DE2322573A1 - PROCESS FOR THE PREPARATION OF N-AETHYL2- (2-METHOXY-5-SULFAMOYL-BENZOYL) -METHYLAMINO-PYRROLIDINE - Google Patents
PROCESS FOR THE PREPARATION OF N-AETHYL2- (2-METHOXY-5-SULFAMOYL-BENZOYL) -METHYLAMINO-PYRROLIDINEInfo
- Publication number
- DE2322573A1 DE2322573A1 DE2322573A DE2322573A DE2322573A1 DE 2322573 A1 DE2322573 A1 DE 2322573A1 DE 2322573 A DE2322573 A DE 2322573A DE 2322573 A DE2322573 A DE 2322573A DE 2322573 A1 DE2322573 A1 DE 2322573A1
- Authority
- DE
- Germany
- Prior art keywords
- ethyl
- sulfamoyl
- benzoyl
- methoxy
- pyrrolidine
- 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
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrrole Compounds (AREA)
Description
Luis LEPORI RENAULT, Barcelona / SPANIENLuis LEPORI RENAULT, Barcelona / SPAIN
"Verfahren zur Herstellung von N-Äthyl-2-(2-methoxy-5-sulfamoyl-benzoyl) -methylamino-pyrrolidin""Process for the preparation of N-ethyl-2- (2-methoxy-5-sulfamoyl-benzoyl) -methylamino-pyrrolidine "
PRIORITÄT: 19. Mai 1972 - SPANIEN PRIORITY: May 19, 1972 - SPAIN
Die Erfindung bezieht sich auf ein Verfahren zur Herstellung von N-Äthyl-2-(2-methoxy-5-sulfamoyl-benzoyl)-methylaminopyrrolidin. The invention relates to a process for the preparation of N-ethyl-2- (2-methoxy-5-sulfamoyl-benzoyl) -methylaminopyrrolidine.
Diese Verbindung besitzt eine sehr starke antiemetische Wirkung beim Erbrechen, das durch Apömerphin und Hydergin hervorgerufen wird. Die klinischen Versuche haben gezeigt, daß dieser Stoff besonders wirksam ist bei depressiven, neurotischen Zuständen, bei psychofunktionellen Beschwerden und beiThis compound has a very strong antiemetic effect vomiting caused by apomerphine and hydergine. The clinical trials have shown that this substance is particularly effective in depressive, neurotic states, in psychofunctional complaints and in
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psychischen Rückentwicklungen im Alter. Ausserdem besitzt es eine Wirkung bei Krankheiten wie Magen- und Darmgeschwüren. mental regression in old age. It also has an effect on diseases such as stomach and intestinal ulcers.
Gemäß der Erfindung wird also ein neues Verfahren zur Herstellung von N-Äthyl-2-(2-methoxy-5-sulfamoyl-benzoyl)-methylamino-pyrrolidin vorgeschlagen, welches dadurch ausgeführt wird, daß man zunächst N-Äthyl-2-aminomethylpyrrolidin und aus diesem dann N-Äthyl-2-(2-methoxy-5-sulfamoyl-benzoyl)-methylamino-pyrrolidin herstellt.According to the invention, a new process for the preparation of N-ethyl-2- (2-methoxy-5-sulfamoyl-benzoyl) -methylaminopyrrolidine is provided proposed, which is carried out by first N-ethyl-2-aminomethylpyrrolidine and from this then N-ethyl-2- (2-methoxy-5-sulfamoyl-benzoyl) -methylamino-pyrrolidine manufactures.
Eine bevorzugte Herstellung erfolgt dadurch, daß man N-Äthyl-3-chlorpiperidin mit Ammoniak umsetzt, das erhaltene Produkt mit Orthomethoxybenzoyl Chlorid umsetzt, und das dabei erhaltene Produkt mit Chlorsulfonsäure und dann mit Ammoniak umsetzt.A preferred preparation takes place by using N-ethyl-3-chloropiperidine reacts with ammonia, the product obtained reacts with orthomethoxybenzoyl chloride, and that at the same time product obtained is reacted with chlorosulfonic acid and then with ammonia.
Die erfindungsgemäß herstellbare Verbindung besitzt die FormelThe compound which can be prepared according to the invention has the formula
CO-NH-CH2-CO-NH-CH 2 -
H2NO2SH 2 NO 2 S
Die Herstellung der oben bezeichneten Verbindung erfolgt wie folgt:The connection described above is established as follows:
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a) Herstellung von N-Äthyl-2-aminomethyl-pyrrolidin.a) Production of N-ethyl-2-aminomethyl-pyrrolidine.
