Method of manufacturing of 7-ethyl-10-[4-(1-piperidino)-1- piperidino]- carbonyloxy- camptothecin

1. A method of preparation of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-camptothecin of formula I

wherein 7-ethyl-10-hydroxycamptothecin of formula II

is subjected to a condensation reaction with 1-chlorocarbonyl-4-piperidinopiperidine hydrochloride of formula III

in a polar aprotic solvent in the presence of 4-dimethylaminopyridine.

2. The method according to claim 1 , wherein 1-chlorocarbonyl-4-piperidinopiperidine hydrochloride is employed in an amount of 1.3 to 3 mol, per 1 mol of 7-ethyl-10-hydroxycamptothecin.

3. The method according to claim 1 , wherein 4-dimethylaminopyridine is employed in an amount of 1.5 to 4 mol, per 1 mol of 7-ethyl-10-hydroxycamptothecin.

4. The method according to claim 1 , wherein the polar aprotic solvent is employed in an amount of 400 to 600 mol, per 1 mol of 7-ethyl-10-hydroxycamptothecin.

5. The method according to claim 1 , wherein the condensation reaction is carried out at a temperature of 70 to 80° C.

6. The method according to claim 1 , wherein the polar aprotic solvent is acetronitrile.

7. The method according to claim 2 , wherein 1-chlorocarbonyl-4-piperidinopiperidine hydrochloride is employed in an amount of 1.6 to 1.9 mol of 7-ethyl-10-hydroxycamptothecin.

8. the method according to claim 1 , wherein 4-dimethylaminopyridine is employed in an amount of 1.8 to 2.2 per 1 mol of 7-ethyl-10-hydroxycamptothecin.

9. The method according to claim 1 , wherein the polar aprotic solvent is employed in an amount of 430 to 460 mol of 7-ethyl-10-hydroxycamptothecin.

10. The method according to claim 1 , wherein the condensation reactin is carried out at a temperature of 73 to 77° C.