Ipidacrine hydrochloride hydrate, Amiridine, NIK-247, Senita

合成路线:By reaction of 2-aminocyclopent-1-ene-1-carbonitrile (I) with cyclohexanone (II) in presence of polyphosphoric acid in benzene followed by treatment with hydrochloric acid in ethanol.

参考文献标题:Pharmaceutical preparation for learning stimulation and memory improvement
文献作者:Lavretskaya,E.F.; Upadysheva,A.V.; Znamenskaya,A.P.; Sukhanova,S.A.; Grigorieva,N.D.; Penke,I.K.; Timofeeva,A.K.(Nauchno-Issledovatelsky Institut)
参考来源:GB 2192129; US 4735953


合成路线:By reaction of 2-aminocyclopent-1-ene-1-carbonitrile (I) with cyclohexanone (II) in presence of polyphosphoric acid in benzene followed by treatment with hydrochloric acid in ethanol.

参考文献标题:NIK-247
文献作者:Graul,A.; Castar,J.; Prous,J.
参考来源:Drugs Fut 1994,19(4),343


合成路线:The monohydroxylated metabolite of NIK-247,(+)-9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinolin-8-ol (VI) has been synthesized as follows:The condensation of cyclohexane-1,3-dione (I) with 2-amino-1-cyclopentene-1-carbonitrile (II) by means of PPE gives 2-(3-oxo-1-cyclohexen-1-yl)-1-cyclopentene-1-carbonitrile (III),which is cyclized by means of BF3.Et2O to yield 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinolin-8-one (IV).The reduction of (IV) with NaBH4 affords the corresponding racemic alcohol (V),which is submitted to optical resolution with (+)-di-p-toluyltartaric acid to give the desired compound (VI).

合成路线:The monohydroxylated metabolite of NIK-247,(+)-9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinolin-1-ol (XII) has been synthesized as follows:The condensation of cyclopentane-1,3-dione (VIII) with 2-amino-1-cyclohexene-1-carbonitrile (VII) by means of PPE gives 2-(3-oxo-1-cyclopenten-1-yl)-1-cyclohexene-1-carbonitrile (IX),which is cyclized by means of BF3.Et2O to yield 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinolin-1-one (X).The reduction of (X) with NaBH4 affords the corresponding racemic alcohol (XI),which is submitted to optical resolution with (+)-di-p-toluyltartaric acid to give the desired compound (XII).

参考文献标题:Synthesis of estimated metabolites of 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinoline monohydrochloride monohydrate (NIK-247).I.Synthesis of mono-hydroxylated metabolites
文献作者:Komatsu,T.; Yano,M.; Inada,H.; Iwamoto,M.; Okada,K.; Suzuki,K.
参考来源:Yakugaku Zasshi 1995,115(12),1016


合成路线:The synthesis of two dihydroxylated metabolites of NIK-247 has been reported:Two diastereomeric isomers 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinoline-1,8-diol (VI) and (VII) have been synthesized as follows.The oxidation of 2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinolin-9-amine (I) with CrO3.H2SO4 gives 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinoline-1,8-dione (II),which is selectively reduced with 1 equivalent of NaBH4 yielding a mixture of the two hydroxyketones (III) and (IV),separated by crystallization.The optical resolution of (III) with (-)-di-p-toluyltartaric acid affords the pre (+)-isomer (V),which is further reduced with NaBH4 to afford a diastereomeric mixture of the 1,8-diols (VI) and (VII),which is separated by HPLC over Chiracel OG in n-hexane ethanol (9:1).
参考文献标题:Synthesis of estimated metabolites of 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinoline monohydrochloride monohydrate (NIK-247).II.Synthesis of dihydroxylated metabolites
文献作者:Komatsu,T.; Yano,M.; Iwamoto,M.; Kobayashi,M.; Suzuki,K.
参考来源:Yakugaku Zasshi 1995,115(12),1022