DE1545956A1 - Process for the preparation of benzodiazepine derivatives - Google Patents
Process for the preparation of benzodiazepine derivativesInfo
- Publication number
- DE1545956A1 DE1545956A1 DE19631545956 DE1545956A DE1545956A1 DE 1545956 A1 DE1545956 A1 DE 1545956A1 DE 19631545956 DE19631545956 DE 19631545956 DE 1545956 A DE1545956 A DE 1545956A DE 1545956 A1 DE1545956 A1 DE 1545956A1
- Authority
- DE
- Germany
- Prior art keywords
- acid
- hydrogen
- alkyl
- preparation
- alkanol
- 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.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/20—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
- C07D243/26—Preparation from compounds already containing the benzodiazepine skeleton
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Inductance-Capacitance Distribution Constants And Capacitance-Resistance Oscillators (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Description
HAN 4008/33-002HAN 4008 / 33-002
7» Hoffmann-la Roche St Qo. Aktiengesellschaft. Basel (Schweiz) 7 “Hoffmann-la Roche St Qo. Corporation . Basel, Switzerland)
O CD OO ■Ρ»O CD OO ■ Ρ »
Die Erfindung betrifft ein Verfahren zur Herstellung von Benzodiazepin-Derivaten der allgemeinen FormelThe invention relates to a process for the preparation of benzodiazepine derivatives of the general formula
(D(D
worin R, Wasserstoff, Alkanoyl oder Aralkanoyl, R2 Wasserstoff oder Alkyl, R, Alkyl, R4 Wasserstoff, Halogen oder Trifluormethyl und R5 Wasserstoff, Halogen, Trifluormethyl, Nitro, Alkylthic oder Alkyl bedeuten,where R, hydrogen, alkanoyl or aralkanoyl, R 2 is hydrogen or alkyl, R, alkyl, R 4 is hydrogen, halogen or trifluoromethyl and R 5 is hydrogen, halogen, trifluoromethyl, nitro, alkylthic or alkyl,
und deren Säureadditionssalze.and their acid addition salts.
kettige und verzweigte niedere Alkyl- bzw. Alkenylgruppen, wie Methyl, Aethyl, Propyl, Isopropyl, Allyl und dergleichen. Der Ausdruck Alkanoyl betrifft geradkettige und verzweigt· niedere alipathisohe Carbonaäuregruppen, wie Acetyl, Fro-chain and branched lower alkyl or alkenyl groups, such as methyl, ethyl, propyl, isopropyl, allyl and the like. The term alkanoyl relates to straight-chain and branched lower aliphatic carboxylic acid groups, such as acetyl, free
eADeAD
-2.- 15A5956-2.- 15A5956
pionyl,Butyryl, Ieovaleroyl und dergleichen.pionyl, butyryl, leovaleroyl, and the like.
Sas erfindungsgemässe Verfahren ist dadurch gekennzeichnet , dass man eine Verbindung der allgemeinen Formel The inventive method is characterized in that a compound of the general formula
(II)(II)
worin R, , R2, R- und R1- die vorstehend angegebene Bedeutung haben und Rg Wasserstoff, Alkanoyl, Aroyl oder Aralkanoyl bedeutet,wherein R ,, R 2 , R- and R 1 - have the meaning given above and Rg is hydrogen, alkanoyl, aroyl or aralkanoyl,
mit einem Alkanol umsetzt und erwünsentenfalls die erhaltene Verbindung in ein Salz überführt.Reacts with an alkanol and, if necessary, the obtained Compound converted into a salt.
