Réaction #969875

ord-eb975f8915e54d90b81363eb67c62aed

Équation de réaction

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
Rendement 45.0%

Réactifs

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

Réactifs

Aucun

Solvants

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

Conditions de réaction

Conditions détaillées
See reaction.notes.procedure_details.

Traitement

  1. 1
    Lavagewashed with citric acid (10%), NaHCO3 (10%) and brine
  2. 2
    SéchageThe organic layer was dried (Na2SO4)
  3. 3
    Autreevaporated to dryness
  4. 4
    Autreto give F (45% yield)

Mode opératoire

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).

Source

DOI: 10.6084/m9.figshare.5104873.v1Brevet: US08236756B2uspto-grants-2012_08