CH298685A - Process for the preparation of a novel derivative of phenothiazine. - Google Patents
Process for the preparation of a novel derivative of phenothiazine.Info
- Publication number
- CH298685A CH298685A CH298685DA CH298685A CH 298685 A CH298685 A CH 298685A CH 298685D A CH298685D A CH 298685DA CH 298685 A CH298685 A CH 298685A
- Authority
- CH
- Switzerland
- Prior art keywords
- phenothiazine
- preparation
- chloro
- propyl
- novel derivative
- Prior art date
Links
- 238000000034 method Methods 0.000 title description 5
- 125000001484 phenothiazinyl group Chemical class C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 title 1
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 10
- 229950000688 phenothiazine Drugs 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
- 239000000155 melt Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- -1 aliphatic alcohols Chemical class 0.000 description 3
- 150000002990 phenothiazines Chemical class 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- TUZVTRCMDIUEBE-UHFFFAOYSA-N 1-chloro-10h-phenothiazine Chemical compound S1C2=CC=CC=C2NC2=C1C=CC=C2Cl TUZVTRCMDIUEBE-UHFFFAOYSA-N 0.000 description 1
- WLXGQMVCYPUOLM-UHFFFAOYSA-N 1-hydroxyethanesulfonic acid Chemical compound CC(O)S(O)(=O)=O WLXGQMVCYPUOLM-UHFFFAOYSA-N 0.000 description 1
- NQCQVNHLNXCSPY-UHFFFAOYSA-N 3-chloropropyl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(S(=O)(=O)OCCCCl)C=C1 NQCQVNHLNXCSPY-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000000219 Sympatholytic Substances 0.000 description 1
- 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 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 230000002005 ganglioplegic effect Effects 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 229940005494 general anesthetics Drugs 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229940075930 picrate Drugs 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
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 230000000948 sympatholitic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Procédé de préparation d'un nouveau dérivé de la phénothiazine. La présente invention a pour objet un procédé de préparation d'un nouveau dérivé de la phénothiazine, la chloro-3-(diméthyl- amino-3'-propyl)-10-phénothia.zine répondant à la formule:
EMI0001.0006
Le procédé selon la présente invention est caractérisé en ce que l'on fait réagir la di- méthylamine sur une chloro-3-(halogéno-3,'- propyl) -10-phénothiazine.
La réaction de la diméthylamine sur la chloro-3- (halogéno-3'-propyl) -10-phénothiazine est avantageusement réalisée en autoclave, de préférence à une température de 100-150 . On peut également opérer à température ordi naire, mais la réaction est beaucoup phis lente. On peut travailler avec ou sans solvant, mais il est préférable d'utiliser un solvant du groupe des alcools aliphatiques ou mieux des carbures aromatiques.
La chloro-3-(diméthylamino-3'-propyl)-10- phénothiazine obtenue par le procédé de l'in vention est une nouvelle substance dont le chlorhydrate fond à 177-178 C. Elle possède des propriétés physiologiques précieuses, qui permettent de l'utiliser comme antihistamini- que, ganglioplégique, spasmolytique, anesthé sique local, analgésique, sympatholytique, antifungique. Enfin, elle s'est révélée particu lièrement intéressante comme potentialisateur des anesthésiques généraux, des analgésiques et des anesthésiques locaux.
<I>Exemple:</I> On mélange 31 g de cbloro-3- (cblor o-3'- propyl)-10-phénothiazine brute avec 50 em3 de solution alcoolique de diméthylamine à 30 1/o et on chauffe le tout en tube scellé pen dant 7 heures à 120 . On chasse ensuite l'al cool et l'excès de diméthylamine, reprend par l'eau acidulée et filtre. On alcalinise à la soude et extrait à l'éther.
On chasse l'éther et rectifie; on obtient la chloro-3-(diméthyl- amino - 3'- propyl) -10 - phénothiazine Eb. 0,8 = 200-210 , dont le chlorhydrate fond à 177-178 , le picrate de couleur rouge à 169 et le méthylsulfométhylate à 140-141 . La chloro-3- (chloro-3'-propyl)-10-phénothiazine a été préparée par analogie avec la méthode décrite par Gilman et Shirley Am.
Soc. 66 890 (1944), par action du p-toluène-sulfonate de y-chloropropyle sur la chlorophénothiazine lithique.
Process for the preparation of a novel derivative of phenothiazine. The present invention relates to a process for preparing a novel derivative of phenothiazine, chloro-3- (dimethyl-amino-3'-propyl) -10-phenothia.zine corresponding to the formula:
EMI0001.0006
The process according to the present invention is characterized in that the dimethylamine is reacted with a chloro-3- (halogeno-3, '- propyl) -10-phenothiazine.
The reaction of dimethylamine with chloro-3- (halogeno-3'-propyl) -10-phenothiazine is advantageously carried out in an autoclave, preferably at a temperature of 100-150. It is also possible to operate at ordinary temperature, but the reaction is very slow. It is possible to work with or without a solvent, but it is preferable to use a solvent from the group of aliphatic alcohols or better still of aromatic carbides.
Chloro-3- (dimethylamino-3'-propyl) -10-phenothiazine obtained by the process of the invention is a new substance whose hydrochloride melts at 177-178 C. It has valuable physiological properties, which make it possible to use it as an antihistamine, ganglioplegic, spasmolytic, local anesthesia, analgesic, sympatholytic, antifungal. Finally, it has proved to be particularly interesting as a potentiator of general anesthetics, analgesics and local anesthetics.
<I> Example: </I> 31 g of crude cbloro-3- (cblor o-3'-propyl) -10-phenothiazine are mixed with 50 em3 of alcoholic solution of dimethylamine at 30 1 / o and the whole is heated in sealed tube for 7 hours at 120. The alcohol is then removed and the excess of dimethylamine, taken up in acidulated water and filtered. It is basified with sodium hydroxide and extracted with ether.
The ether is driven out and rectified; chloro-3- (dimethylamino - 3'-propyl) -10 - phenothiazine Eb. 0.8 = 200-210, of which the hydrochloride melts at 177-178, the red colored picrate at 169 and the methylsulfomethoxide at 140-141. Chloro-3- (chloro-3'-propyl) -10-phenothiazine was prepared by analogy with the method described by Gilman and Shirley Am.
Soc. 66890 (1944), by the action of γ-chloropropyl p-toluenesulphonate on lithic chlorophenothiazine.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR298685X | 1951-06-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH298685A true CH298685A (en) | 1954-05-15 |
Family
ID=8888327
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH298685D CH298685A (en) | 1951-06-28 | 1951-11-16 | Process for the preparation of a novel derivative of phenothiazine. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH298685A (en) |
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1051858B (en) * | 1957-04-27 | 1959-03-05 | Knoll Ag | Process for the production of pellets of phenthiazine |
| DE1056611B (en) * | 1955-11-15 | 1959-05-06 | Rhone Poulenc Sa | Process for the preparation of phenthiazine derivatives |
| DE1058998B (en) * | 1955-11-25 | 1959-06-11 | Rhone Poulenc Sa | Process for the preparation of phenthiazine derivatives |
| DE1059460B (en) * | 1956-01-10 | 1959-06-18 | Rhone Poulenc Sa | Process for the preparation of phenthiazine derivatives |
| DE1087605B (en) * | 1958-03-29 | 1960-08-25 | Knoll Ag | Process for the preparation of phenthiazine derivatives |
| DE1088964B (en) * | 1956-08-01 | 1960-09-15 | Rhone Poulenc Sa | Process for the preparation of phenthiazine derivatives |
| DE1124500B (en) * | 1956-06-21 | 1962-03-01 | Searle & Co | Process for the preparation of 3-chloro-10-{ª[N'-(ª''-acetoxyaethyl)-piperazino]-propyl}-phenthiazine and its salts |
| DE1128856B (en) * | 1956-04-18 | 1962-05-03 | Sandoz Ag | Process for the preparation of phenthiazine derivatives substituted in the 3-position by sulfur-containing groups |
| DE1131680B (en) * | 1956-07-18 | 1962-06-20 | Rhone Poulenc Sa | Process for the preparation of phenthiazine derivatives |
