CH484928A - Process for the preparation of basic substituted heterocycles - Google Patents
Process for the preparation of basic substituted heterocyclesInfo
- Publication number
- CH484928A CH484928A CH1817069A CH1817069A CH484928A CH 484928 A CH484928 A CH 484928A CH 1817069 A CH1817069 A CH 1817069A CH 1817069 A CH1817069 A CH 1817069A CH 484928 A CH484928 A CH 484928A
- Authority
- CH
- Switzerland
- Prior art keywords
- sep
- formula
- preparation
- addition salts
- acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 title description 3
- 239000002253 acid Substances 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 claims description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims 1
- NPUACKRELIJTFM-UHFFFAOYSA-N cr gas Chemical class C1=NC2=CC=CC=C2OC2=CC=CC=C21 NPUACKRELIJTFM-UHFFFAOYSA-N 0.000 claims 1
- 125000000565 sulfonamide group Chemical group 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 125000004434 sulfur atom Chemical group 0.000 claims 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- ICBZSKCTKKUQSY-YUWZRIFDSA-N 4-[(1r,2s)-1-hydroxy-2-(methylamino)propyl]phenol;hydrochloride Chemical compound Cl.CN[C@@H](C)[C@H](O)C1=CC=C(O)C=C1 ICBZSKCTKKUQSY-YUWZRIFDSA-N 0.000 description 1
- -1 4-ethyl-1-piperazinyl Chemical group 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 229940125683 antiemetic agent Drugs 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung basisch substituierter Heterocyclen Die Erfindung betrifft ein Verfahren zur Herstellung von eine Sulfonamidcyruppe enthaltenden 11-basisch substütuierten
EMI0001.0005
sowie von Säure-Additionssalzen davon. In Formel I stellt Z ein Sauerstoff atom, ein Schwe#felatorn oder eine Iminogruppe (-NH-) dar.
R, ist niedriges Alkyl, niedriges Hydroxyalkyl, welches acyliert sein kann, oder Alkoxyalkyl nüt höch-
EMI0001.0017
Dibenz[b.f1-1,4-oxazepinen, Diben#zo[b,f]-1,4-thiazepinen und Dibenzo[b,e]-1,4-diazepinen der Formel: stens <B>5</B> C-Atomen. Unter niedrigem Alkyl usw. wird solches mit<B>1</B> bis<B>3</B> C-Atomen verstanden.
Die gewünschten Produkte werden erhalten, wenn man eine Verbindung der Formel: worin Z die obengenannte Bedeutung hat, mit einem reaktionsfähigen Ester eines Alkohols der Formel RI-OH, worin R, die obengenannte Bedeutung hat, umsetzt.
Als reaktionsfähige Ester von Alkoholen der For mel Rj-OH kommen insbesondere Halogenwasserstoff- säurcester in Betracht, Die Umsetzung er-folgt.vorzugs- weise in einem inerten Lösungsmittel, z. B. Benzol oder Aceton, durch Erwärmen auf Rückflusstemperatur.
Die in der beschriebenen Weise erhaltenen Basen sind in den meisten Fällen kristallisierbar, sonst im Hochvakuum unzersetzt destillierbar, und bilden mit anorganischen und organischen Säuren, beispielsweise Salzsäure, Bromwasserstoffsäure, Schwefelsäure, Sal petersäure, Phosphorsäure, Essigsäure, Oxalsäure, Wein säure, Toluolsulfc>nsäure und dergleichen, in Wasser be ständige Additionssalze, in welcher Form die Produkte ebenfalls verwendet werden können.
Die in der beschriebenen Weise erhaltenen Basen und ihre Säureadditionssalze sind neue Verbindungen, die als Wirkstoffe in Arzneimitieln Verwendung finden. Sie üben eine günstige Wirkung auf das Zentralnerven- systern aus und fallen als Neuroleptika, Sedativa und insbesondere als Antiemetika in Betracht.
<I>Beispiel<B>1</B></I> 5,4<B>g</B> 2-Dimethylarrünosulfonyl-11-(#l-piperazinyl)- dibenz[b,f]-1,4-oxazepin werden in<B>50</B> ml Aceton gelöst, mit<B>1 g</B> wasserfreiem Kaliumcarbonat. und 2,24<B>g</B> Äthyljodid in 20 nil Aceton versetzt und während <B>3</B> Stunden unter Rühren auf Rückfluss erhitzt. Anschlie ssend wird das Reaktionsgemisch im Vakuum einge dampft. Der Rückstand wird zwischen verdünnter Natronlauge und Äther verteilt, und die Ätherauszüge werden mit Wasser gewaschen und nüt verdünnter Salz säure erschöpfend ausgeschüttelt.
Die sauren Auszüge werden mit konzentrierter NatronIauge alkalisch gestellt und mit Chloroform ausgeschütielt. Die Chloroform- auszüge werden mit Wasser gewaschen, mit Natrium sulfat getrocknet und im Vakuum zur Trockne einge dampft. Der Rückstand wird aus Aceton/Petroläther kristaffisiert, wobei man 4,9<B>g</B> 2-Dimethviaminosulfonyl- 11-(4-äthyl-l-piperazinyl)-dibenz[b,f]-1.,4-oxazepin vom Schmelzpunkt 160-161'C erhält.
Bei analogem Vorgehen wie in dem vorerwähnten Beispiel erhält man weiterhin die in der nachfolgenden Tabelle erwähnten Produkte entsprechend Formel<B>1.</B> In der Tabelle haben Z und R, die frühei genannte Bedeutung. > In de er Kolonne rechts bedeuuet Ac Aceton, Ae Äther,
Ch Chloroform und Pe Petroläther.
