Ammonia → (S)-3-[(2S,3R,4R,5S)-5-(N-benzyloxycarbonyl-L-leucyl)amino-2,3,4,6-tetrahydroxyhexanoyl]amino-3-phenylpropionamide

HRID 2230407Notes

Reaction equation

HRID 2230407 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:17]([NH:19][C@@H:20]([CH2:41][OH:42])[C@@H:21]([OH:40])[C@@H:22]([OH:39])[C@H:23]([OH:38])[C:24]([NH:26][C@H:27]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:28][C:29](O)=[O:30])=[O:25])=[O:18])[CH2:13][CH:14]([CH3:16])[CH3:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O[N:44]1C(=O)CCC1=O.C1(N=C=NC2CCCCC2)CCCCC1.N>C(#N)C.CN(C)C=O>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:17]([NH:19][C@@H:20]([CH2:41][OH:42])[C@@H:21]([OH:40])[C@@H:22]([OH:39])[C@H:23]([OH:38])[C:24]([NH:26][C@H:27]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:28][C:29]([NH2:44])=[O:30])=[O:25])=[O:18])[CH2:13][CH:14]([CH3:15])[CH3:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 10868DicyclohexylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 59902690(S)-3-[(2S,3R,4R,5S)-5-(N-benzyloxycarbonyl-L-leucyl)amino-2,3,4,6-tetrahydroxyhexanoyl]amino-3-phenylpropionic acid

Product 1

HCID 59902676(S)-3-[(2S,3R,4R,5S)-5-(N-benzyloxycarbonyl-L-leucyl)amino-2,3,4,6-tetrahydroxyhexanoyl]amino-3-phenylpropionamideYield 32.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of (S)-3-[(2S,3R,4R,5S)-5-(N-benzyloxycarbonyl-L-leucyl)amino-2,3,4,6-tetrahydroxyhexanoyl]amino-3-phenylpropionic acid (295 mg), N-hydroxysuccinimide (58 mg) and N,N′-dicyclohexylcarbodimide (103 mg) in acetonitrile (10 ml) was stirred at room temperature for 3 hours and the formed insoluble solid was filtrated off. Removal of the organic solvent gave a residue, which was dissolved in dimethylformamide (5 ml), followed by addition of 25% aqueous ammonia solution (1 ml). The mixture was stirred at room temperature for 1 hour and concentrated under reduced pressure. The residue was extracted with ethyl acetate and the extract was washed with 1N hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine respectively. After drying over anhydrous sodium sulfate, removal of the organic solvent gave a residue, which was recrystallized from methanol-diethylether to give the title compound (97 mg).

Workup

  1. filtrationthe formed insoluble solid was filtrated off
  2. customRemoval of the organic solvent
  3. customgave a residue, which
  4. concentrationconcentrated under reduced pressure
  5. extractionThe residue was extracted with ethyl acetate
  6. washthe extract was washed with 1N hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine respectively
  7. dry with materialAfter drying over anhydrous sodium sulfate, removal of the organic solvent
  8. customgave a residue, which
  9. customwas recrystallized from methanol-diethylether

Sources & evidence

ORD record
ord-b9cb9809e1664d61bb75cd5375bec9bc
Source dataset
uspto-grants-2002_07
Patent number
US06423869B1

Reaction notes

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