Patent ID: 6500953
Filing Date: 2002-12-31
Classification: C07D

Abstract:
Process for preparing derivatives of nothapodytine or derivatives of mappicine or of camptothecin, whereina) 4-ethyl-2-methylhepta-2,4-dienoic acid is reacted on a 3-aminomethyl-2-bromoquinoline derivative of general formula: â€ƒin which R1 and R2 may be hydrogen atoms or R1 represents a halogen atom or an alkyl radical, R2 is a radical having the structure â€”Oâ€”COâ€”X as defined above for the derivatives of camptothecin or R1 and R2 are as defined for the known derivatives of camptothecin or represent radicals which are protected or which can be easily converted to the radicals R1 and R2 cited above, to give the quinoline derivative of general formula: â€ƒin which R1 and R2 are as defined above; b) to the quinoline derivative obtained, (2-methoxycarbonylvinyl)tributyltin is added in the presence of a complex of palladium and triphenylarsine, to give the quinoline derivative of general formula: â€ƒin which R1 and R2 are as defined above; c) the quinoline derivative obtained is cyclized to give the tetracyclic derivative of general formula: â€ƒin which R1 and R2 are as defined above, then this derivative is subjected to ozonolysis followed by treatment with dimethyl sulfide to give the ketone derived from the tetracyclic compound of general formula: â€ƒin which R1 and R2 are as defined above; d) the tetracyclic derivative thus obtained is saponified and then decarboxylated under oxidizing conditions to give the nothapodytine derivative of general formula: â€ƒin which R1 and R2 are as defined above, and then the derivative obtained is optionally converted to a camptothecin derivative or to a mappicine derivative.