Lek Pharmaceuticals D.d.

Other

Ljubomir Antoncic

Anton Copar

Gorazd Sorsak

Zoran Ham

Breda Husu-Kovacevic

Matej Antoncic

Peter Svete

Boris Marolt

Breda Husu-Kovacecic

A process for the preparation of amorphous atorvastatin calcium. The process includes providing a reaction mixture having a pH between 6.5 and 8.0 containing a sodium salt of atorvastatin and tetrahydrofuran. A non-cyclic chlorinated organic solvent selected from the group consisting of dichloromethane, trichloroethane, tetrachloroethane and chloroform or addition of cyclic hydrocarbon solvent selected from the group consisting of cyclohexane, cyclopentane and methyl cyclohexane is added to provide a mixture of organic solvents. An equivalent or an excess quantity of a source of calcium ions selected from the group consisting of calcium acetate and calcium chloride is added. Amorphous atorvastatin calcium is isolated from an organic phase comprising the mixture of organic solvents.

Process for the preparation of amorphous calcium salt of atorvastatin

Present invention refers to the process of preparing amorphous atorvastatin calcium without intermediate isolation of crystal or undefined mixture of crystal and amorphous atorvastatin calcium, respectively. Forming of calcium atorvastatin salt is carried out in a mixture of chlorinated organic solvent or cyclic hydrocarbon solvent, respectively, the non-hydroxylic organic solvent, and water, the source of calcium ions is calcium acetate or calcium chloride, respectively.

4-bromomethyl-2'-formylbiphenyl and 4-bromomethyl-2&#x2032;-hydroxymethylbiphenyl are useful starting material for the preparation various angiotenzin II antagonists, which are prepared from 4-bromomethyl-2&#x2032;-cyanobiphenyl or 4&#x2032;-bromomethylbiphenylcarboxyilic derivatives using selected hydride reagent.

Synthesis of 4-bromomethyl-2'-formylbiphenyl and 4-bromomethyl-2&#x2032;-hydroxymethylbiphenyl and its use in preparation of angiotensin II antagonists

The invention relates to a process of preparing amorphous (4R-cis)-6-[2-[3-phenyl-4-(phenylcarbamoyl)-2-(4-fluorophenyl)-5-(1-methylethyl)-pyrrol-1-yl]-ethyl]-2,2-dimethyl-[1,3]-dioxane-4-yl-acetic acid-tertiary butyl ester which is a useful pharmaceutical intermediate in the preparation of atorvastatin salts.

Process for preparing amorphous (4R-cis)-6-[2-[3-phenyl-4-(phenylcarbamoyl)-2-(4-fluorophenyl)-5-(1-methylethyl)-pyrrol-1-yl]-ethyl]-2,2-dimethyl-[1,3]-dioxane-4-yl-acetic acid

Pharmaceutically suitable crystalline and amorphous alkali and earth-alkali salts of 2-n-butyl-4-chloro-5-hidrox-ymethyl-1-[[2'-(1 H-tetrazole-5-yl)[1.1&#x2032;-biphenyl]-4-yl]-1 Himidazole have been prepared and new manufacturing, purification and isolation procedure for said salts in high purity have been described. Stable pharmaceutical compositions containing new crystalline potassium salts of 2-n-butyl-5-chloro-5hidroxymethyl-1-[[2&#x2032;-(1H-tetrazole-5-yl)[1.1&#x2032;-biphenyl]-44-yl]-1H-imidazole have been prepared.

Growing community of inventors

Ljubljana, Slovenia

Ljubomir Antoncic