HCID 15297072, compound → HCID 178491728, compound

HRID 2289043Notes

Reaction equation

HRID 2289043 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.[N+:27]([C:30]1[CH:65]=[CH:64][C:33]([CH2:34][O:35][C:36]([N:38]=[C:39]([NH:50][C:51]([O:53][CH2:54][C:55]2[CH:60]=[CH:59][C:58]([N+:61]([O-:63])=[O:62])=[CH:57][CH:56]=2)=[O:52])[NH:40][CH2:41][C:42]([NH:44][C@H:45]2[CH2:49][CH2:48][NH:47][CH2:46]2)=[O:43])=[O:37])=[CH:32][CH:31]=1)([O-:29])=[O:28]>C(#N)C.C(N(C(C)C)CC)(C)C.C(OCC)(=O)C>[N+:27]([C:30]1[CH:65]=[CH:64][C:33]([CH2:34][O:35][C:36]([N:38]=[C:39]([NH:50][C:51]([O:53][CH2:54][C:55]2[CH:56]=[CH:57][C:58]([N+:61]([O-:63])=[O:62])=[CH:59][CH:60]=2)=[O:52])[NH:40][CH2:41][C:42]([NH:44][C@H:45]2[CH2:49][CH2:48][N:47]([C:15]([C@@H:11]3[CH2:10][C@H:9]([S:8][CH2:7][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:19][CH:18]=4)[CH2:13][N:12]3[CH3:14])=[O:17])[CH2:46]2)=[O:43])=[O:37])=[CH:32][CH:31]=1)([O-:29])=[O:28]

Participants

6

Reactant 2

HCID 15297072HCID 15297072, compoundHCID 178521336HCID 178521336, compound

Product 1

HCID 178491728HCID 178491728, compoundYield 95.7%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolventHCID 81531DiisopropylethylamineSolvent

Conditions

Temperature
40 °C

Procedure

1.09 g of (2S,4S)-4-(4-methoxybenzylthio)-1-methylpyrrolidine-2-carboxylic acid were suspended in 30 ml of dry acetonitrile, and 691 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 the time, the reaction mixture was cooled with ice, and 2.98 g of (3S)-3-[2-[2,3-bis(4-nitrobenzyloxycarbonyl)guanidino]acetylamino]pyrrolidine trifluoroacetate in 30 ml of dry acetonitrile and 1.7 ml 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 water and brine. 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 10% and 20% methanol-ethyl acetate. The fraction containing the desired compound was concentrated by evaporation under reduced pressure to obtain 2.99 g of (2S,4S)-2-[(3S)-3-[2-[2,3-bis(4-nitrobenzyloxycarbonyl)guanidino]acetylamino]pyrrolidin-1-ylcarbonyl]-4-(4-methoxybenzylthio)-1-methylpyrrolidine, as a powder.

Workup

  1. additionwere added to the mixture, which
  2. stirringwas then stirred at room temperature overnight
  3. washwashed with water and brine
  4. dry with materialThe ethyl acetate solution was dried over anhydrous sodium sulfate
  5. concentrationconcentrated by evaporation under reduced pressure
  6. washeluted with 10% and 20% methanol-ethyl acetate
  7. additionThe fraction containing the desired compound
  8. concentrationwas concentrated by evaporation under reduced pressure

Sources & evidence

ORD record
ord-8d6faadb79ca45019424dd17e1e2c3fe
Source dataset
uspto-grants-2000_07
Patent number
US06090802

Reaction notes

Loading…