GB800969A - Novel 2-hydroxy-benzo [ª‡] quinolizines, acid addition salts thereof and a process for the manufacture of same - Google Patents
Novel 2-hydroxy-benzo [ª‡] quinolizines, acid addition salts thereof and a process for the manufacture of sameInfo
- Publication number
- GB800969A GB800969A GB3722/57A GB372257A GB800969A GB 800969 A GB800969 A GB 800969A GB 3722/57 A GB3722/57 A GB 3722/57A GB 372257 A GB372257 A GB 372257A GB 800969 A GB800969 A GB 800969A
- Authority
- GB
- United Kingdom
- Prior art keywords
- hydroxy
- benzo
- dimethoxy
- quinolizine
- hexahydro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/04—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing a quinolizine ring system condensed with only one six-membered carbocyclic ring, e.g. julolidine
- C07D455/06—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing a quinolizine ring system condensed with only one six-membered carbocyclic ring, e.g. julolidine containing benzo [a] quinolizine ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
This invention comprises compounds of the general formula: <FORM:0800969/IV (b)/1> and acid addition salts thereof, wherein R1 and R2 each represent a hydrogen atom or a hydroxy or alkoxy group or together represent an alkylenedioxy group, and R3 represents an alkyl group, an alkyl group which contains an oxygen atom in the form of a normal or cyclic ether function, or an alkenyl or aralkyl group, and wherein the broken lines denote that the isocyclic ring may contain one or two further double bonds; and a process for the manufacture thereof by reducing a compound of the general formula: <FORM:0800969/IV (b)/2> and, if desired, converting the product into an acid addition salt. Reduction may be effected by hydrogen in the presence of a hydrogenation catalyst, in which case alkenyl groups are also reduced to alkyl groups, by alkali metal in the presence of an alcohol, or by the use of lithium-aluminium hydride or sodium boron hydride. In an example, 2-oxo-3 - ethyl - 9,10 - dimethoxy - 1,2,3,4,6,7 - hexahydro - benzo - [a] - quinolizine is hydrogenated in glacial acetic acid, in the presence of prehydrogenated platinum oxide catalyst at ca. 20 DEG C. to form 2-hydroxy-3-ethyl-9,10-dimethoxy - 1,2,3,4,6,7 - hexahydro - benzo -[a] - quinolizine. The same compound is also prepared in further examples from the same starting material by hydrogenation in methanol, in the presence of Raney-nickel, with hydrogen under pressure at 50 DEG C.; by reaction with metallic sodium in butanol; and by reaction with lithium-aluminium hydride in the presence of a mixture of dioxane and ether (1 : 4), followed by hydrolysis with water. In each case, the hydrobromide, the hydrochloride and the acid sulphate are formed. 2-Hydroxy-3-n-butyl-9,10 - dimethoxy - 1,2,3,4,6,7 - hexahydrobenzo-[a]-quinolizine is prepared from the corresponding 2-oxo-compound by hydrogenation in methanol and in glacial acetic acid, by reduction with metallic sodium and butanol and by reduction with lithium-aluminium hydride, the base being converted into the hydrobromide; and 2,9,10 - trihydroxy - 3 - ethyl - 1,2,3,4,6,7-hexahydrohydro - benzo - [a] - quinolizine hydrobromide is prepared from its corresponding 2-oxo-compound, in the form of its hydrobromide, by hydrogenation in 50 per cent acetic acid in the presence of a platinum oxide catalyst. (The product is identical with that obtained by hydrolysis of the 2-hydroxy-3-ethyl - 9,10 - dimethoxy - 1,2,3,4,6,7 - hexahydro - benzo - [a] - quinolizine, formed above, with 48 per cent hydrobromic acid.) The following may also be prepared by the methods given: 2-hydroxy-3-methyl-, 2-hydroxy-3-isobutyl-, 2-hydroxy-3-amyl-, 2-hydroxy-3-hexyl-, and 2 - hydroxy - 3 - (o - methoxy - butyl) - 9,10-dimethoxy - 1,2,3,4,6,7 - hexahydro - benzo - [a] - quinolizines and their hydrochlorides; 2-hydroxy - 3 - allyl -, and 2 - hydroxy - 3 - (tetrahydro - furfuryl) - 9,10 - dimethoxy - 1,2,3,4,6,7 - hexahydro - benzo - [a] - quinolizines and their hydrobromides; 2-hydroxy-3-ethyl - 9,10 - diethoxy and 2 - hydroxy - 3 - ethyl - 9,10 - methylenedioxy - 1,2,3,4,6,7 - hexahydro-benzo-[a]-quinolizines and their hydrochlorides, 2,9,10 - trihydroxy - 3 - butyl - 1,2,3,4,6,7 - hexahydro - benzo - [a] - quinolizine and its hydrobromide; 2-hydroxy-3-benzyl - 9,10 - dimethoxy - 1,2,3,4,6,7 - hexahydro - benzo - [a] - quinolizine and its picrate; and 2-hydroxy-3-ethyl- and 2-hydroxy-3-butyl-1,2,3,4,6,7,8,9,10,11 - decahydrobenzo - [a] - quinolizines. Starting materials: 2-Oxo-3-ethyl-9,10-dimethoxy - 1,2,3,4,6,7 - hexahydro - benzo - [a]-quinolizine is prepared by reacting 1-ethoxycarbonylmethyl - 6,7 - dimethoxy - 1,2,3,4 - tetrahydro - isoquinoline, paraformaldehyde and dimethyl monoethyl-malonate to form 1-ethoxycarbonylmethyl - 2 - [21,21 - di - (methoxycarbonyl) - butyl] - 6,7 - dimethoxy - 1,2,3,4 - tetrahydro-isoquinoline which is then reacted with sodium ethoxide to effect ring closure, and then with 3-n-hydrochloric acid to effect hydrolysis and decarboxylation. The product is isolated as the base which is converted into the hydrochloride and hydrobromide. 2-Oxo-3-ethyl - 9,10 - dihydroxy - 1,2,3,4,6,7 - hexahydrobenzo-[a]-quinolizine hydrobromide is prepared from the corresponding 9,10-dimethoxy compound or its hydrobromide by hydrolysis with 48 per cent hydrobromic acid. Specification 789,789 is referred to.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH341161T | 1956-02-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB800969A true GB800969A (en) | 1958-09-03 |
Family
ID=4505675
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB3722/57A Expired GB800969A (en) | 1956-02-08 | 1957-02-04 | Novel 2-hydroxy-benzo [ª‡] quinolizines, acid addition salts thereof and a process for the manufacture of same |
Country Status (8)
| Country | Link |
|---|---|
| AT (1) | AT196875B (en) |
| BE (1) | BE554816A (en) |
| CH (1) | CH341161A (en) |
| DE (1) | DE1082912B (en) |
| DK (1) | DK89401C (en) |
| ES (1) | ES233470A1 (en) |
| FR (1) | FR1231641A (en) |
| GB (1) | GB800969A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010026436A2 (en) * | 2008-09-08 | 2010-03-11 | Biovail Laboratories International (Barbados) Srl | Pharmaceutical compounds |
| WO2011019956A2 (en) | 2009-08-12 | 2011-02-17 | Biovail Laboratories International (Barbados) S.R.L. | Pharmaceutical compositions |
| WO2018178243A3 (en) * | 2017-04-01 | 2018-12-13 | Adeptio Pharmaceuticals Limited | Dihydrotetrabenazine for use in the treatment a movement disorder |
| US10660885B2 (en) | 2017-04-01 | 2020-05-26 | Adeptio Pharmaceuticals Limited | Pharmaceutical compositions |
| US10668052B2 (en) | 2017-04-01 | 2020-06-02 | Adeptio Pharmaceuticals Limited | Combinations of isomers of dihydrotetrabenazine |
| US11065232B2 (en) | 2017-04-01 | 2021-07-20 | Adeptio Pharmaceuticals Limited | Dihydrotetrabenazine for the treatment of anxiety and psychoses |
| US11844786B2 (en) | 2017-04-01 | 2023-12-19 | Adeptio Pharmaceuticals Limited | Uses of combinations (+)-α-dihydrotetrabenazine and (−)-α-dihydrotetrabenazine in methods of treating movement disorder |
| US12042493B2 (en) | 2018-05-23 | 2024-07-23 | Adeptio Pharmaceuticals Limited | Pharmaceutical compounds for use in treating Huntington's disease |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU175890B (en) * | 1977-06-15 | 1980-11-28 | Chinoin Gyogyszer Es Vegyeszet | Process for producing new 1,2,3,4,6,7-hexahydro-11-b-alpha-benzo-square bracket-a-square brecket closed-quinolyzine derivatives |
-
1956
- 1956-02-08 CH CH341161D patent/CH341161A/en unknown
-
1957
- 1957-01-31 DE DEH29179A patent/DE1082912B/en active Pending
- 1957-01-31 AT AT196875D patent/AT196875B/en active
- 1957-02-04 GB GB3722/57A patent/GB800969A/en not_active Expired
- 1957-02-06 FR FR731133A patent/FR1231641A/en not_active Expired
- 1957-02-07 BE BE554816A patent/BE554816A/en unknown
- 1957-02-07 ES ES0233470A patent/ES233470A1/en not_active Expired
- 1957-02-08 DK DK47057A patent/DK89401C/en active
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010026436A2 (en) * | 2008-09-08 | 2010-03-11 | Biovail Laboratories International (Barbados) Srl | Pharmaceutical compounds |
