Reaktion #969875

ord-eb975f8915e54d90b81363eb67c62aed

Reaktionsgleichung

Cl
HCl
CCN(C(C)C)C(C)C
diisopropylethylamine
CC(C)[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)N1CCC[C@H]1C(=O)O
Fmoc-Val-Pro-OH
COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1
doxorubicin
→
CC(C)[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)N1CCC[C@H]1C(=O)O.COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1
Fmoc-Val-Pro doxorubicin
Ausbeute 45.0%

Edukte

Cl
HCl
CCN(C(C)C)C(C)C
diisopropylethylamine
—
N-[(dimethylamino)1H-1,2,3-triazolo[4,5-b]pyridino-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide
CC(C)[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)N1CCC[C@H]1C(=O)O
Fmoc-Val-Pro-OH
COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1
doxorubicin

Reagenzien

Keine

Lösungsmittel

CS(C)=O
DMSO
CCOC(C)=O
ethyl acetate

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    Waschenwashed with citric acid (10%), NaHCO3 (10%) and brine
  2. 2
    TrocknenThe organic layer was dried (Na2SO4)
  3. 3
    Sonstigeevaporated to dryness
  4. 4
    Sonstigeto give F (45% yield)

Vorschrift

A solution of Fmoc-Val-Pro-OH and doxorubicin. HCl (50 mg, 0.08 mmol) in DMSO (4 mL), was successively treated at room temperature with N-[(dimethylamino)1H-1,2,3-triazolo[4,5-b]pyridino-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide (HATU) (36.0 mg, 0.09 mmol) and diisopropylethylamine (DIEA) (29.5 μL, 0.17 mmol). The reaction mixture was stirred at room temperature overnight. Then, the solvent was lyophilized and the residue was dissolved in ethyl acetate and washed with citric acid (10%), NaHCO3 (10%) and brine. The organic layer was dried (Na2SO4) and evaporated to dryness to give F (45% yield).

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08236756B2uspto-grants-2012_08