1,8-Diazabicyclo(5.4.0)undec-7-ene → (R)-2-((S)-2-amino-3-(1H-indol-3-yl)propanamido)-3-(tert-butyldisulfanyl)propanoic acid

HRID 1482287Notes

Reaction equation

HRID 1482287 reaction equation
C1C2C(COC([NH:18][C@@H:19]([CH2:34][C:35]3[C:43]4[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=4)[NH:37][CH:36]=3)[C:20]([NH:22][C@@H:23]([CH2:27][S:28][S:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:24]([OH:26])=[O:25])=[O:21])=O)C3C(=CC=CC=3)C=2C=CC=1.C1CCN2C(=NCCC2)CC1>CN(C)C=O>[NH2:18][C@@H:19]([CH2:34][C:35]1[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[NH:37][CH:36]=1)[C:20]([NH:22][C@@H:23]([CH2:27][S:28][S:29][C:30]([CH3:32])([CH3:31])[CH3:33])[C:24]([OH:26])=[O:25])=[O:21]

Participants

4

Reactant 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 117735889(R)-2-((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(1H-indol-3-yl)propanamido)-3-(tert-butyldisulfanyl)propanoic acid

Product 1

HCID 89668660(R)-2-((S)-2-amino-3-(1H-indol-3-yl)propanamido)-3-(tert-butyldisulfanyl)propanoic acidYield 91%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of the prepared (R)-2-((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(1H-indol-3-yl)propanamido)-3-(tert-butyldisulfanyl)propanoic acid (Fmoc-Trp-Cys(StBu)-OH) (Compound SP602) (500 mg, 0.809 mmol) in N,N-dimethylformamide (1.6 mL) was mixed with 1,8-diazabicyclo[5.4.0]-7-undecene (DBU) (134 μL, 0.890 mmol) with stirring at room temperature, and the reaction solution was stirred at room temperature for 30 minutes. The reaction solution was purified by reverse-phase silica gel column chromatography (0.1% aqueous formic acid solution/0.1% formic acid-acetonitrile solution) to afford (R)-2-((S)-2-amino-3-(1H-indol-3-yl)propanamido)-3-(tert-butyldisulfanyl)propanoic acid (H-Trp-Cys(StBu)-OH) (Compound SP639) (290 mg, 0.733 mmol, 91%).

Workup

  1. stirringthe reaction solution was stirred at room temperature for 30 minutes
  2. customThe reaction solution was purified by reverse-phase silica gel column chromatography (0.1% aqueous formic acid solution/0.1% formic acid-acetonitrile solution)

Sources & evidence

ORD record
ord-27b23a914b4c46a9a08768f7f67422eb
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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