Patent CA-1150265-A (CA)
Inventor: GUILLAUME JACQUES
IPC: A61K31/44
Filed: 1980-06-11
Granted: 1983-07-19
Abstract: For the Contracting States : BE, CH, LI, DE, FR, GB, IT, LU, NL, SE 1. Compounds with the formula (I) :  see diagramm : EP0021924,P23,F1 in which : - R represents a hydrogen atom, an alkyl radical containing from 1 to 8 carbon atoms or an aralkyl radical containing from 7 to 12 carbon atoms. - X represents a hydrogen atom or an alkyl radical containing from 1 to 8 carbon atoms, - Y represents a hydrogen atom or a halogen atom, - Z represents a hydrogen atom, an alkyl or hydroalkyl radical containing from 1 to 8 carbon atoms, an aryloxyalkyl radical containing from 7 to 12 carbon atoms, an aralkyl radical containing from 7 to 12 carbon atoms possibly substituted by one or more halogen atoms, by one or more alkoxy radicals containing from 1 to 4 carbon atoms, by one or more alkyl radicals containing from 1 to 4 carbon atoms, or by one or more radicals OH, CF3 , OCF3 , NO2  or NH2 or Z represents a cycloalkyl-alkyl radical containing from 4 to 12 carbon atoms, an alkenyl radical containing from 3 to 8 carbon atoms or an alkynyl radical containing from 3 to 8 carbon atoms and, - either a and b each represent a hydrogen atom, - or a represents a hydrogen atom and b represents a hydroxyl radical or an alkoxy radical containing from 1 to 8 carbon atoms, - or a and b together form a double carbon-carbon bond as well as the salts of addition with acids of the compounds with the formula (I). For the Contracting State : AT 1. Process for the preparation of compounds with the formula (I) :  see diagramm : EP0021924,P25,F1  in which : - R represents a hydrogen atom, an alkyl radical containing from 1 to 8 carbon atoms or an aralkyl radical containing from 7 to 12 carbon atoms, - X represents a hydrogen atom or an alkyl radical containing from 1 to 8 carbon atoms, - Y represents a hydrogen atom or a halogen atom, - Z represents a hydrogen atom, an alkyl or hydroalkyl radical containing from 1 to 8 carbon atoms, an aryloxyalkyl radical containing from 7 to 12 carbon atoms, an aralkyl radical containing from 7 to 12 carbon atoms possibly substituted by one or more halogen atoms, by one or more alkoxy radicals containing from 1 to 4 carbon atoms, by one or more alkyl radicals containing from 1 to 4 carbon atoms, or by one or more radicals OH, CF3 , OCF3 , NO2  or NH2 or Z represents a cycloalkyl-alkyl radical containing from 4 to 12 carbon atoms, an alkenyl radical containing from 3 to 8 carbon atoms or an alkynyl radical containing from 3 to 8 carbon atoms and, - either a and b each represent a hydrogen atom, - or a represents a hydrogen atom and b represents a hydroxyl radical or an alkoxy radical containing from 1 to 8 carbon atoms, - or a and b together form a double carbon-carbon bond as well as the salts of addition with acids characterized in that a compound with the formula (I).  see diagramm : EP0021924,P25,F2  in which X represents a hydrogen atom or an alkyl radical containing from 1 to 8 carbon atoms and Hal represents a halogen atom is submitted to the action of an alkylation or aralkylation agent, so as to obtain a compound with the formula (III) :  see diagramm : EP0021924,P25,F3  in which R' represents an alkyl radical containing from 1 to 8 carbon atoms or an aralkyl radical containing from 7 to 12 carbon atoms, which is converted into an organo-magnesium derivative, so as to obtain a compound with the formula (IV) :  see diagramm : EP0021924,P25,F4  which is condensed with N-benzyl 3-piperidone, so as to obtain a compound with the formula (IA ) :  see diagramm : EP0021924,P26,F5  then, if desired - either the compound with the formula (IA ) is submitted to the action of a dehydratation agent, so as to obtain a compound with the formula (IB ) :  see diagramm : EP0021924,P26,F6  which if desired, in the case where R' represents a benzyl radical is submitted to the action of a selective cleavage agent for the benzyl group carried by the nucleus of the indole, so as to obtain a compound with formula (IC ) :  see diagramm : EP0021924,P26,F7  which, if desired, is submitted to the action of a cleavage agent for the benzyl group carried by the tetrahydropyridinyl nucleus, so as to obtain the compound of the formula (ID ) :  see diagramm : EP0021924,P26,F8  - or the compound with the formula (IA ) is submitted to the action of a cleavage agent for the benzyl group carried by the nitrogen of the piperidinyl group, so as to obtain a compound with the formula (IE ) :  see diagramm : EP0021924,P26,F9  which if desired is submitted to the action of a dehydratation agent, so as to obtain a compound with the formula (IF ) :  see diagramm : EP0021924,P26,F10  - or, in the case where R' represents a benzyl group the compound with the formula (IA ) is submitted to the action of a selective cleavage agent for the benzyl group carried by the indole nucleus, so as to obtain a compound with the formula (IG ) :  see diagramm : EP0021924,P26,F11 which, if desired, is submitted to the action of a cleavage agent for the benzyl group carried by the piperidinyl nucleus so as to obtain a compound with the formula (IH ) :  see diagramm : EP0021924,P26,F12 then, if desired, each of the compounds obtained which respond to the formula (I) in which Z represents a hydrogen atom is submitted to the action of an agent able to introduce a radical Z', Z' having the same significante as Z, set out in claim 1, with the exception of hydrogen, so as to obtain the corresponding compounds with the formula (I) in which the nitrogen atom of the piperidinyl nucleus carries a radical Z' and, if desired, - either each of the compounds obtained responding to the formula (I) in which b represents a hydroxyl radical is submitted to the action of an etherification agent, so as to obtain the corresponding compounds with the formula (I) in which b represents an alkoxy radical containing from 1 to 8 carbon atoms, - or each of the compounds obtained responding to the formula (I) in which b represents a hydroxyl radical is submitted to the action of a dehydratation agent, so as to obtain the corresponding compounds with the formula (I) in which a and b together form a double carbon-carbon bond, - or each of the compounds obtained responding to the formula (I) in which b represents a hydroxyl radical, is submitted to the action of a cleavage agent for the hydroxyl group, so as to obtain the corresponding compounds with the formula (I) in which a and b each represent a hydrogen atom and, if desired each of the compounds with the formula (I) so obtained is submitted to the action of a halogenation agent able to introduce a halogen atom Hal in position 3 of the indole, so as to obtain the corresponding compound with the formula (I) in which Y represents a halogen atom, and if desired, each of the compounds with the formula (I) previously obtained is submitted to the action of an acid so as to form its salt.