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Lawesson's reagent → methyl (2S)-4-[bis(2-{[(tert-butoxy)carbonyl]amino}ethyl)carbamothioyl]-2-{[(tert-butoxy) carbonyl]amino}butanoate

HRID 1923973
Notes
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Reaction equation

HRID 1923973 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][N:11]([CH2:29][CH2:30][NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:12]([CH2:14][CH2:15][C@H:16]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:17]([O:19][CH3:20])=[O:18])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:48])=CC=1>C1COCC1.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][N:11]([CH2:29][CH2:30][NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:12]([CH2:14][CH2:15][C@H:16]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:17]([O:19][CH3:20])=[O:18])=[S:48])=[O:7])([CH3:4])([CH3:3])[CH3:2]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 87949Lawesson's reagent2×HCID 59366631Methyl N2-(tert-butoxycarbonyl)-N5,N5-bis(2-((tert-butoxycarbonyl)amino)ethyl)-L-glutaminate

Product 1

HCID 59366732methyl (2S)-4-[bis(2-{[(tert-butoxy)carbonyl]amino}ethyl)carbamothioyl]-2-{[(tert-butoxy) carbonyl]amino}butanoateYield 45.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridine
Catalyst
HCID 8028TetrahydrofuranSolvent

Procedure

To the solution of methyl (2S)-4-[bis(2-{[(tert-butoxy)carbonyl]amino}ethyl)carbamoyl]-2-{[(tert-butoxy)carbonyl]amino}butanoate XIV (610 mg, 1.12 mmol) in THF (10 mL) under argon was added Lawesson's reagent (680 mg, 1.68 mmol) and DMAP (13 mg, 0.11 mmol). The mixture was stirred at r.t. for 2 h and then refluxed over weekend. An additional two portions of Lawesson's reagent (900 mg, 2.24 mmol) and was added and the reaction was refluxed for another 4 h. The solvent was evaporated under reduced pressure and the crude product was purified on a silica gel column (1:6 EtOAc/hexane) to give methyl (2S)-4-[bis(2-{[(tert-butoxy)carbonyl]amino}ethyl)carbamothioyl]-2-{[(tert-butoxy)carbonyl]amino}butanoate XV (290 mg, 0.51 mmol, 45% yield). ESIMS found for C25H46N4O8S m/z 563 (M+H).

Workup

  1. temperaturerefluxed over weekend
  2. temperaturethe reaction was refluxed for another 4 h
  3. customThe solvent was evaporated under reduced pressure
  4. customthe crude product was purified on a silica gel column (1:6 EtOAc/hexane)

Sources & evidence

ORD record
ord-958c97d2ade64a5fb392cb6788a138eb
Source dataset
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08178490B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes