Reacción #969875

ord-eb975f8915e54d90b81363eb67c62aed

Ecuación de reacción

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
Rendimiento 45.0%

Reactantes

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

Reactivos

Ninguno

Disolventes

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

Condiciones de reacción

Condiciones detalladas
See reaction.notes.procedure_details.

Tratamiento posterior

  1. 1
    Lavadowashed with citric acid (10%), NaHCO3 (10%) and brine
  2. 2
    SecadoThe organic layer was dried (Na2SO4)
  3. 3
    Otroevaporated to dryness
  4. 4
    Otroto give F (45% yield)

Procedimiento

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).

Fuente

DOI: 10.6084/m9.figshare.5104873.v1Patente: US08236756B2uspto-grants-2012_08