Das erfindungsgemässe Verfahren wird zweckmassigerweise durch Behandlung eines Säureadditionssalzes, z.B. eines Hydrohalogenides, wie des Hydrochlorides, einer VerbindungThe method according to the invention is expediently by treating an acid addition salt, e.g., a hydrohalide such as the hydrochloride, of a compound
ο der Formel II mit einem Alkanol durchgeführt. Manο of the formula II carried out with an alkanol. Man
^ kann diese Verbindung der Formel II auch in Form der^ this compound of formula II can also be used in the form of
--. Base oder in Form eines Säureadditonssalzes mit einem AiH a--. Base or in the form of an acid addition salt with an AiH a-
""* in Anwesenheit einer Säure, wie einer Halogenwaseerstot* . ·"" * in the presence of an acid such as a halogen water stot *. ·
z.B. Chlorwasserstoffsäure, umsetzen. Die Reaktion mit einem Alkanol kann zweckmässigerweise unter Verwendung des in der Reaktion verwendeten Alkanols als Lösungsmittel oder in A-for example hydrochloric acid. The reaction with an alkanol can conveniently using the alkanol used in the reaction as a solvent or in A-
BAD ORIGINALBATH ORIGINAL
Wesenheit eineB inerten organischen Lösungsmittelsdurchgeführt werden. Die Behandlung kann ausserdem in Anwesenheit oder Abwesenheit von Wasser erfolgen. Die Umsetzung kann bei Raumtemperatur oder zweckmässigerweiee bei erhöhten Temperaturen vorgenommen werfen. VbrtAiIMfterweis· arbeitet man bei der Rückflusstemperi/fcur des Alkanols, z.B. im Falle von niedermolekularen Alkanolen, zwischen etwa 60 und 80°·An inert organic solvent will. The treatment can also take place in the presence or absence of water. The reaction can be carried out at room temperature or expediently at elevated temperatures. VbrtAiIMfterweis · one works at the reflux temperature of the alkanol, e.g. in the case of low molecular weight alkanols, between about 60 and 80 °
Die im erfindungsgemässen Verfahren verwendeten Ausgangsmaterialien der Formel II, worin R6 Alkanoyl, Aroyl oder Alkanoyl ist, können durch Umsetzung einer Verbindung der allgemeinen FormelThe starting materials of the formula II used in the process according to the invention, in which R 6 is alkanoyl, aroyl or alkanoyl, can be prepared by reacting a compound of the general formula
(III)(III)
worin R,, Rp, R. und R^ die vorstehende Bedeutung haben,wherein R ,, Rp, R. and R ^ the above Have meaning
mit einem Säureanhydrid, Diacyleulfld oder Säurehalogenid (die Chloride Bind be-with an acid anhydride, diacyl sulphide or acid halide (the chlorides B ind
. werden f bi/. will n f bi /
. werden f wobei^ voreugt) gewonneriYeine Abspaltung dee Sauerstoff atome in 4- . let n f with ^ in advance) a splitting off of the oxygen atoms in 4-
sbewirkt wirdj^
stoffatoms in 3-StellungY^DTe3BReaktion wird zweckmäesiger weise in einem üblichen organischen lösungsmittel, wie Dime
thylformamid , Pyridin oder dergleichen, durchgeführt. Bei s is effected j ^
Substance atom in the 3-position Y ^ DTe3B reaction is expediently carried out in a common organic solvent such as dimethylformamide , pyridine or the like. at
BAD ORIGINALBATH ORIGINAL
Verwendung eines Säureanhydride oder eine Diacylsulfid als Aoylierungsmittel gönnen diese Säureanhydride oder Diacylsulfide auoh direkt ale Reaktionsmedium dienen. Sie Umsetzung kann bei Raumtemperatur oder auoh oberhalb oder unterhalb der Raumtemperatur durchgeführt werden.Using an acid anhydride or a diacyl sulfide as an aoylating agent, these acid anhydrides or diacyl sulfides also serve directly as a reaction medium. You implementation can be carried out at room temperature or above or below room temperature.