EMI0002.0054
<I>Tabelle</I>
<tb> Beispiel <SEP> <B>-Z-</B> <SEP> R, <SEP> Physikalische <SEP> Konstanten
<tb> 2 <SEP> <B>-s- <SEP> -CH3</B> <SEP> B & cp-: <SEP> Smp. <SEP> <B>192-193'C</B> <SEP> (aus <SEP> Ac/Pe)
<tb> <B>3 <SEP> -0-</B> <SEP> -CHs <SEP> Base: <SEP> Smp. <SEP> 149-150'C <SEP> (aus <SEP> Ae/Pe)
<tb> <I>4</I> <SEP> <B>-NH- <SEP> -CH3</B> <SEP> Base: <SEP> Smp. <SEP> <B>193-195'C</B> <SEP> (aus <SEP> Ac/Pe)
<tb> <B><I>5</I> <SEP> -0- <SEP> -CH2---#e--OH</B> <SEP> Base: <SEP> Smp. <SEP> <B>164-166' <SEP> C</B> <SEP> (aus <SEP> Ac/Ae/Pe)
Process for the Production of Basically Substituted Heterocycles The invention relates to a process for the production of 11-base substituted heterocycles containing a sulfonamido group
EMI0001.0005
as well as acid addition salts thereof. In formula I, Z represents an oxygen atom, a sulfurator or an imino group (-NH-).
R, is lower alkyl, lower hydroxyalkyl, which can be acylated, or alkoxyalkyl at most
EMI0001.0017
Dibenz [b.f1-1,4-oxazepines, Diben # zo [b, f] -1,4-thiazepines and dibenzo [b, e] -1,4-diazepines of the formula: at least <B> 5 </ B > C atoms. Lower alkyl, etc., is understood to mean that with 1 to 3 carbon atoms.
The desired products are obtained when a compound of the formula: in which Z has the abovementioned meaning, is reacted with a reactive ester of an alcohol of the formula RI-OH, in which R, has the abovementioned meaning.
Particularly suitable reactive esters of alcohols of the formula Rj-OH are hydrohalic acid esters. The reaction is preferably carried out in an inert solvent, e.g. B. benzene or acetone, by heating to reflux temperature.
The bases obtained in the manner described are in most cases crystallizable, otherwise they can be distilled without decomposition in a high vacuum, and form with inorganic and organic acids, for example hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, acetic acid, oxalic acid, tartaric acid, toluenesulfonic acid and the like, permanent addition salts in water, in which form the products can also be used.
The bases obtained in the manner described and their acid addition salts are new compounds which are used as active ingredients in medicaments. They have a beneficial effect on the central nervous system and can be used as neuroleptics, sedatives and, in particular, as antiemetics.
<I>Example<B>1</B> </I> 5.4 <B> g </B> 2-Dimethylarrünosulfonyl-11 - (# l-piperazinyl) - dibenz [b, f] -1.4 -oxazepine are dissolved in <B> 50 </B> ml acetone with <B> 1 g </B> anhydrous potassium carbonate. and 2.24 g of ethyl iodide in 20 nil acetone are added and the mixture is heated to reflux for 3 hours while stirring. The reaction mixture is then evaporated in vacuo. The residue is distributed between dilute sodium hydroxide solution and ether, and the ether extracts are washed with water and exhaustively shaken out using dilute hydrochloric acid.
The acidic extracts are made alkaline with concentrated sodium hydroxide solution and extracted with chloroform. The chloroform extracts are washed with water, dried with sodium sulfate and evaporated to dryness in vacuo. The residue is crystallized from acetone / petroleum ether, 4.9 g of 2-dimethviaminosulfonyl-11- (4-ethyl-1-piperazinyl) -dibenz [b, f] -1., 4- oxazepine with a melting point of 160-161 ° C.
If the procedure is analogous to that in the above-mentioned example, the products mentioned in the table below corresponding to formula 1. In the table, Z and R have the meaning given earlier. > In the column on the right, acetone means acetone, Ae ether,
Ch chloroform and Pe petroleum ether.
EMI0002.0054
<I> table </I>
<tb> Example <SEP> <B> -Z- </B> <SEP> R, <SEP> physical <SEP> constants
<tb> 2 <SEP> <B> -s- <SEP> -CH3 </B> <SEP> B & cp-: <SEP> Smp. <SEP> <B> 192-193'C </B> <SEP> (from <SEP> Ac / Pe)
<tb> <B> 3 <SEP> -0- </B> <SEP> -CHs <SEP> Base: <SEP> Smp. <SEP> 149-150'C <SEP> (from <SEP> Ae / Pe)
<tb> <I> 4 </I> <SEP> <B> -NH- <SEP> -CH3 </B> <SEP> Base: <SEP> Smp. <SEP> <B> 193-195'C </B> <SEP> (from <SEP> Ac / Pe)
<tb> <B> <I> 5 </I> <SEP> -0- <SEP> -CH2 --- # e - OH </B> <SEP> Base: <SEP> Smp. <SEP> <B> 164-166 '<SEP> C </B> <SEP> (from <SEP> Ac / Ae / Pe)
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1817069A CH484928A (en) | 1967-05-09 | 1967-05-09 | Process for the preparation of basic substituted heterocycles |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH655767A CH484924A (en) | 1967-05-09 | 1967-05-09 | Process for the preparation of basic substituted heterocycles |
| CH1817069A CH484928A (en) | 1967-05-09 | 1967-05-09 | Process for the preparation of basic substituted heterocycles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH484928A true CH484928A (en) | 1970-01-31 |
Family
ID=25699780
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1817069A CH484928A (en) | 1967-05-09 | 1967-05-09 | Process for the preparation of basic substituted heterocycles |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH484928A (en) |
-
1967
- 1967-05-09 CH CH1817069A patent/CH484928A/en not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |