反应 #969875

ord-eb975f8915e54d90b81363eb67c62aed

反应方程式

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
收率 45.0%

反应物

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

试剂

无

溶剂

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

反应条件

详细条件
See reaction.notes.procedure_details.

后处理

  1. 1
    洗涤washed with citric acid (10%), NaHCO3 (10%) and brine
  2. 2
    干燥The organic layer was dried (Na2SO4)
  3. 3
    其他evaporated to dryness
  4. 4
    其他to give F (45% yield)

实验过程

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).

来源

DOI: 10.6084/m9.figshare.5104873.v1专利: US08236756B2uspto-grants-2012_08