CH307541A - Process for the preparation of a tropic acid N- (B-picolyl) -N-alkenyl amide. - Google Patents
Process for the preparation of a tropic acid N- (B-picolyl) -N-alkenyl amide.Info
- Publication number
- CH307541A CH307541A CH307541DA CH307541A CH 307541 A CH307541 A CH 307541A CH 307541D A CH307541D A CH 307541DA CH 307541 A CH307541 A CH 307541A
- Authority
- CH
- Switzerland
- Prior art keywords
- picolyl
- tropic acid
- alkenyl
- preparation
- sep
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 4
- JACRWUWPXAESPB-QMMMGPOBSA-N Tropic acid Natural products OC[C@H](C(O)=O)C1=CC=CC=C1 JACRWUWPXAESPB-QMMMGPOBSA-N 0.000 title description 4
- VBSTXRUAXCTZBQ-UHFFFAOYSA-N 1-hexyl-4-phenylpiperazine Chemical compound C1CN(CCCCCC)CCN1C1=CC=CC=C1 VBSTXRUAXCTZBQ-UHFFFAOYSA-N 0.000 title description 3
- 238000002360 preparation method Methods 0.000 title description 2
- 150000001412 amines Chemical class 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000000155 melt Substances 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims 1
- 150000004820 halides Chemical class 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- -1 0-acylated tropic acid halide Chemical class 0.000 description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 4
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- WMXURTHCVUXSGD-UHFFFAOYSA-N 2-(hydroxymethyl)-3-oxo-2-phenylbutanoyl chloride Chemical compound CC(=O)C(CO)(C(Cl)=O)C1=CC=CC=C1 WMXURTHCVUXSGD-UHFFFAOYSA-N 0.000 description 1
- SVODWEGGIIFGHZ-UHFFFAOYSA-N 3-(chloromethyl)pyridine;hypochlorous acid Chemical compound ClO.ClCC1=CC=CN=C1 SVODWEGGIIFGHZ-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- HSNRTOUAJIOGML-UHFFFAOYSA-N [1-(4-methylphenyl)sulfonyl-2H-pyridin-3-yl]methanamine Chemical compound C1(=CC=C(C=C1)S(=O)(=O)N1CC(=CC=C1)CN)C HSNRTOUAJIOGML-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000005881 detosylation reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/40—Acylated substituent nitrogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
<B>Verfahren zur Herstellung eines</B> Tropasäure-N-(ss-picolyl)-N-alkenylamides. Es wurde gefunden, dass Tropasäureamide- der allgemeinen Formel
EMI0001.0004
in der R einen Alkenylrest, z. B. eine Allyl- gruppe, bedeutet, gute spasmolytische Eigen- sehaften zeigen.
Die neuen Verbindungen werden erfin dungsgemäss durch Kondensation eines gege benenfalls 0-acylierten Tropasäurehalogenids mit einem Alkenyl-(f-picolyl)-amin, gegebe nenfalls gefolgt von der Abspaltung der 0-Acylgruppe, hergestellt.
Die Alkenyl-(ss-picolyl)-amine können bei spielsweise durch Umsetzung von 3-Halogen- methyl-pyridin mit einem primären Alkenyl- amin oder durch Alkenylierung von N-(p-To- luolsulfonyl)-3-aminomethyl-pyridin mit einem Alkenylhalogenid oder Alkenylsulfat und nach folgende Enttosylierung gewonnen werden.
Gegenstand des Patentes ist ein Verfah ren zur Herstellung eines Tropasäure-N-alke- nyl-N-(ss-picolyl)-amides, das dadurch gekenn zeichnet ist, dass man ein Acyltropasäurehalo- genid mit Allyl-(ss-picolyl)-amin umsetzt und die 0-Acylgruppe abspaltet.
Beispiel: Unter Schütteln fügt man eine Lösung von 32,8 Gewichtsteilen 3-Chlormethyl-pyri- din-chlorhydrat in 40 Gewichtsteilen Wasser nach und nach in 70 Gewichtsteile Allylamin, wobei die Temperatur unterhalb 10 C gehal ten wird. Man schüttelt noch zwei Stunden bei Raumtemperatur, dann eine weitere Stunde bei 40 C, kühlt mit Eis und sättigt mit festem Kaliumhydroxyd. Die obere Schicht trennt man ab.
Beim Destillieren der letzteren geht zuerst unter gewöhnlichem Druck das nicht umgesetzte Allylamin und dann bei 120 C unter einem Drucke von 13 mm Rg das Allyl- (ss-picolyl)-amin über.
Zu einer Mischung von 74 Gewichtsteilen Allyl-(ss-picolyl)-amin (Kp.13 120 C) und 45 Gewichtsteilen trockenem Pyridin in 250 Ge wichtsteilen trockenem Chloroform wird rohes, aus 85 Gewichtsteilen Tropasäure durch Ein- wirkung von Acetylchlorid und anschliessen der Behandlung mit überschüssigem Thionyl- chlorid erhaltenes Acetyltropasäurechlorid un ter Rühren und Eiswasserkühlung nach und nach zugegeben.
Zum Schluss wird noch eine Stunde bei gewöhnlicher Temperatur gerührt.
Dann wird die Chloroformlösung mit 250 Gewichtsteilen Äther verdünnt und mit 3n- Salzsäure geschüttelt. Die schwach kongosaure Lösung wird eine Stunde lang auf dem Dampf bad erwärmt, wobei die Acetylgruppe des Re aktionsproduktes abgespalten wird. Man fil triert über Kohle und versetzt mit überschüs sigem, konzentriertem Ammoniak.
Das ausge fallene Kondensationsprodukt wird in Chloro form aufgenommen, das Chloroform getrock net und destilliert. Das zurückbleibende
EMI0002.0001
Tropasäiire-N-allyl-N-(,B-picolyl)-amid <SEP> stellt
<tb> ein <SEP> dickflüssiges <SEP> Öl <SEP> dar, <SEP> dessen <SEP> Chlorhydrat
<tb> bei <SEP> 136-137 <SEP> C <SEP> schmilzt.
<B> Process for the preparation of </B> a tropic acid-N- (ss-picolyl) -N-alkenylamide. It has been found that tropic acid amide- of the general formula
EMI0001.0004
in R is an alkenyl radical, e.g. B. an allyl group, means showing good spasmolytic properties.
The new compounds are in accordance with the invention by condensation of an optionally 0-acylated tropic acid halide with an alkenyl- (f-picolyl) -amine, optionally followed by the cleavage of the 0-acyl group.
The alkenyl (ss-picolyl) amines can, for example, by reacting 3-halomethyl-pyridine with a primary alkenyl amine or by alkenylating N- (p-toluenesulfonyl) -3-aminomethyl-pyridine with a Alkenyl halide or alkenyl sulfate and can be obtained after subsequent detosylation.
The subject of the patent is a process for the production of a tropic acid-N-alkenyl-N- (ss-picolyl) amide, which is characterized in that an acyl tropic acid halide is mixed with allyl (ss-picolyl) amine converts and splits off the 0-acyl group.
Example: A solution of 32.8 parts by weight of 3-chloromethylpyridine chlorohydrate in 40 parts by weight of water is gradually added to 70 parts by weight of allylamine with shaking, the temperature being kept below 10 ° C. It is shaken for a further two hours at room temperature, then for a further hour at 40 ° C., cooled with ice and saturated with solid potassium hydroxide. The upper layer is separated.
When the latter is distilled, the unreacted allylamine first passes over under normal pressure and then the allyl (ss-picolyl) amine at 120 ° C. under a pressure of 13 mm Rg.
To a mixture of 74 parts by weight of allyl (ss-picolyl) amine (bp 13 120 C) and 45 parts by weight of dry pyridine in 250 parts by weight of dry chloroform is crude, from 85 parts by weight of tropic acid by the action of acetyl chloride and subsequent treatment Acetyltropic acid chloride obtained with excess thionyl chloride was gradually added with stirring and ice-water cooling.
Finally, the mixture is stirred for another hour at normal temperature.
Then the chloroform solution is diluted with 250 parts by weight of ether and shaken with 3N hydrochloric acid. The weakly Congo acidic solution is heated for one hour on the steam bath, whereby the acetyl group of the reaction product is split off. It is filtered over charcoal and treated with excess concentrated ammonia.
The precipitated condensation product is taken up in chloroform, the chloroform net getrock and distilled. What remains
EMI0002.0001
Tropasäiire-N-allyl-N - (, B-picolyl) -amid <SEP> represents
<tb> is a <SEP> viscous <SEP> oil <SEP>, <SEP> its <SEP> chlorohydrate
<tb> at <SEP> 136-137 <SEP> C <SEP> melts.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH281901T | 1950-04-25 | ||
| CH307541T | 1952-02-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH307541A true CH307541A (en) | 1955-05-31 |
Family
ID=4483397
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH281901D CH281901A (en) | 1950-04-25 | 1950-04-25 | Process for the preparation of a new tropic acid derivative. |
| CH307541D CH307541A (en) | 1950-04-25 | 1952-02-06 | Process for the preparation of a tropic acid N- (B-picolyl) -N-alkenyl amide. |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH281901D CH281901A (en) | 1950-04-25 | 1950-04-25 | Process for the preparation of a new tropic acid derivative. |
Country Status (5)
| Country | Link |
|---|---|
| AT (2) | AT170881B (en) |
| CH (2) | CH281901A (en) |
| DE (1) | DE834102C (en) |
| DK (1) | DK79518C (en) |
| FR (1) | FR1031904A (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE961347C (en) * | 1952-02-06 | 1957-04-04 | Hoffmann La Roche | Process for the preparation of tropic acid-N- (‰ ‰ -picolyl) -amides which are further substituted on the amide nitrogen |
| DE960634C (en) * | 1952-10-24 | 1957-03-28 | Hoffmann La Roche | Process for the preparation of substituted tropic acid-N- (ª † -picolyl) -amides |
| DE952808C (en) * | 1954-03-05 | 1956-11-22 | Hoffmann La Roche | Process for the production of a new tropasaeuramide |
| DE965239C (en) * | 1954-04-24 | 1957-06-06 | Hoffmann La Roche | Process for the preparation of tropic acid-N-alkyl-N- (ª † -picolyl) -amides |
| DE1058512B (en) * | 1954-09-24 | 1959-06-04 | Hoffmann La Roche | Process for the preparation of methyl-(ª-picolyl)-amine |
| DE1142614B (en) * | 1957-05-31 | 1963-01-24 | Koninklijke Pharma Fab Nv | Process for the production of benzhydryl ethers of tropine, their salts and quaternary ammonium compounds |
| RU2006116421A (en) * | 2003-11-25 | 2008-01-10 | Ново Нордиск А/С (DK) | SALICYLIC ACID ANILIDES |
-
1950
- 1950-04-25 CH CH281901D patent/CH281901A/en unknown
- 1950-12-29 DE DEH7112A patent/DE834102C/en not_active Expired
-
1951
- 1951-01-03 AT AT170881D patent/AT170881B/en active
- 1951-01-03 DK DK1651A patent/DK79518C/en active
- 1951-01-31 FR FR1031904D patent/FR1031904A/en not_active Expired
-
1952
- 1952-02-06 CH CH307541D patent/CH307541A/en unknown
- 1952-12-16 AT AT178354D patent/AT178354B/en active
Also Published As
| Publication number | Publication date |
|---|---|
| AT178354B (en) | 1954-05-10 |
| FR1031904A (en) | 1953-06-29 |
| CH281901A (en) | 1952-03-31 |
| DK79518C (en) | 1955-07-11 |
| DE834102C (en) | 1952-03-17 |
| AT170881B (en) | 1952-04-10 |
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