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AssigneeZaklady Farmaceutyczne Polpharma S.A.
InventorsRoman Szramka, Jerzy Drygas, Marcin Szulc, Robert Rynkiewicz
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The method of synthesizing vardenafil base, in anhydrous conditions, by chlorosulfonation of 2-(2-etoxy-phenyl)-5 -methyl-7-propyl-iH-imidazo[5,1-fJ[1,2,4]triazin-4-one in a mixture of thionyl chloride and sulfurochloridic acid followed by amidation of the product, 4-etoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)benzene-sulfonic acid chloride with N-ethylpiperazine, in an aprotic solvent, in the presence of an inorganic base and the method of conversion the product, vardenafil base, to yield vardenafil monohydrochloride trihydrate having a melting point of 234° C. by contacting with water of the anhydrous modification V of vardenafil monohydrochloride in an organic solvent. The subject of the invention is also the anhydrous modification V of vardenafil monohydrochloride and its use in the preparation of vardenafil monohydrochloride trihydrate having a melting point of 234° C.
A method for manufacturing vardenafil and/or its salts, comprising chlorosulfonating 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one in thionyl chloride mixed with sulfurochloridic acid under reflux at the solvent boiling point, isolating the synthesized 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)benzene-sulfonic acid chloride from the reaction mixture under anhydrous conditions, amidating the 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)benzene-sulfonic acid chloride with N-ethylpiperazine in an aprotic solvent in the presence of an inorganic base, and after completion of the reaction, isolating the prepared vardenafil base and optionally transforming the vardenafil base into a salt.
A method for manufacturing vardenafil monohydrochloride trihydrate having a melting point of 234° C. comprising:
An anhydrous modification V of vardenafil monohydrochloride in crystalline form characterized on powder diffractogram by the following set of peak positions, described by interplanar distances d (Å) and diffraction angles 2Θ(°):
Dependencies are inferred from the claim text.