CH368181A - Process for the preparation of N-aminoalkyl derivatives of azepines - Google Patents
Process for the preparation of N-aminoalkyl derivatives of azepinesInfo
- Publication number
- CH368181A CH368181A CH569562A CH569562A CH368181A CH 368181 A CH368181 A CH 368181A CH 569562 A CH569562 A CH 569562A CH 569562 A CH569562 A CH 569562A CH 368181 A CH368181 A CH 368181A
- Authority
- CH
- Switzerland
- Prior art keywords
- acid
- formula
- iminostilbene
- azepines
- preparation
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title claims description 4
- LCGTWRLJTMHIQZ-UHFFFAOYSA-N 5H-dibenzo[b,f]azepine Chemical compound C1=CC2=CC=CC=C2NC2=CC=CC=C21 LCGTWRLJTMHIQZ-UHFFFAOYSA-N 0.000 claims description 5
- 150000001414 amino alcohols Chemical class 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 4
- 150000004820 halides Chemical class 0.000 claims description 3
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 235000005985 organic acids Nutrition 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 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
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- WNRWEBKEQARBKV-UHFFFAOYSA-N 1-(2-chloroethyl)piperidine Chemical compound ClCCN1CCCCC1 WNRWEBKEQARBKV-UHFFFAOYSA-N 0.000 description 1
- RMGFLMXDCGQKPS-UHFFFAOYSA-N 1-(2-chloroethyl)pyrrolidine Chemical compound ClCCN1CCCC1 RMGFLMXDCGQKPS-UHFFFAOYSA-N 0.000 description 1
- FSNGFFWICFYWQC-UHFFFAOYSA-N 1-(2-chloroethyl)pyrrolidine;hydron;chloride Chemical compound Cl.ClCCN1CCCC1 FSNGFFWICFYWQC-UHFFFAOYSA-N 0.000 description 1
- ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-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
- WXGBMVAPOXRLDB-UHFFFAOYSA-N 6-(2-phenylethenyl)cyclohexa-2,4-dien-1-imine Chemical class N=C1C=CC=CC1C=CC1=CC=CC=C1 WXGBMVAPOXRLDB-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 206010012374 Depressed mood Diseases 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
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-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
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000003868 ammonium compounds Chemical group 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 150000002238 fumaric acids Chemical class 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
- 150000002689 maleic acids Chemical class 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/18—Dibenzazepines; Hydrogenated dibenzazepines
- C07D223/22—Dibenz [b, f] azepines; Hydrogenated dibenz [b, f] azepines
- C07D223/24—Dibenz [b, f] azepines; Hydrogenated dibenz [b, f] azepines with hydrocarbon radicals, substituted by nitrogen atoms, attached to the ring nitrogen atom
- C07D223/26—Dibenz [b, f] azepines; Hydrogenated dibenz [b, f] azepines with hydrocarbon radicals, substituted by nitrogen atoms, attached to the ring nitrogen atom having a double bond between positions 10 and 11
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von N-Aminoalkylderivaten von Azepinen
Im Hauptpatent wird ein Verfahren zur Herstellung von N-Aminoalkylderivaten von Azepinen der Formel I
EMI1.1
X <SEP> X
<tb> <SEP> Alkylen-Am
<tb> worin X Wasserstoff, Halogenatome oder Methyl gruppen, Alkylen einen Alkylenrest mit 2-6 Kohlenstoffato men und 2-4 Brückengliedern zwischen N und Am, und Am einen niedrigmolekularen Dialkylaminorest bedeutet, beschrieben. Dieses Verfahren besteht darin, dass man ein Iminostilben in Gegenwart eines säurebindenden Mittels mit einem reaktionsfähigen Ester eines Aminoalkohols der Formel
HO - Alkylen - Am umsetzt.
Es wurde nun gefunden, dass man Verbindungen der Formel I, worin Am eine Pyrrolidino- oder Piperidinogruppe ist, herstellen kann, wenn man ein Iminostilben der Formel II
EMI1.2
in Gegenwart eines säurebindenden Mittels mit einem reaktionsfähigen Ester eines Aminoalkohols der Formel III
HO-Alkylen-Am III worin Am eine Pyrrolidino- oder Piperidinogruppe bedeutet, umsetzt.
Diese Verbindungen besitzen wertvolle pharmakologischeEigenschaften, insbesondere antiallergische und sedative Wirksamkeit, und kommen unter anderem zur Behandlung von gewissen Formen von Geisteskrankheiten, insbesondere Gemütsdepressionen, in Betracht.
Als säurebindende Mittel eignen sich dabei insbesondere Natriumamid, Lithiumamid, Kaliumamid, Natrium, Lithium oder Kalium. Als reaktionsfähige Ester von Aminoalkoholen der Formel III kommen insbesondere die Halogenide in Frage, wie das Pyrrolidinoäthylchlorid und das Piperidinoäthylchlorid oder die entsprechenden Bromide und Jodide.