Falls R. in Formel III Wasserstoff ist, erhält man Verbindungen der Formel H» worin R1 und Rg dieselben Acylgruppen sind. Anderseits kann man bei Verwendung eines Ausgangsmaterials der Formel III, worin R1 bereite eine Acylgruppe bedeutet, Verbindungen erhalten, worin R. unverändert ist und dementsprechend B~ und Rg dieselben oder verschiedene Acylgruppen bedeuten. Bs wurde ausserdem festgestellt, dass bei Verwendung von . Dimethylformamid als Reaktionsmedium Verbindungen der Formel III, worin R1 Wasserstoff ist, selektiv unter Bildung von Verbindungen der Formel I, worin R1 Wasserstoff ist, aoyliert werden können. Bs wurde ausserdem festgestellt, dass die Aroylierung selektiv an der 3-Steilung erfolgt und das Stickstoffatom in 2-Steilung nicht beeinflusst.If R. in formula III is hydrogen, compounds of the formula H »in which R 1 and Rg are the same acyl groups are obtained. On the other hand, when using a starting material of the formula III, in which R 1 is already an acyl group, compounds can be obtained in which R. is unchanged and, accordingly, B ~ and Rg mean the same or different acyl groups. Bs was also found that when using. Dimethylformamide as the reaction medium Compounds of the formula III in which R 1 is hydrogen can be selectively aoylated to form compounds of the formula I in which R 1 is hydrogen. It was also found that the aroylation takes place selectively at the 3-position and does not affect the nitrogen atom in the 2-position.
Verbindungen der Formel II, worin R, Alkanoyl, Aroyl oder Aralkanoyl ist, können zu entsprechenden Verbindungen, worin Rg Wasserstoff ist, hydrolysiert weiden. Man kann einej /alkalische Hydrolyse oder eine saure Hydrolyse vornehmen.Compounds of the formula II in which R is alkanoyl, aroyl or aralkanoyl can be hydrolyzed to corresponding compounds in which Rg is hydrogen. An alkaline hydrolysis or an acid hydrolysis can be carried out.
Die letztere wird vorzugsweise durch Behandlung des Ausgangsmaterials mit einer wässrigen Lösung einer Mineralsäure, wie Chlorwasserstoffsäure, Bromwasserstoffsäure, Schwefelsäure oder dergleichen, oder einer organischen Säure, wieThe latter is preferably made by treating the starting material with an aqueous solution of a mineral acid such as hydrochloric acid, hydrobromic acid, sulfuric acid or the like, or an organic acid such as
behandlung wird zweckmässigerweise bei Raumtemperatur durchgeführt, obwohl dies nicht kritisch ist und auch höhere odertreatment is expediently carried out at room temperature, although this is not critical and also higher or
909 8 4 7/1184909 8 4 7/1184
ßAD ORIGiNAL ß AD ORIGiNAL
tiefere Temperatur angewendet werden können. Bs ist selbstverständlich, dass die Temperatur nicht so hoch sein soll, dass eine Zersetzung des gewünschten Bndproduktes eintritt. Bs wurde festgestellt, dass die saure Hydrolyse besonders vorteilhaft ist und stets hohe Ausbeuten liefert. Diese saure Hydrolyse wird zweckmässigerweise in einem wässrigen Medium durchgeführt, das ein organisches Lösungsmittel, wie Dioxan, Tetrahydrofuran oder ähnliche mit Wasser mischbare Lösungsmittel enthält.lower temperature can be used. Bs is a matter of course, that the temperature should not be so high that the desired end product decomposes. Bs was found that acid hydrolysis is particularly advantageous and always gives high yields. This acidic hydrolysis is conveniently carried out in an aqueous medium which is an organic solvent such as dioxane, tetrahydrofuran or similar solvents which are miscible with water.
Verbindungen der Formel I bilden Säureadditionssalze mit sowohl anorganischen als auch organischen Säuren, wie Salzsäure, Bromwasserstoffsäure, Salpetersäure, Schwefelsäure, Phosphorsäure, Citronensäure, Ameisensäure, Essigsäure, Bernsteinsäure , Maleinsäure, Methansulfonsäure, p-Toluolsulfonsäure und dergleichen.Compounds of the formula I form acid addition salts with both inorganic and organic acids, such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, Phosphoric acid, citric acid, formic acid, acetic acid, succinic acid, maleic acid, methanesulfonic acid, p-toluenesulfonic acid and the same.
