Tolterodine

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Achtung

• Gefahrenhinweise

  H301：Giftig bei Verschlucken.

  H361：Kann vermutlich die Fruchtbarkeit beeinträchtigen oder das Kind im Mutterleib schädigen.

• Sicherheit

  P281：Vorgeschriebene persönliche Schutzausrüstung verwenden.

  P301+P310：BEI VERSCHLUCKEN: Sofort GIFTINFORMATIONSZENTRUM/Arzt/... (geeignete Stelle für medizinische Notfallversorgung vom Hersteller/Lieferanten anzugeben) anrufen.

Tolterodine Chemische Eigenschaften,Einsatz,Produktion Methoden

• Chemische Eigenschaften

  Pale Yellow Gel

• Originator

  Detrol,Pharmacia and Upjohn

• Verwenden

  A muscarinic receptor antagonist. Used in the treatment of urinary incontinence.

• Definition

  ChEBI: Tolterodine is a tertiary amine. It has a role as a muscarinic antagonist, a muscle relaxant and an antispasmodic drug. It is functionally related to a p-cresol.

• Manufacturing Process

  Trans-cinnamic acid (100 g, 675 mmol) is added to a 1 L 4-neck round bottom flask equipped with a mechanical stirrer, thermocouple, and nitrogen inlet. Para-cresol (76.6 g, 708 mmol) is preheated in a water bath at 60°C and added to the cinnamic acid followed by concentrated sulfuric acid (13.0 ml, 243 mmol). The reaction is immediately heated to a set point of 122.5°C and stirred at 120°-125°C until judged to be complete by HPLC analysis. When the reaction is complete the mixture is cooled to 100°C and added to a prewarmed separatory funnel (500 ml). The bottom layer containing the sulfuric acid is removed and toluene (280 ml), water (50 ml) and potassium carbonate (47%, 10 ml) are added to the separatory funnel containing the crude product. The pH of the aqueous layer is adjusted to between 5-8 with additional 47% potassium carbonate. The layers are separated and the organic layer is then washed once with water (50 ml). The organic layer is concentrated to a final volume of approximately 150 ml under reduced pressure. Isopropanol (350 ml) is then added, and distillation is continued to a volume of 350 ml. Isopropanol (150 ml) is again added and again distilled to 350 ml (2 times). The mixture is then cooled to 30°-40°C with rapid stirring until the product crystallizes. The rapid stirring is continued after crystallization. The product is cooled to 0°-5°C and held at this temperature for 1 h, filtered and washed with isopropanol (200 ml) cooled to 0°-5°C. If the last portion of the wash is colored the wash is continued until no more color is removed. The solids are then dried at 60°C under reduced pressure to give the 3,4-dihydro-6-methyl-4-phenyl-2H-benzopyran-2-one, melting point (uncorrected) 83°-85°C.
  3,4-Dihydro-6-methyl-4-phenyl-2H-benzopyran-2-one (100.0 g, 420.2 mmol) is added to toluene (500 ml). The mixture is degassed by purging alternately with vacuum and nitrogen and then cooled to -21°C. Diisobutylaluminum hydride in toluene solution (DIBAL, 1.5 M, 290 ml, 435 mmol) is then slowly added over 2 h via add funnel while maintaining the reaction temperature at - 20°-25°C. The reaction is usually done when the DIBAL add is completed. If the reaction is not done additional DIBAL can be added in increments. When the reaction is done (<1% lactone) ethyl acetate (45 ml) is added at -20°- 25°C via add funnel. Very little exotherm is observed. Next, citric acid (23%, 500 ml) is added. The mixture is stirred at 45°-50°C for 1 h (or stirred overnight at 20°-25°C), the phases are separated, the organic phase is washed with water (2 times 300 ml). The organic phase is concentrated to 250 ml under reduced pressure. Methanol (500 ml) is added, and the mixture is concentrated to 250 ml. The methanol addition and distillation is repeated to give the 3,4-dihydro-6-methyl-4-phenyl-2H-benzopyran-2-ol in methanol solution.
  3,4-Dihydro-6-methyl-4-phenyl-2H-benzopyran-2-ol in methanol (500 ml) is slowly added to palladium on carbon (5%, 22 g, 1.5 mmol) while maintaining a slight nitrogen purge. If 3,4-dihydro-6-methyl-4-phenyl-2H-benzopyran-2-ol is added too quickly without a nitrogen purge the catalyst will ignite the methanol. Diisopropylamine (147.0 ml, 1.05 mol) is added, and the mixture is hydrogenated at 45-50 psi and 48°C until the reaction is judged to be complete by HPLC (<2% lactol). The reaction is usually done after 10 h, but can be run overnight. The reaction mixture is cooled and removed from the hydrogenator using a methanol (150 ml) rinse. The combined reaction mixture and rinse is filtered through a bed of solka floc (10 g). The solka floc is washed thoroughly with methanol (100 ml) and the filtrate is concentrated to remove methanol while ethyl acetate is being added back. The volume of this solution of the (2-diisopropylamino)ethyl)benzyl)-p-cresol is adjusted to 700 ml using ethyl acetate and the mixture is heated to 55°C. To form the hydrochloride salt of the (2-diisopropylamino)ethyl)benzyl)-p_x0002_creso

• Therapeutic Function

  Anticholinergic

• Allgemeine Beschreibung

  Tolterodine (Detrol), 2-[3-[bis(1-methylethyl)amino]-1-phenyl-propyl]-4-methyl-phenol, is an antimuscarinicagent that acts on M2 and M3 muscarinic subtypereceptors. By competitively blocking of the muscarinicreceptors results in a reduction of the smooth muscle tone,allowing for greater volume of urine to be stored in the bladder.This results in less urinary incontinence, urgency, andfrequency.

Tolterodine Upstream-Materialien And Downstream Produkte

Tolterodine Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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