Zur Umsetzung geeignete Iminostilbene sind neben dem Iminostilben beispielsweise das 3,7-Dichloriminostilben, 2, 8-Dichlor-iminostilben, 1,9-Dichlor- iminostilben, 3, 7-Dibrom-iminostilben, 3,7-Dimethyl- iminostilben und 2,8 -Dimethyl-iminostilben. Die Ausgangsstoffe erhält man z. B. aus den entsprechenden lminodibenzylverbindungen durch Überführen in leicht spaltbare N-Acylderivate, Halogenierung, z. B. mit Bromsuccinimid, Halogenwasserstoffabspaltung und Hydrolyse, z. B. mittels Ätzalkalien in der Kälte.
Durch Anlagerung von Halogeniden oder Sulfaten aliphatischer oder araliphatischer Alkohole, z. B. von Methyljodid, Dimethylsulfat, Äthylbromid, Äthyl jodid oder Benzylchlorid, kann man aus den tertiären Aminen der Formel I in üblicher Weise monoquaternäre Ammoniumverbindungen erhalten, wobei die Gruppe Am reagiert.
Mit anorganischen oder organischen Säuren, wie Salzsäure, Bromwasserstoffsäure, Schwefelsäure, Phosphorsäure, Methansulfonsäure, Athandisulfon- säure, Essigsäure, Citronensäure, Apfelsäure, Bern steinsäure, Weinsäure, Benzoesäure und Phthalsäure können aus den tertiären Basen Salze gebildet werden, welche zum Teil wasserlöslich sind. Ferner seien Fumar- und Maleinsäure genannt.
Im nachfolgenden Beispiel bedeuten die Teile Gewichtsteile, diese verhalten sich zu Volumteilen wie g zu cm3. Die Temperaturen sind in Celsiusgraden angegeben.
Beispiel
3,86 Teile Iminostilben werden in 50 Volumteilen abs. Benzol gelöst, eine benzolische Lösung der aus 5,4 Teilen ss-Pyrrolidino-äthylchlorid-Hydro- chlorid freigesetzten Base zugefügt und das Ganze auf 60-700 erwärmt. Innerhalb einer halben Stunde lässt man nun eine Suspension von 11 Teilen Natriumamid in Toluol zutropfen und kocht anschlie ssend 18 Stunden unter Rückfluss. Dann kühlt man das Reaktionsgemisch ab und versetzt es mit Wasser.
Die benzolische Schicht wird abgetrennt, zweimal mit Wasser gewaschen und hierauf dreimal mit je 50 Teilen 2-n Essigsäure ausgezogen. Die essigsauren Auszüge werden vereinigt, mit Alkalilauge alkalisch gestellt und ausgeäthert. Der Ätherextrakt wird über Natriumsulfat getrocknet, das Lösungsmittel abdestilliert und der Rückstand im Hochvakuum destilliert.
Das 5-(ss-Pyrrolidino-äthyl)-iminostilben geht unter 0,001 mm Druck bei 172-175 über. Nach Umkristallisation aus Pentan schmilzt es bei 74-74,5".
Das mittels alkoholischer Salzsäure hergestellte Hydrochlorid schmilzt bei 195-196".
In analoger Weise erhält man unter Verwendung der aus 7 Teilen ss, ss-Dimethyl-y-pyrrolidino-propyl- chlorid-Hydrochlorid freigesetzten Base das 5-(fl, ss- Dimethyl- - pyrrolidino - propyl) - iminostilben vom Apo02 169".
Process for the preparation of N-aminoalkyl derivatives of azepines
The main patent describes a process for the preparation of N-aminoalkyl derivatives of azepines of the formula I
EMI1.1
X <SEP> X
<tb> <SEP> Alkylen-Am
<tb> where X is hydrogen, halogen atoms or methyl groups, alkylene is an alkylene radical with 2-6 carbon atoms and 2-4 bridge members between N and Am, and Am is a low molecular weight dialkylamino radical. This method consists in mixing an iminostilbene in the presence of an acid binding agent with a reactive ester of an amino alcohol of the formula
HO - alkylene - Am converts.
It has now been found that compounds of the formula I in which Am is a pyrrolidino or piperidino group can be prepared if an iminostilbene of the formula II
EMI1.2
in the presence of an acid-binding agent with a reactive ester of an amino alcohol of the formula III
HO-Alkylen-Am III in which Am is a pyrrolidino or piperidino group.
These compounds have valuable pharmacological properties, in particular antiallergic and sedative activity, and can be used, inter alia, for the treatment of certain forms of mental illness, in particular mood depression.
