Troxypyrrolium tosilate

Xylamidine tosylate,Wellcome Research Laboratories

Serotonin inhibitor.

A mixture of 3-methylphenylacetonitrile and dry ethanol was cooled in an ice- bath and dry hydrogen chloride was passed. The mixture was allowed to stand at room temperature for 3 days and then treated portionwise, with vigorous shaking and occasional cooling, with a saturated solution of ammonia in dry ethanol. Addition was continued until a smell of ammonia persisted. The mixture was allowed to stand at room temperature for 2 days and then filtered. The fitltrate was treated with a saturated aqueous solution of 1.1 equivalents of sodium p-toluene-sulfonate and diluted with water. The crystalline precipitate was removed and 3-methylphenylacetamidine p- toluenesulphonate (recrystallised from ethanol) was obtained.
A mixture of methyl phenolate and anhydrous potassium carbonate in dry ethyl methyl ketone was stirred and heated to reflux, during the dropwise addition of a solution of 2-chloropropionitrile in dry ethyl methyl ketone containing finely-powdered potassium iodide. The addition took 20 min. Stirring and heating were continued for a total of 2 h after which the mixture was cooled, poured into water and extracted with ether. The combined ether extract was washed several times with 2 N sodium hydroxide to remove phenol, dried over anhydrous sodium sulfate, and evaporated. The residue was distilled under water-pump vacuum to give pure 2-(3-methoxy-phenoxy)- propionitrile, boiling point 152-154°C/13 mm.
A solution of 2-(3-methoxy-phenoxy)-propionitrile in dry ether was added dropwise to a stirred suspension of lithium aluminium hydride in dry ether. The mixture was then heated to reflux for 3 h, cooled and treated cautiously (vigorous stirring) with water, then with 15% aqueous sodium hydroxide and finally with water. The mixture was stirred for 20 min and filtered. The filtrate was dried over anhydrous potassium carbonate and evaporated. The residue was distilled under water-pump vacuum to give pure 2-(3-methoxy-phenoxy)- propylamine, boiling point 148-152°C/13 mm.
2-(3-Methoxy-phenoxy)-propylamine was added to a suspension of 3- methylphenylacetamidine ρ-toluenesulphonate in absolute ethanol. The mixture was heated to reflux for 4 h by which time the initially vigorous evolution or ammonia had practically ceased. The resulting solution was cooled somewhat and diluted with ether to give an oil which rapidly crystallised on scratching. The solid was filtered and recrystallised from a mixture of ethanol and water to give N-[2-(3-methoxyphenoxy)-propyl]-3- methylbenzeneethanimidamide ρ-toluenesulphonate, melting point 93-96°C (crystallized from water).

Serotonin antagonist, Nootropic