overnight. At the end of this time, the reaction mixture was diluted with ethyl acetate and washed with an aqueous solution of sodium hydrogen-carbonate, with water (4 times) and with an aqueous solution of sodium chloride, in that order. The ethyl acetate solution was dried over anhydrous sodium sulfate and then concentrated by evaporation under reduced pressure. The resulting residue was subjected to silica gel column chromatography, eluted with a 4:1 by volume mixture of ethyl acetate and methanol. The fraction containing the desired compound was concentrated by evaporation under reduced pressure, to obtain 860 mg of the title compound, as a powder.

Workup

  1. additionwere added to the mixture, which
  2. stirringwas then stirred at room temperature overnight
  3. washwashed with an aqueous solution of sodium hydrogen-carbonate, with water (4 times) and with an aqueous solution of sodium chloride, in that order
  4. dry with materialThe ethyl acetate solution was dried over anhydrous sodium sulfate
  5. concentrationconcentrated by evaporation under reduced pressure
  6. washeluted with a 4:1 by volume mixture of ethyl acetate and methanol
  7. additionThe fraction containing the desired compound
  8. concentrationwas concentrated by evaporation under reduced pressure

Sources & evidence

ORD record
ord-2f383ebb796841ac84d11be2e68ac621
Source dataset
uspto-grants-1998_01
Patent number
US05712267

Reaction notes

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