CH298775A - Process for preparing an antihistamine substance. - Google Patents
Process for preparing an antihistamine substance.Info
- Publication number
- CH298775A CH298775A CH298775DA CH298775A CH 298775 A CH298775 A CH 298775A CH 298775D A CH298775D A CH 298775DA CH 298775 A CH298775 A CH 298775A
- Authority
- CH
- Switzerland
- Prior art keywords
- amine
- preparing
- pyridyl
- chlorophenyl
- antihistamine substance
- Prior art date
Links
- 239000000126 substance Substances 0.000 title claims description 5
- 238000004519 manufacturing process Methods 0.000 title claims 2
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 title description 3
- 230000001387 anti-histamine Effects 0.000 title description 3
- 239000000739 antihistaminic agent Substances 0.000 title description 3
- 150000001412 amines Chemical class 0.000 claims description 5
- 238000009835 boiling Methods 0.000 claims description 5
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- -1 amine salt Chemical class 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 125000002560 nitrile group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229940075930 picrate Drugs 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- ZUHZZVMEUAUWHY-UHFFFAOYSA-N n,n-dimethylpropan-1-amine Chemical compound CCCN(C)C ZUHZZVMEUAUWHY-UHFFFAOYSA-N 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 238000003756 stirring Methods 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
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Description
<B>Procédé de préparation</B> d'une substance antihistaminique. La présente invention concerne un procédé de préparation d'une nouvelle substance anti histaminique, la 3-(p-chlorophényl)-3-(pyri- dyl-2)-N,1V diméthyl-propylamine, ce procédé étant caractérisé en ce qu'on fait réagir le (p - chlorophényl) - (P.-diméthylaminoéthyl)- (pyridyl-2)
-acétonitrile avec un acide fort contenant suffisamment d'eau pour hydroly ser le groupe nitrile en groupe carboxyle, et qu'on transforme ensuite, le sel d'amine décar- boxylé ainsi obtenu en amine libre par traite ment avec un alcali. La substance nouvelle est un liquide huileux à point d'ébullition de 153-158 C/2-3 mm.
<I>Exemple 1:</I> On ajoute 2000 g d'acide sulfurique à 80% à 400g de (p-chlorophényl)-(fl-âiméthylamino- éthyl)-(pyridyl-2)-acétonitrile. On chauffe le mélange, en l'agitant, à 140-150 C pendant 24 heures.
Après décomposition avec de la glace et de l'eau, on rend alcaline la solution aqueuse d'acide sulfurique avec du gaz ammo- nia.c. On extrait avec de l'éther l'huile qui se sépare, on sèche l'extrait et, après avoir éli miné l'éther, on distille le résidu et on obtient la 3-(p-chlorophényl)-3- (pyridyl-2)-N,N-di- méthyl-propylamine, bouillant à une tempe'- rature de, 153-1580 C/2-3 mm.
<I>Exemple 2:</I> On soumet au reflux pendant 50 à 60 heu res une partie du nitrile de l'exemple 1 et 10 parties d'acide bromhydrique à 48 0/0; on éli- mine l'acide bromhydrique aqueux dans le vide; on rend le résidu alcalin par le -gaz ammoniac et on extrait avec de l'éther l'huile qui se sépare. On traite le résidu de cette extraction à l'éther avec une solution alcooli que saturée d'acide picrique chauffée à ébulli tion et on filtre. On lave le picrate insoluble avec de l'alcool bouillant.
Cette opération. de purification élimine la matière première qui, à l'encontre de l'amine, forme un-picrate so luble dans l'alcool. Puis on décompose le pi crate insoluble avec une solution diluée de soude caustique, on isole l'amine par extrac tion avec de.l'éther et on la purifie encore par distillation.
<I>Exemple 3:</I> _ On ajoute à 1 partie du nitrile de l'exem- ple 1 5 parties d'acide sulfurique à 80 % et 1 partie d'acide bromhydrique à 48 %. On chauffe le mélange à une température de 130-140 C pendant environ. 30 à 40 heures et.
on traite le mélange de la réaction comme dans. l'exemple 2.
Exemple <I>4:</I> On sommet au reflux une partie du nitrile de l'exemple 1 avec de l'acide .chlorhydrique concentré pendant environ 60 heures. On li bère l'amine ainsi formée et on la purifie de la manière indiquée dans l'exemple 2.
<B> Process for the preparation </B> of an antihistamine substance. The present invention relates to a process for the preparation of a novel antihistamine substance, 3- (p-chlorophenyl) -3- (pyridyl-2) -N, 1V dimethyl-propylamine, this process being characterized in that reacting (p - chlorophenyl) - (P.-dimethylaminoethyl) - (pyridyl-2)
-acetonitrile with a strong acid containing sufficient water to hydrolyze the nitrile group to a carboxyl group, and then converting the decarboxylated amine salt thus obtained into the free amine by treatment with an alkali. The new substance is an oily liquid with a boiling point of 153-158 C / 2-3 mm.
<I> Example 1: </I> 2000 g of 80% sulfuric acid are added to 400 g of (p-chlorophenyl) - (fl-âimethylamino-ethyl) - (pyridyl-2) -acetonitrile. The mixture is heated, with stirring, at 140-150 ° C. for 24 hours.
After decomposing with ice and water, the aqueous solution of sulfuric acid is made alkaline with ammonia gas. The oil which separates is extracted with ether, the extract is dried and, after removing the ether, the residue is distilled off and 3- (p-chlorophenyl) -3- (pyridyl-) is obtained. 2) -N, N-dimethyl-propylamine, boiling at a temperature of, 153-1580 C / 2-3 mm.
<I> Example 2: </I> Part of the nitrile of Example 1 and 10 parts of 48% hydrobromic acid are subjected to reflux for 50 to 60 hours; aqueous hydrobromic acid is removed in vacuo; the residue is made alkaline with ammonia gas and the oil which separates is extracted with ether. The residue of this ether extraction is treated with a saturated alcoholic picric acid solution heated to boiling and filtered. The insoluble picrate is washed with boiling alcohol.
This operation. purification removes the raw material which, unlike the amine, forms a soluble un-picrate in alcohol. Then, the insoluble salt is decomposed with dilute caustic soda solution, the amine is isolated by extraction with ether and further purified by distillation.
<I> Example 3: </I> _ To 1 part of the nitrile of Example 1 5 parts of 80% sulfuric acid and 1 part of 48% hydrobromic acid are added. The mixture is heated to a temperature of 130-140 C for approximately. 30 to 40 hours and.
the reaction mixture is treated as in. example 2.
Example <I> 4: </I> Part of the nitrile of Example 1 is refluxed with concentrated hydrochloric acid for about 60 hours. The amine thus formed is released and purified in the manner indicated in Example 2.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH298775T | 1951-02-28 | ||
| CH282219T | 1951-02-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH298775A true CH298775A (en) | 1954-05-15 |
Family
ID=25732164
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH298775D CH298775A (en) | 1951-02-28 | 1951-02-28 | Process for preparing an antihistamine substance. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH298775A (en) |
-
1951
- 1951-02-28 CH CH298775D patent/CH298775A/en unknown
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