Reaktion #1997587

Reaktionsgleichung

acetic acid

6-(Methacryloylamino)hexanoylhydrazine

doxorubicin

HCl

→

6-(Methacryloylamino)hexanoylhydrazine Doxorubicin

Lösungsmittel

methanol chloroform acetic acid

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe reaction mixture stirred at room temperature for 24 hours
2. 2
   workup.STIRRINGwas stirred at room temperature for another 4 hours
3. 3
   SonstigeThe product was purified from polymeric and low-molecular impurities by means of gel chromatography in a column (30 cm×3 cm)
4. 4
   workup.ADDITIONfilled with Sephadex
5. 5
   EinengenThe filtrate was concentrated to 2 ml
6. 6
   Sonstigethe product precipitated into 30 ml of diethyl ether
7. 7
   Waschenwashed with a small amount of diethyl ether, and vacuum
8. 8
   Sonstigedried to constant weight

Vorschrift

6-(Methacryloylamino)hexanoylhydrazine (40 mg, 0.188 mmol) was dissolved in 6 ml of methanol at room temperature. The solution was poured into a reaction vessel in which doxorubicin.HCl (115 mg, 0.198 mmol) was placed and the suspension was stirred vigorously. 310 μl of acetic acid was added to the suspension and the reaction mixture stirred at room temperature for 24 hours. The reaction process was monitored by TLC-Silicagel 60 F254 plates (methanol:chloroform:acetic acid 2:8:1, Rf(DOX)=0.75, Rf(MA-AH-NHN=DOX)=0.9). 100 mg of copolymer 1 was then added to the homogenous reaction mixture (to bind the residual free DOX) and the reaction mixture was stirred at room temperature for another 4 hours. The product was purified from polymeric and low-molecular impurities by means of gel chromatography in a column (30 cm×3 cm) filled with Sephadex LH-20 in methanol. The filtrate was concentrated to 2 ml and the product precipitated into 30 ml of diethyl ether. The product was sucked off, washed with a small amount of diethyl ether, and vacuum dried to constant weight. The yield was 110 mg of product (79%) with the melting point of 172 to 175° C. TLC (methanol:chloroform:acetic acid 2:8:1): one stain at Rf=0.9. MALDI-TOF MS: 762 (M+Na).

Quelle