Ein 2 Ltr. fassender Dreihalskolben aus Glas, der mit einem Thermometer und einem Rührer versehen ist, wird mit 111 g N-Äthyl-J-chlor-piperidin-chlorhydrat beschickt, welches in 450 ml Ammoniak gelöst ist. Nun wird 6 Stunden auf 1500C erhitzt. Das Lösungsmittel wird abgedampft und der Rückstand wird in einer wäßrigen gesättigten Kaliumcarbonatlösung aufgelöst. Die Lösung wird dreimal mit Chloroform extrahiert und die Chloroformextrakte werden vereinigt. Nach, dem Abdampfen des Chloroforms vom Extrakt bleiben 42,90 g N-Äthyl-2-aminomethyl-pyrrolidin zurück, welches zur Charakterisierung mit äthanolischer Pikrinsäure umgesetzt wird, wobei ein Additionssalz mit einem Schmelzpunkt von 180°C erhalten wird.A 2 liter three-necked glass flask equipped with a thermometer and a stirrer is charged with 111 g of N-ethyl-I-chloropiperidine chlorohydrate, which is dissolved in 450 ml of ammonia. The mixture is then heated to 150 ° C. for 6 hours. The solvent is evaporated and the residue is dissolved in an aqueous saturated potassium carbonate solution. The solution is extracted three times with chloroform and the chloroform extracts are combined. After evaporation of the chloroform from the extract, 42.90 g of N-ethyl-2-aminomethyl-pyrrolidine remain, which is reacted with ethanolic picric acid for characterization, an addition salt with a melting point of 180 ° C. being obtained.
b) Herstellung von N-Äthyl-2-(2-methoxy-5-sulfamoyl-benzoyl)-methylamino-pyrrolidin. b) Preparation of N-ethyl-2- (2-methoxy-5-sulfamoyl-benzoyl) -methylaminopyrrolidine.
40 g des gemäß a) hergestellten N-Äthyl-2-aminomethylpyrrolidin werden in einem Gemisch aus 200 ml Wasser und 200 ml Äthyläther aufgelöst. Bei einer Temperatur von 100C werden gleichzeitig 172 ml 2n NaOH und 56 g Orthomethoxybenzoylchlorid zugegeben, welches vorher in 80 ml Äthyläther Aufgelöst worden war. Das Gemisch wird dann genau 1 Stunde lang in einem Dreihalskolben aus Glas, der einen Thermometer aufweist, gerührt. Mittels eines Scheidetrichters wird, der ätherische Extrakt abgetrennt, der dann mit NapSO^ getrocknet wird. Nach dem Trocknen wird der Äther verdampft. Es bleiben 60 g eines öligen Stoffs zurück, der tropfenweise zu 200 g Chlorsulfonsäure zugegeben wird, die auf 300C gehalten wird. Das Gemisch wird 24- Stunden lang bei Raumtemperatur mechanisch gerührt, worauf dann 800 ml konzentrierter wäßriger Ammoniak bei 10°C zugegeben werden. Nachdem die Temperatur auf Raum-40 g of the N-ethyl-2-aminomethylpyrrolidine prepared according to a) are dissolved in a mixture of 200 ml of water and 200 ml of ethyl ether. At a temperature of 10 ° C., 172 ml of 2N NaOH and 56 g of orthomethoxybenzoyl chloride, which had previously been dissolved in 80 ml of ethyl ether, are added at the same time. The mixture is then stirred for exactly 1 hour in a three-necked glass flask fitted with a thermometer. Using a separating funnel, the essential extract is separated off, which is then dried with NapSO ^. After drying, the ether is evaporated. 60 g of an oily substance remain, which is added dropwise to 200 g of chlorosulfonic acid, which is kept at 30 ° C. The mixture is stirred mechanically for 24 hours at room temperature, after which 800 ml of concentrated aqueous ammonia are added at 10 ° C. After the temperature has reached room
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temperatur angestiegen ist, wird der gebildete Niederschlag abfiltriert. Der Niederschlag wird mit Wasser gewaschen und aus 1n HCl kristallisiert. Das gewonnene Chlorhydrat wird in heißem V/asser aufgelöst und die Lösung wird mit Ammoniak neutralisiert und dann filtriert. Es werden 30,40 g eines Produktes mit einem Schmelzpunkt von 177 bis 179°C erhalten. Das erhaltene N-Äthyl-2-(2-methoxy-5~sulfamoyl-benzoyl)-methylamino-pyrrolidin besitzt die Form eines kristallinen Pulvers.temperature has risen, the precipitate formed is filtered off. The precipitate is washed with water and crystallized from 1N HCl. The obtained chlorohydrate is dissolved in hot water and the solution is neutralized with ammonia and then filtered. There are 30.40 g of a product with a melting point obtained from 177 to 179 ° C. The N-ethyl-2- (2-methoxy-5-sulfamoyl-benzoyl) -methylaminopyrrolidine obtained has the form of a crystalline powder.
