تفاعل #969875

ord-eb975f8915e54d90b81363eb67c62aed

معادلة التفاعل

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
المردود 45.0%

المتفاعلات

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

الكواشف

لا شيء

المذيبات

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

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    غسيلwashed with citric acid (10%), NaHCO3 (10%) and brine
  2. 2
    تجفيفThe organic layer was dried (Na2SO4)
  3. 3
    أخرىevaporated to dryness
  4. 4
    أخرىto give F (45% yield)

الإجراء التجريبي

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).

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08236756B2uspto-grants-2012_08