| WO2010026436A3 (en) * | 2008-09-08 | 2010-06-24 | Biovail Laboratories International (Barbados) Srl | 1,3, 4, 6, 7, 11b-hexahydro-benzo[alpha]quinolizines for the treatment of hyperkinetic movement and related disorders |
| WO2011019956A2 (en) | 2009-08-12 | 2011-02-17 | Biovail Laboratories International (Barbados) S.R.L. | Pharmaceutical compositions |
| WO2018178243A3 (en) * | 2017-04-01 | 2018-12-13 | Adeptio Pharmaceuticals Limited | Dihydrotetrabenazine for use in the treatment a movement disorder |
| US10660885B2 (en) | 2017-04-01 | 2020-05-26 | Adeptio Pharmaceuticals Limited | Pharmaceutical compositions |
| US10668052B2 (en) | 2017-04-01 | 2020-06-02 | Adeptio Pharmaceuticals Limited | Combinations of isomers of dihydrotetrabenazine |
| US11065232B2 (en) | 2017-04-01 | 2021-07-20 | Adeptio Pharmaceuticals Limited | Dihydrotetrabenazine for the treatment of anxiety and psychoses |
| US11103498B2 (en) | 2017-04-01 | 2021-08-31 | Adeptio Pharmaceuticals Limited | Pharmaceutical compositions |
| RU2768738C2 (en) * | 2017-04-01 | 2022-03-24 | Адептио Фармасьютикалз Лимитед | USE OF (−)-α-DIHYDROTETRABENAZINE OR A COMBINATION THEREOF WITH (+)-α-DIHYDROTETRABENAZINE IN THE TREATMENT OF HYPERKINETIC MOVEMENT DISORDER, AS WELL AS CORRESPONDING METHODS |
| US11844794B2 (en) | 2017-04-01 | 2023-12-19 | Adeptio Pharmaceuticals Limited | Pharmaceutical compositions |
| US11844786B2 (en) | 2017-04-01 | 2023-12-19 | Adeptio Pharmaceuticals Limited | Uses of combinations (+)-α-dihydrotetrabenazine and (−)-α-dihydrotetrabenazine in methods of treating movement disorder |
| US12042493B2 (en) | 2018-05-23 | 2024-07-23 | Adeptio Pharmaceuticals Limited | Pharmaceutical compounds for use in treating Huntington's disease |
Also Published As
| Publication number | Publication date |
|---|---|
| ES233470A1 (en) | 1957-10-16 |
| BE554816A (en) | 1960-02-12 |
| AT196875B (en) | 1958-03-25 |
| DK89401C (en) | 1960-07-25 |
| DE1082912B (en) | 1960-06-09 |
| CH341161A (en) | 1959-09-30 |
| FR1231641A (en) | 1960-09-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HU193161B (en) | Process for preparing new n-alkyl-norscopines | |
| GB800969A (en) | Novel 2-hydroxy-benzo [ª‡] quinolizines, acid addition salts thereof and a process for the manufacture of same | |
| US2599001A (en) | Nu, nu-disubstituted-beta-haloalkylamines | |
| GB1492757A (en) | Process for the manufacture of polyaddition products containing imide groups | |
| US2655498A (en) | N-benzhydbyl-n alkyl-substituted | |
| GB977224A (en) | Amine compounds | |
| US3449418A (en) | Etherified bisaryl compounds | |
| IL42384A (en) | N-benzhydryl-n'-p-hydroxybenzyl-piperazines and processes for their manufacture and pharmaceutical compositions containing them | |
| GB763434A (en) | Manufacture of alkanolamines | |
| US3112311A (en) | 2-phenyl-5, 6-dimethyl-morpholines and 2-phenyl-5, 6-tetramethylene-morpholines | |
| GB758382A (en) | Improvements in bis-(ú-aminophenoxy) alkane derivatives | |
| GB1456799A (en) | Preparation of 1-methylpiperazine and 1,4-dimethylpiperazine as co-products | |
| GB773780A (en) | Improvements in or relating to the preparation of substituted morpholines | |
| GB685750A (en) | Improvements in or relating to isoquinoline derivatives | |
| GB1062626A (en) | Synthesis of í¸s,14-bisdehydrooestrone 3-ethers and intermediates therefor | |
| US3855237A (en) | Process of making hexahydro-1h-furo(3,4-c) pyrrole | |
| GB930676A (en) | Process for the preparation of 20-alkylamino steroid derivatives and novel 20-alkylamino steroid derivatives prepared thereby | |
| GB971752A (en) | Phenyl-alkylamines,their manufacture and use | |
| US3287460A (en) | Hydrogenation process for the preparation of piperidyl-(4)-ethers | |
| DE1966053C3 (en) | Oxazoltdone (4) derivatives | |
| US3111514A (en) | Aminoalkylbiguanides | |
| ES442709A1 (en) | A procedure for preparing new piperazine derivatives. (Machine-translation by Google Translate, not legally binding) | |
| KR880009955A (en) | Piperazine Derivatives and Methods for Making the Same | |
| ES356456A2 (en) | Process for the Manufacture of Amine Derivatives | |
| GB785389A (en) | Aralkyl carbinols and process for their preparation |