Es ist in Wasser fast unlöslich. Säuren und Alkalien lösen den Stoff auf. Er ist ausserdem in Methanol und Äthanol nur schwach und in Chloroform, Benzol und Äthyläther überhaupt nicht löslich.It is almost insoluble in water. Acids and alkalis dissolve the substance. It is also in methanol and ethanol only weakly and not at all soluble in chloroform, benzene and ethyl ether.
PATENTANSPRÜCHE:PATENT CLAIMS:
309847/1134309847/1134
Claims (2)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES403003A ES403003A1 (en) | 1972-05-19 | 1972-05-19 | Method of preparing 2-methoxy-n-n-ethylpyrrolidin-2-yl- methyl-5-sulphamoyl-benzamide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2322573A1 true DE2322573A1 (en) | 1973-11-22 |
Family
ID=8461225
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2322573A Pending DE2322573A1 (en) | 1972-05-19 | 1973-05-04 | PROCESS FOR THE PREPARATION OF N-AETHYL2- (2-METHOXY-5-SULFAMOYL-BENZOYL) -METHYLAMINO-PYRROLIDINE |
Country Status (13)
| Country | Link |
|---|---|
| AR (1) | AR196765A1 (en) |
| AT (1) | AT332387B (en) |
| BE (1) | BE798252A (en) |
| BR (1) | BR7303578D0 (en) |
| CH (1) | CH585713A5 (en) |
| DD (1) | DD106372A5 (en) |
| DE (1) | DE2322573A1 (en) |
| ES (1) | ES403003A1 (en) |
| FR (1) | FR2185621B1 (en) |
| GB (1) | GB1393194A (en) |
| IL (1) | IL42308A0 (en) |
| LU (1) | LU67370A1 (en) |
| NL (1) | NL7306580A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH584688A5 (en) * | 1972-06-23 | 1977-02-15 | Delmar Chem |
-
1972
- 1972-05-19 ES ES403003A patent/ES403003A1/en not_active Expired
-
1973
- 1973-04-06 LU LU67370A patent/LU67370A1/xx unknown
- 1973-04-09 AT AT309973A patent/AT332387B/en not_active IP Right Cessation
- 1973-04-16 BE BE2052692A patent/BE798252A/en unknown
- 1973-05-01 CH CH620773A patent/CH585713A5/xx not_active IP Right Cessation
- 1973-05-04 DE DE2322573A patent/DE2322573A1/en active Pending
- 1973-05-11 NL NL7306580A patent/NL7306580A/xx not_active Application Discontinuation
- 1973-05-14 AR AR248013A patent/AR196765A1/en active
- 1973-05-16 BR BR3578/73A patent/BR7303578D0/en unknown
- 1973-05-18 DD DD170921A patent/DD106372A5/xx unknown
- 1973-05-18 IL IL42308A patent/IL42308A0/en unknown
- 1973-05-18 FR FR7318154A patent/FR2185621B1/fr not_active Expired
- 1973-05-21 GB GB2418973A patent/GB1393194A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| CH585713A5 (en) | 1977-03-15 |
| AR196765A1 (en) | 1974-02-19 |
| FR2185621A1 (en) | 1974-01-04 |
| LU67370A1 (en) | 1973-06-18 |
| ES403003A1 (en) | 1973-06-16 |
| GB1393194A (en) | 1975-05-07 |
| BE798252A (en) | 1973-08-16 |
| DD106372A5 (en) | 1974-06-12 |
| NL7306580A (en) | 1973-11-21 |
| BR7303578D0 (en) | 1974-08-29 |
| IL42308A0 (en) | 1973-07-30 |
| FR2185621B1 (en) | 1976-11-12 |
| AT332387B (en) | 1976-09-27 |
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