Die Verbindungen der Formel I können als Sedative, Anticonvulsiva und Muskelrelaxantien verwendet werden. Diese Verbindungen oder ihre pharmazeutische verwendbaren Säureadditionesalze können als Heilmittel z.B. in Form pharmazeutischer Präparate Verwendung finden, welche sie oder ihre Salze in Mischung mit einem für die enterale oder parenterale Applikation geeigneten pharamzeutisehen, organischen oder anorganischen inerten Trägermaterial, wie z.B. Wasser, Gelatine, Milchzukker, Stärke, Magnssiuraatearat, Talk, pflanzliche OeIe, Gummi Polyalkylenglykole, Vaseline, usw. enthalten. Die pharmazeutischen Präparate können in fester Form z.S.'als Tabletten, Dragees, Suppocl+-orbn, ^apseln, oder in flüssiger Form,z.B4 The compounds of formula I can be used as sedatives, anticonvulsants and muscle relaxants. These compounds or their pharmaceutically usable acid addition salts can be used as medicaments, for example in the form of pharmaceutical preparations, which they or their salts in admixture with a pharmaceutical, organic or inorganic inert carrier material suitable for enteral or parenteral administration, such as water, gelatin, milk sugar, Contains starch, magnetic syrup, talc, vegetable oils, gum, polyalkylene glycols, petroleum jelly, etc. The pharmaceutical preparations can be in solid form, e.g. as tablets, coated tablets, Suppocl + -orbn, ^ capsules, or in liquid form, e.g. 4
9098A7/1184 _ _, __9098A7 / 1184 _ _, __
OPiOINALOPiOINAL
als Lösungen, Suspensionen oder Emulsionen, vorliegen. Gegebenenfalls sind sie sterilisiert und bzw. oder enthalten Hilfsstoffe, wie Konservierung-, Stabilieierungs-, Netzoder Emulgiermittel, Salze zur Veränderung des osmotisohen Druckes oder Puffer. Sie können auch noch andere therapeutisch wertvolle Stoffe enthalten.as solutions, suspensions or emulsions. Possibly are they sterilized and / or contain auxiliaries such as preservatives, stabilizers, nets or Emulsifiers, salts to change the osmotic pressure or buffers. You can also do others therapeutically contain valuable substances.
Eine Lösung von 2,0 g 3-Aoetoxy-2-methylamino-7-nitro-5-phenyl-3H-l,4-benzodiazepin in 100 ml Aethanol, das 5 ml 22 #Lge äthanolische Salzsäure enthält,wird 5 Minuten zum Rückfluss erhitzt. Nach dem Einengen auf ein kleines Volumen im Vakuum wird der Rückstand zwischen Chloroform und verdünnter Natriumcarbonatlösung verteilt. Die organische Schicht wird mit Wasser gewaschen, über Natriumsulfat getrocknet filtriert und das Lösungsmittel im Vakuum abdestilliert. Der Rückstand wird aus einer Mischung von Aceton und Hexan umkristallisiert und liefert gelbe Prismen von 3-Aethoxy-2-methylamino-7-nitro-5-phenyl-3H-l,4-benzodiazepin. Durch Umkristallisieren aus einer Mischung von Tetrahydrofuran und Hexan erhält man ein gereinigtes Produkt vom Schmelzpunkt 222-223°. Ausbeute 850 g; 34%.A solution of 2.0 g of 3-aoetoxy-2-methylamino-7-nitro-5-phenyl-3H-1,4-benzodiazepine in 100 ml of ethanol containing 5 ml of 22 #Lge ethanolic hydrochloric acid is refluxed for 5 minutes heated. After concentration to a small volume in vacuo, the residue is diluted between chloroform and dilute Sodium carbonate solution distributed. The organic layer is washed with water, dried over sodium sulfate and filtered the solvent is distilled off in vacuo. The residue is recrystallized from a mixture of acetone and hexane and provides yellow prisms of 3-ethoxy-2-methylamino-7-nitro-5-phenyl-3H-1,4-benzodiazepine. A purified one is obtained by recrystallization from a mixture of tetrahydrofuran and hexane Product with a melting point of 222-223 °. Yield 850 g; 34%.
