| 主权项 |
1. A process for the preparation of a compound of formula (I):in which:
R1 and R2 are, independently of one another, selected from the group consisting of a hydrogen atom and a methyl radical; R3 and A together form a C3-C8 saturated aliphatic ring, comprising one or more heteroatomsor
R3 represents a radical chosen from the group consisting of a hydrogen atom, a C1-C4 alkyl radical and a benzyl radical and A represents a radical chosen from the group consisting of a hydrogen atom, a C1-C4 alkyl radical, a benzyl radical and a group of formula (II):in which
a varies from 2 to 5, R4 and B together form a C3-C8 ring or R4 represents a radical chosen from the group consisting of a hydrogen atom, a C1-C4 alkyl radical and a benzyl radical, it being possible for R3 and R4 to be connected by an alkylene chain comprising 2 or 3 carbon atoms, and B represents a radical chosen from the group consisting of:
a hydrogen atom,a C1-C4 alkyl radical,a benzyl radical,a group of formula (III): in which b varies from 2 to 5, c varies from 2 to 5 and R5 to R7 represent, independently of one another, a radical chosen from the group consisting of a hydrogen atom, a C1-C4 alkyl radical and a benzyl radical, it being possible for R4 and R5 and/or R5 and R6 and/or R6 and R7 to be connected by an alkylene chain comprising 2 or 3 carbon atoms, anda group of formula (IV): in which c varies from 2 to 5 and R8 and R9 represent, each independently of one another, a hydrogen atom or a C1-C5 alkyl radical, it being possible for R4 and R8 to be connected by an alkylene chain comprising 2 or 3 carbon atoms, or R8 and R9 together form a C3-C8 ring,or a pharmaceutically acceptable salt thereof,comprising the following successive stages:
a) starting from podophyllotoxin of formula (VIII): b) if appropriate, preparation by demethylation of a compound of formula (V): in which R1 and R2 are as defined above, then c) reaction of the compound of formula (V) or (VIII) with chloroacetonitrile in an acidic medium and then, if appropriate, demethylation reaction, to provide a compound of formula (VI): in which R1 and R2 are as defined above; then d) reaction of the compound of formula (VI) with a compound of formula (VII): in which R3 and A are as defined above, the amines optionally present in the group A being protected by an appropriate protective group, in a mixture of solvents comprising a polar aprotic solvent, in the presence of a Lewis base. |
