Antienite

Originator

Antienite,Onbio Inc.

Manufacturing Process

A mixture of 4 parts of 2-iminothiazoline, 8.3 parts of bromomethyl-2- thienylketone and 40 parts of absolute ethanol is stirred and refluxed for 2 hours in a water-bath. After cooling, the precipitated hydrobromide is filtered off. From this salt the free base is liberated on treating with ammonium hydroxide solution and it is extracted with chloroform. The organic extract is separated, treated with activated charcoal, filtered and the filtrate is first dried over magnesium sulfate and then evaporated. The solid residue is recrystallized from 24 parts 2-propanol, to yield 2-imino-3-[(2- thienylearbonyl)-methyl]-thiazoline; MP: 117.5°-118.5°C.
A mixture of 4 parts of 2-imino-3-[(2-thienylcarbonyl)methyl]thiazoline, 50 parts of acetic anhydride and 1.15 parts of sodium acetate is stirred and refluxed for 15 minutes. The formed sodium bromide is filtered off. From the filtrate, the excess of acetic anhydride is distilled and the residual solid is recrystallized from 2-propanol. The solid is filtered off and dried in vacuum, yielding 2-(acetylimino)-3-[(2-thienylcarbonyl)methyl]thiazoline; MP: 146°- 147.5°C.
To a stirred mixture of 13 parts of 2-(acetylimino)-3-(2- thienylcarbonyl)methyl]thiazoline hydrobromide and 64 parts of ethanol are added portion wise 3 parts of sodium borohydride (exothermic reaction). After the addition is complete, the whole is stirred and refluxed for one hour. The solvent is evaporated. The solid residue is dissolved in hydrochloric acid 4 N. After keeping at room temperature, it crystallizes again. The solid is filtered off and dissolved in water. The aqueous solution is rendered alkaline with ammonium hydroxide and extracted with chloroform. The chloroform extract is dried over magnesium sulfate and evaporated. The solid residue is recrystallized twice: first from 4-methyl-2-pentanone and once more from 400 parts of water. After drying in vacuum, DLl-2-(acetylimino)-3-[2-hydroxy-2-(2- thienyl)ethyl]thiazoline is obtained; MP: 132.5°-133°C.
A solution of 2 parts of DL-2-(acetylimino)-3-[2-hydroxy-2-(2- thienyl)ethyl]thiazoline in 16 parts of thionylchloride and 45 parts chloroform is stirred and refluxed for one hour. After cooling the whole is extracted with water. The acid aqueous solution is separated, washed with toluene, alkalized with ammonium hydroxide solution and extracted with chloroform. The extract is dried over magnesium sulfate and evaporated. The oily residue is dissolved in 40 parts boiling 2-propanol. To this warm solution is added a warm solution of an equivalent quantity of oxalic acid dihydrate in 2-propanoL After cooling to room temperature, the precipitated oxalate is filtered off and dried in vacuum, yielding DL-5,6-dihydro-6-(2-thienyl)imidazo[2,1-b]thiazole oxalate; MP: 192°-193°C.
A mixture of 6 parts DL-2-(acetylimno)-3-[2-hydroxy-2-(2- thienyl)ethyl]thiazoline and 80 parts phosphoroxy-chloride is heated in a water-bath for 2 hours at a temperature of 100°C. On cooling, the reaction mixture is poured into water. The whole is alkalized with ammonium hydroxide solution and extracted with toluene. The extract is dried over magnesium sulfate and evaporated in vacuum. The oily residue is dissolved in 40 parts boiling 2-propanol. To this warm solution is added a warm solution of an equivalent quantity of oxalic acid dihydrate in 2-propanol. After cooling to room temperature, the precipitated salt is filtered off and dried in vacuum, yielding DL-5,6-dihydro-6-(2-thienyl)imidazo[2,1-b]thiazole oxalate; MP: 193°-194°C.
An aqueous solution of this salt is alkalized with ammonium hydroxide and extracted with toluene. The extract is dried over magnesium sulfate and evaporated. The oily residue is crystallized from 12 parts xylene. The solid is filtered off and dried in vacuum, yielding DLl-5,6-dihydro-6-(2- thienyl)imidazo[2,1-b]thiazole; MP: 58°-62°C.
To a solution of 1.2 parts of DL-5,6-dihydro-6-(2-thienyl)imidazo[2,1- b]thiazole in 24 parts acetone is added a slight excess of a solution of hydrogen chloride in 2-propanol. The oily precipitate solidifies on seeding with the solid hydrochloride salt and scratching. The salt is filtered off and dried, to yield DL-5,6-dihydro-6-(2-thienyl)imidazo[2,1-b]thiazole hydrochloride; M.P. 159°-160.5°C.

Therapeutic Function

Anthelmintic