Das Ausgangsmaterial kann wie folgt erhalten werden:The starting material can be obtained as follows:
Zu einer Lösung von 100 mg 2-Methylamino-7-nitro-5-phenyl-3H-l,4-benzodiazepin-4-oxyd in 5 ml Dimethylformamid setzt man 0,5 ml Acetylchlorid zu. Nach 1-stündigem Rühren bei Raumtemperatur wird die Reaktionsmischung im Vakuum zur Trockene gebracht. Man löst den Rückstand in Aceton und fällt mit wasserfreiem Aether 85 mg rohes 3-Acetcoy-2-methylamino-7-To a solution of 100 mg of 2-methylamino-7-nitro-5-phenyl-3H-1,4-benzodiazepine-4-oxide 0.5 ml of acetyl chloride is added to 5 ml of dimethylformamide. After stirring for 1 hour at The reaction mixture is brought to dryness in vacuo at room temperature. The residue is dissolved in acetone and precipitated with anhydrous ether 85 mg crude 3-Acetcoy-2-methylamino-7-
909847/1184 8AD or,q,nal909847/1184 8AD or, q, nal
nltro-S-phenylOH-l^-benzodiazepln-hydrochlorid. Man verteilt die Substanz zwischen Chloroform und verdünnter Natronlauge. Die organische Schicht wird zweimal mit Wasser gewasuhen, über Natriumsulfat getrocknet, filtriert und Im Vakuum zur Trockene eingeengt. Der RUokstand wird aus einer Mischung von Benzol und Hexan kristallisiert und liefert 3-Acetoxy-2-methylamlno-7-nitro■ 5-phenyl-5H-l,4-benzodlazepln vom Schmelzpunkt 210-212°, das In Büschel von gelben rechteckigen Plättchen kristallisiert. Ausbeutenltro-S-phenylOH-l ^ -benzodiazepln hydrochloride. One distributes the substance between chloroform and dilute sodium hydroxide solution. The organic layer is washed over with water twice Dried sodium sulfate, filtered and concentrated to dryness in vacuo. The raw material is made from a mixture of benzene and Hexane crystallizes and gives 3-acetoxy-2-methylamino-7-nitro ■ 5-phenyl-5H-l, 4-benzodlazepln with a melting point of 210-212 °, the Crystallized in clusters of yellow rectangular platelets. yield
Claims (3)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17855162A | 1962-03-09 | 1962-03-09 | |
| US240750A US3340253A (en) | 1962-11-28 | 1962-11-28 | Preparation of certain benzodiazepine compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1545956A1 true DE1545956A1 (en) | 1969-11-20 |
Family
ID=26874429
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19631545956 Pending DE1545956A1 (en) | 1962-03-09 | 1963-02-23 | Process for the preparation of benzodiazepine derivatives |
| DE19631445873 Pending DE1445873A1 (en) | 1962-03-09 | 1963-02-23 | Process for the preparation of benzodiazepine derivatives |
| DE19631545957 Pending DE1545957A1 (en) | 1962-03-09 | 1963-02-23 | Process for the preparation of benzodiazepine derivatives |
| DE19631545955 Pending DE1545955A1 (en) | 1962-03-09 | 1963-02-23 | Process for the preparation of benzodiazepine derivatives |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19631445873 Pending DE1445873A1 (en) | 1962-03-09 | 1963-02-23 | Process for the preparation of benzodiazepine derivatives |
| DE19631545957 Pending DE1545957A1 (en) | 1962-03-09 | 1963-02-23 | Process for the preparation of benzodiazepine derivatives |