Sodium amide, lithium amide, potassium amide, sodium, lithium or potassium are particularly suitable as acid-binding agents. Particularly suitable reactive esters of amino alcohols of the formula III are the halides, such as pyrrolidinoethyl chloride and piperidinoethyl chloride or the corresponding bromides and iodides.
In addition to the iminostilbene, suitable iminostilbenes are, for example, 3,7-dichloriminostilbene, 2,8-dichloro-iminostilbene, 1,9-dichloro-iminostilbene, 3, 7-dibromo-iminostilbene, 3,7-dimethyl-iminostilbene and 8-Dimethyl-iminostilbene. The starting materials are obtained z. B. from the corresponding lminodibenzyl compounds by conversion into easily cleavable N-acyl derivatives, halogenation, e.g. B. with bromosuccinimide, elimination of hydrogen halide and hydrolysis, e.g. B. by means of caustic alkalis in the cold.
By addition of halides or sulfates of aliphatic or araliphatic alcohols, e.g. B. of methyl iodide, dimethyl sulfate, ethyl bromide, ethyl iodide or benzyl chloride, monoquaternary ammonium compounds can be obtained from the tertiary amines of the formula I in the usual manner, the group Am reacting.
With inorganic or organic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, ethanedisulfonic acid, acetic acid, citric acid, malic acid, succinic acid, tartaric acid, benzoic acid and phthalic acid, salts can be formed from the tertiary bases, some of which are water-soluble. Fumaric and maleic acids may also be mentioned.
In the following example, the parts mean parts by weight; these relate to parts by volume as g to cm3. The temperatures are given in degrees Celsius.
example
3.86 parts of iminostilbene are abs in 50 parts by volume. Dissolved benzene, added a benzene solution of the base released from 5.4 parts of β-pyrrolidino-ethyl chloride hydrochloride, and the whole was heated to 60-700. A suspension of 11 parts of sodium amide in toluene is then added dropwise over the course of half an hour and the mixture is then refluxed for 18 hours. The reaction mixture is then cooled and water is added.
The benzene layer is separated off, washed twice with water and then extracted three times with 50 parts of 2N acetic acid each time. The acetic acid extracts are combined, made alkaline with alkali and extracted with ether. The ether extract is dried over sodium sulfate, the solvent is distilled off and the residue is distilled in a high vacuum.
The 5- (ss-pyrrolidino-ethyl) -iminostilbene passes under 0.001 mm pressure at 172-175. After recrystallization from pentane, it melts at 74-74.5 ".
The hydrochloride produced by means of alcoholic hydrochloric acid melts at 195-196 ".
In an analogous manner, using the base released from 7 parts of ss, ss-dimethyl-y-pyrrolidino-propyl chloride hydrochloride, 5- (fl, ss-dimethyl- pyrrolidino-propyl) - iminostilbene from Apo02 169 "is obtained.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH569562A CH368181A (en) | 1956-11-13 | 1957-10-29 | Process for the preparation of N-aminoalkyl derivatives of azepines |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH349988T | 1956-11-13 | ||
| CH569562A CH368181A (en) | 1956-11-13 | 1957-10-29 | Process for the preparation of N-aminoalkyl derivatives of azepines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH368181A true CH368181A (en) | 1963-03-31 |
Family
ID=25698218
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH569562A CH368181A (en) | 1956-11-13 | 1957-10-29 | Process for the preparation of N-aminoalkyl derivatives of azepines |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH368181A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010524975A (en) * | 2007-04-20 | 2010-07-22 | アキュセラ インコーポレイテッド | Styrenyl derivative compounds for treating eye diseases and disorders |
-
1957
- 1957-10-29 CH CH569562A patent/CH368181A/en unknown
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010524975A (en) * | 2007-04-20 | 2010-07-22 | アキュセラ インコーポレイテッド | Styrenyl derivative compounds for treating eye diseases and disorders |
| US8420863B2 (en) | 2007-04-20 | 2013-04-16 | Acucela, Inc. | Styrenyl derivative compounds for treating ophthalmic diseases and disorders |
| US8653142B2 (en) | 2007-04-20 | 2014-02-18 | Acucela Inc. | Styrenyl derivative compounds for treating ophthalmic diseases and disorders |
| US9314467B2 (en) | 2007-04-20 | 2016-04-19 | Acucela Inc. | Styrenyl derivative compounds for treating ophthalmic diseases and disorders |
| US9421210B2 (en) | 2007-04-20 | 2016-08-23 | Acucela Inc. | Styrenyl derivative compounds for treating ophthalmic diseases and disorders |
| US10201545B2 (en) | 2007-04-20 | 2019-02-12 | Acucela Inc. | Styrenyl derivative compounds for treating ophthalmic diseases and disorders |
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