| DE1134992B (en) * | 1958-09-10 | 1962-08-23 | Geigy Ag J R | Process for the preparation of basic substituted phenthiazines |
| DE1137734B (en) * | 1958-09-03 | 1962-10-11 | Spofa Vereinigte Pharma Werke | Process for the preparation of basic 1,3-dihalophen-thiazine derivatives |
| DE1138779B (en) * | 1956-04-09 | 1962-10-31 | Smith Klme &- French Laborato rxes Philadelphia Pa (V St A) | Process for the preparation of 10- (aminoalkyl) -trifluoromethyl-phenthiazine derivatives substituted in the amino group. |
| DE1141286B (en) * | 1956-08-09 | 1962-12-20 | Scherico Ltd | Process for the preparation of phenthiazine derivatives |
| DE1151509B (en) * | 1955-03-19 | 1963-07-18 | Scherico Ltd | Process for the preparation of phenthiazine derivatives |
| DE1153020B (en) * | 1955-06-30 | 1963-08-22 | Clin Byla Ets | Process for the preparation of phenthiazine derivatives |
| DE1173099B (en) * | 1957-06-10 | 1964-07-02 | Smith Kline French Lab | Process for the preparation of trifluoromethylsulfonyl-phenthiazines with basic substitution in the 10-position |
| DE1181709B (en) * | 1957-06-18 | 1964-11-19 | Smith Kline French Lab | Process for the preparation of phenthiazines with basic substitution in the 10-position |
-
1951
- 1951-11-16 CH CH298685D patent/CH298685A/en unknown
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1151509B (en) * | 1955-03-19 | 1963-07-18 | Scherico Ltd | Process for the preparation of phenthiazine derivatives |
| DE1153020B (en) * | 1955-06-30 | 1963-08-22 | Clin Byla Ets | Process for the preparation of phenthiazine derivatives |
| DE1056611B (en) * | 1955-11-15 | 1959-05-06 | Rhone Poulenc Sa | Process for the preparation of phenthiazine derivatives |
| DE1058998B (en) * | 1955-11-25 | 1959-06-11 | Rhone Poulenc Sa | Process for the preparation of phenthiazine derivatives |
| DE1059460B (en) * | 1956-01-10 | 1959-06-18 | Rhone Poulenc Sa | Process for the preparation of phenthiazine derivatives |
| DE1138779B (en) * | 1956-04-09 | 1962-10-31 | Smith Klme &- French Laborato rxes Philadelphia Pa (V St A) | Process for the preparation of 10- (aminoalkyl) -trifluoromethyl-phenthiazine derivatives substituted in the amino group. |
| DE1128856B (en) * | 1956-04-18 | 1962-05-03 | Sandoz Ag | Process for the preparation of phenthiazine derivatives substituted in the 3-position by sulfur-containing groups |
| DE1124500B (en) * | 1956-06-21 | 1962-03-01 | Searle & Co | Process for the preparation of 3-chloro-10-{ª[N'-(ª''-acetoxyaethyl)-piperazino]-propyl}-phenthiazine and its salts |
| DE1131680B (en) * | 1956-07-18 | 1962-06-20 | Rhone Poulenc Sa | Process for the preparation of phenthiazine derivatives |
| DE1088964B (en) * | 1956-08-01 | 1960-09-15 | Rhone Poulenc Sa | Process for the preparation of phenthiazine derivatives |
| DE1141286B (en) * | 1956-08-09 | 1962-12-20 | Scherico Ltd | Process for the preparation of phenthiazine derivatives |
| DE1051858B (en) * | 1957-04-27 | 1959-03-05 | Knoll Ag | Process for the production of pellets of phenthiazine |
| DE1173099B (en) * | 1957-06-10 | 1964-07-02 | Smith Kline French Lab | Process for the preparation of trifluoromethylsulfonyl-phenthiazines with basic substitution in the 10-position |
| DE1181709B (en) * | 1957-06-18 | 1964-11-19 | Smith Kline French Lab | Process for the preparation of phenthiazines with basic substitution in the 10-position |
| DE1087605B (en) * | 1958-03-29 | 1960-08-25 | Knoll Ag | Process for the preparation of phenthiazine derivatives |
| DE1137734B (en) * | 1958-09-03 | 1962-10-11 | Spofa Vereinigte Pharma Werke | Process for the preparation of basic 1,3-dihalophen-thiazine derivatives |
| DE1134992B (en) * | 1958-09-10 | 1962-08-23 | Geigy Ag J R | Process for the preparation of basic substituted phenthiazines |
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