US 4,267,330 A · Process for the synthesis of vincadifformine and related derivatives

Abstract

This invention relates to the preparation of vincadifformine and related derivatives which are useful as starting material for the synthesis of vincamine and other related compounds possessing interesting psychopharmacologic properties. A N-benzyl-tetrahydro-.gamma.-carboline compound (III) is halogenated with t-butyl hypochlorite to obtain a haloindolenine compound which is directly treated with a metal dialkyl malonate such as thallium dialkyl malonate to provide a dialkyl 3-benzyl-1,2,3,4,5,6-hexahydroazepino (4,5-b) indole-5,5-dicarboxylate compound, said latter compound being hydrogenated to provide a dialkyl 1,2,3,4,5,6 hexahydroazepino (4,5-b) indole-5,5-dicarboxylate, said latter compound being condensed with a functionalized aldehyde, typically a haloaldehyde, to provide vincadifformine or a related derivative by passing through an intermediate compound being a salt of a dialkyl 3,3-(alkenyl)-1,2,3,4,5,6-hexahydroazepino(4,5-b) indolinium-(5,5)-dicarboxylate.

Claims29

Dependent claims

A process for the preparation of vincadifformine or related compound of the formula I ##STR12## wherein each R.sub.1 and R.sub.2 individually is hydrogen, or hydroxy, or carbamate, or lower alkoxy, or lower alkyl having from one to 7 carbon atoms, or halo, or a combination of such substituents;

R.sub.3 and R.sub.4 are the same or different and are hydrogen or alkyl having from one to 7 carbon atoms;
A represents an alkyl chain or from 2 to 5 carbon atoms and which may be substituted by at least one alkyl, hydroxy, or hydroxy-alkyl groups of from 1 to 7 carbon atoms, characterised in condensing a dialkyl 1,2,3,4,5,6-hexahydroazepino (4,5-b) indole-5,5-dicarboxylate of the formula VI ##STR13## wherein R.sub.1, R.sub.2 and R.sub.4 are as defined above, and R'.sub.4 is as defined for R.sub.4 ;
with a straight chain or branched chain aldehyde selected from the group of halo aldehyde, arylsulfoxy aldehyde, lower alkylsulfoxy aldehyde or epoxy aldehyde and having from three to fourteen carbon atoms to produce vincadifformine or a related compound of the formula I.

A process for the preparation of vincadifformine or related compound of the formula I ##STR14## wherein each R.sub.1 and R.sub.2 individually is hydrogen, or hydroxy, or carbamate, or lower alkoxy, or lower alkyl having from one to 7 carbon atoms, or halo, or a combination of such substituents;

R.sub.3 and R.sub.4 are the same or different and are hydrogen or alkyl having from one to 7 carbon atoms;
A represents an alkyl chain from 2 to 5 carbon atoms and which may be substituted by at least one alkyl, hydroxy, or hydroxy-alkyl groups of from 1 to 7 carbon atoms, characterised in condensing a dialkyl 1,2,3,4,5,6-hexahydroazepino(4,5-b)indole-5,5-dicarboxylate of the formula VI ##STR15## wherein R.sub.1, R.sub.2, and R.sub.4 are as defined above, and R'.sub.4 is as defined for R.sub.4 ;
with a straight chain or branched chain aldehyde selected from the group of halo aldehyde, arylsulfoxy aldehyde, lower alkoxysulfoxy aldehyde or epoxy aldehyde and having from three to fourteen carbon atoms to produce vincadifformine or a related compound of the formula I;
and which further includes reacting a N-benzyltetrahydro-.gamma.-carboline of the formula III ##STR16## wherein R.sub.1 and R.sub.2 are as defined above and .phi. means phenyl with t-butyl hypochlorite to obtain a halogenoindolenine;
directly treating said halogenoindolenine with a sodium dialkyl malonate or thallium dialkyl malonate to thereby provide a dialkyl 3-benzyl-1,2,3,4,5,6-hexahydroazepino(4,5-b)indole-5,5-dicarboxylate of the formula V:
##STR17## hydrogenating the compound of formula V in the presence of a palladium on charcoal hydrogenation catalyst to provide the dialkyl 1,2,3,4,5,6-hexahydroazepino(4,5-b)indole-5,5-dicarboxylate (VI).

3 more elements

Dependencies are inferred from the claim text.

Process for the synthesis of vincadifformine and related derivatives

Life of this patent

Process for the synthesis of vincadifformine and related derivatives

Life of this patent

Abstract

Claims29