| DE19631545955 Pending DE1545955A1 (en) | 1962-03-09 | 1963-02-23 | Process for the preparation of benzodiazepine derivatives |
Country Status (9)
| Country | Link |
|---|---|
| BE (1) | BE629227A (en) |
| CA (1) | CA976547A (en) |
| CH (2) | CH442326A (en) |
| DE (4) | DE1545956A1 (en) |
| DK (1) | DK127507B (en) |
| ES (1) | ES285854A1 (en) |
| GB (2) | GB1013229A (en) |
| NL (3) | NL7010712A (en) |
| SE (2) | SE328583B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES405260A1 (en) * | 1972-07-28 | 1975-07-01 | Stabilimenti Chim Farmac Riuni | Benzodiazepine compounds for therepeutical use |
| NL173269C (en) * | 1974-04-30 | 1984-01-02 | Ferrer Int | METHOD FOR PREPARING A MEDICINAL PRODUCT WITH THE ACTIVE SUBSTANCE OF A 1,4-BENZODIAZEPINE DERIVATIVE AND METHOD FOR THE PREPARATION OF THE 1,4-BENZODIAZEPINE DERIVATIVE |
| DE3413592C2 (en) * | 1984-04-11 | 1986-06-05 | Dolorgiet GmbH & Co KG, 5205 St Augustin | Medicaments containing 5- (2-fluorophenyl) -1,3-dihydro-3-hydroxy-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one |
| DK287185A (en) * | 1984-06-26 | 1986-02-24 | Merck & Co Inc | BENZODIAZEPINE DERIVATIVE AND PHARMACEUTICAL PREPARATION CONTAINING A SEED ANTI-DERIVATIVE |
-
0
- NL NL289735D patent/NL289735A/xx unknown
-
1963
- 1963-02-21 CH CH222063A patent/CH442326A/en unknown
- 1963-02-21 CH CH1765866A patent/CH457464A/en unknown
- 1963-02-23 DE DE19631545956 patent/DE1545956A1/en active Pending
- 1963-02-23 DE DE19631445873 patent/DE1445873A1/en active Pending
- 1963-02-23 DE DE19631545957 patent/DE1545957A1/en active Pending
- 1963-02-23 DE DE19631545955 patent/DE1545955A1/en active Pending
- 1963-02-27 CA CA869,700A patent/CA976547A/en not_active Expired
- 1963-03-06 BE BE629227A patent/BE629227A/en unknown
- 1963-03-07 GB GB909463A patent/GB1013229A/en not_active Expired
- 1963-03-07 GB GB4791264A patent/GB1013900A/en not_active Expired
- 1963-03-08 SE SE02566/63A patent/SE328583B/xx unknown
- 1963-03-08 ES ES285854A patent/ES285854A1/en not_active Expired
-
1970
- 1970-07-20 NL NL7010712A patent/NL7010712A/xx unknown
- 1970-07-20 NL NL7010711A patent/NL7010711A/xx unknown
- 1970-09-11 SE SE12424/70A patent/SE361174B/xx unknown
-
1972
- 1972-01-18 DK DK25372A patent/DK127507B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SE361174B (en) | 1973-10-22 |
| CH442326A (en) | 1967-08-31 |
| DK127507B (en) | 1973-11-19 |
| BE629227A (en) | 1963-10-21 |
| SE328583B (en) | 1970-09-21 |
| CH457464A (en) | 1968-06-15 |
| CA976547A (en) | 1975-10-21 |
| NL7010711A (en) | 1970-10-26 |
| GB1013229A (en) | 1965-12-15 |
| ES285854A1 (en) | 1963-08-16 |
| NL289735A (en) | |
| DE1445873A1 (en) | 1969-04-10 |
| NL7010712A (en) | 1970-10-26 |
| DE1545957A1 (en) | 1969-12-11 |
| GB1013900A (en) | 1965-12-22 |
| DE1545955A1 (en) | 1969-11-20 |
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| Date | Code | Title | Description |
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| SH | Request for examination between 03.10.1968 and 22.04.1971 |