Thiophene-containing potentially neuroleptic rigid spiroamines. II. Synthesis of some N,N-dimethylamino-substituted spiro[H-cyclohepta[2,1-b;4,5-b]dithiophene-9,1'-cycloalkanes
Gronowitz, S.; Svensson, L.; Stjernström, N.; Ogren, S.O.
Acta Pharmaceutica Suecica 16(6): 365-375
1979
ISSN/ISBN: 0001-6675 PMID: 44635 Document Number: 144011
A new synthetic route to potentially neuroleptic rigid spiro amines has been worked out. The key new step consists of the reaction of the 2-lithium derivative, derived from 1,2-di-(3-thienyl)ethanes, such as 5-chloro-2-lithio-3-[2-(2'-methyl-4'-thienyl)ethyl]thiophene with 1,4-dioxaspiro[4,5]decan-8-one, followed by electrophilic ring-closure of the intermediate carbinol, such as 8-[5-chloro-3-(2-(2'-methyl-4'-thienyl)ethyl)-2-thienyl]-1,4-dioxaspiro[4,5]decan-8-ol to the spiro compound 2-chloro-4,5-dihydro-7-methylspiro-[9H-cyclohepta[2,1-b; 4,5-b']dithiophene-9,1'-cyclohexan]-4'-one, which by conventional methods could be transformed in 2 steps to 2-chloro-4,5-dihydro-N,N,7-trimethylspiro[9H-cyclohepta[2,1-b; 4,5-b']dithiophene-9,1'-[2]cyclohexen]-4'-amine. 2-Chloro-4,5-dihydro-N,N,7-trimethylspiro[9H-cyclohepta[2,1-b; 4,5-b']dithiophene-9,1'-[2]-cyclohexen]-4'-amine, 2-chloro-4,5-dihydro-N,N-dimethylspiro[9H-cyclohepta[2,1-b; 4,5-b']dithiophene-9,1'-cyclohexan]-4'-amine and 2-chloro-4,5-dihydro-N,N,7-trimethylspiro[9H-cyclohepta[2,1-b; 4,5-b']dithiophene-9,1'-cyclohexan]4'-amine], which were also prepared, had no ability to inhibit apomorphine-induced stereotypies in the rat.