Patent GB-1409073-A (GB)
Title: 8-substituted dibenzobicyclo-3,2,1 octadienes
IPC: C07C67/00
Filed: 1972-10-27
Abstract: 1409073 8-Aminoalkyl dibenzobicyclo[3.2.1]- octadienes RIKER LABORATORIES Inc 27 Oct 1972 [29 Oct 1971] 49741/72 Heading C2C The novel compounds of Formula A wherein R<SP>1</SP> is H or C 1 -C 4  alkyl ,R 2  is C 1 -C 4 - alkyl and -alkis -CH 2 -; -CH 2 -CH 2 - or in both syn- and anti-isomeric forms and acid addition salts thereof may be prepared by reaction of 8 - hydroxyalkyl - dibenzobicyclo- [3.2.1]octadiene to replace the hydroxyl group of this compound with a primary or secondary amine residue of Formula B 8 - Carbozydibenzobicyclo[3.2.1]octadiene is prepared by reacting the 8-chlorocompund with magnesium and treating the resulting Grignard compound with carbon dioxide. 8 - (N - methyl - and 8 - N,N - dimethylcarboxamido)dibenzobicyclo[3.2.1]octadiene are prepared by treating the 8-carboxylic acid with thionyl chloride and then with methylamine or dimethylamine respectively. Syn - 8 - hydroxymethyldibenzobicyclo[3.2.1]- octadiene is prepared from the 8-carboxylic acid by treatment with (CH 3 OCH 2 CH 2 O) 2 NaAlH 4 . Anti - 8 - (2 - hydroxyethyl) dibenzobicyclo - [3.2.1]octadiene is prepared by reaction of the 8-Grignard reagent (above) with ethylene oxide. Anti - 8 - (thydroxyethyl)dibenzobicyclo[3.2.1]- octadiene is prepared by reaction of the 8- Grignard regent (above) with acetaldehyde. 8 - Methylsulphonyloxyalkyl derivatives of the above hydroxy compounds are prepared by reaction with methane sulphonylchloride in the presence of a base, e.g. triethylamine or pyridine. Syn - 8 - (cyanomethyl)dibenzobicyclo[3.2.1]- octadiene is prepared by reaction of the corresponding 8-(methylsulphonyl oxymethyl) compound with potassium cyanide. Anti - 8 - (N - acetyl) - N - methylanimomethyldibenzobicyclo[3.2.1]octadiene is prepared by reaction of the corresponding 8-N-methylaminomethyl compound with acetic anhydride and is reduced to 8-(N-ethyl-N-methylaminomethyl)dibenzobicyclo [3.2.1]octadiene. 8 - (N - methyl and N,N - dimethylanimomethyl)dibenzobicyclo[3.2.1]octadiene are prepared by reduction of corresponding the 8- amides with borane. Syn - 8 - (2 - animoethyl)dibenzobicyclo[3.2.1]- octadiene is prepared by reduction of the corresponding 8-cyanomethyl compound with borane and is reacted with formaldehyde and formic acid to obtain syn-8-[(2-N,N-dimethylamino)- ethyl]dibenzobiyclo[3.2.1]octadiene. Anti - 8 - [2 - (N,N - dimethylamino)ethyl]dibenzobicyclo[3.2.1]octadiene is prepared by reacting the corresponding 8-(2-methanesulphonoxyethyl) compound (above) with dimethyl amine. Anti - 8 - [1 - (N,N - dimethylamino)ethyl]- dibenzobicyclo[3.2.1]octadiene is prepared by reacting the corresponding 8-2-hydroxyethylcompound with dimethylamine. In the above, where no isomer is specified, both syn and anti isomers are obtained by similar methods from the appropriate starting material. Pharmaceutical compositions having central nervous system activity, particularly antidepressant activity, for oral or parenteral administration comprise a compound of Formula I or acid addition salt thereof together with known organic or inorganic inert pharmaceutical carrier materials.