Lek Pharmaceuticals D.d.

Zlicar, Marko

Marko Zlicar

Zdenko Casar

Damjan Sterk

Rudolf Rucman

Matjaz Ustar

A pure amorphous form of rosuvastatin calcium substantially free from alkali metal impurities is disclosed. A process of preparing a pure amorphous form of rosuvastatin calcium is disclosed, which comprises hydrolysis of C-Calkyl esters of rosuvastatin, preferably tert-butyl ester of rosuvastatin, with an organic nitrogen base, e.g. guanidines, amidines, amines and quaternary ammonium hydroxides, in the presence of water, optionally containing aprotic solvent, following the conversion of thus obtained rosuvastatin salt with a source of calcium to obtain rosuvastatin calcium, which is then isolated. An alternative process is disclosed, which comprises the conversion of numerous novel ammonium salts of rosuvastatin, preferably tert-octylammonium salt of rosuvastatin, with the source of calcium to desired commercial rosuvastatin calcium. Rosuvastatin calcium is an inhibitor of HMG CoA reductase, useful in the treatment of hyperlipidemia, hypercholesterolemia and atherosclerosis.

Process for preparing amorphous rosuvastatin calcium of impurities

The present invention relates to process to prepare &#x3b2;-aminobutyryl compounds having &#x3b2;-amino acid core structural moieties and optionally having &#x3b3;-phenyl and/or heterocyclic structural moieties. Such compounds are useful as key structure framework of modern drug chemistry.

Methods of synthesis of &#x3b2;-aminobutyryl substituted compounds

Present invention represents process for the preparation of HMG-CoA reductase inhibitors, in particular rosuvastatin calcium introducing L-malic acid as the source of chirality for the side chain.

Process for the synthesis of rosuvastatin calcium

A new process for preparing pure amorphous rosuvastatin calcium, substantially free of impurities, is disclosed. A process comprising hydrolysing a Cto Calkyl ester of rosuvastatin, preferably methyl rosuvastatin or tert-butyl rosuvastatin, with a base, e.g. sodium hydroxide, in the presence of an aprotic solvent, preferably tetrahydrofuran and N,N-dimethyl acetamide, or in the presence of a mixture of an aprotic solvent and water, to obtain a solution of rosuvastatin salt, which may be converted to another rosuvastatin salt using another cation, e.g. with calcium cation to obtain rosuvastatin calcium. Rosuvastatin amine salts may be obtained as well. In another preferred aspect of the invention rosuvastatin free acid may be converted to various rosuvastatin salts, e.g. to rosuvastatin calcium, rosuvastatin sodium or various rosuvastatin amine salts, including rosuvastatin solvates, e.g. rosuvastatin calcium hydrate. Rosuvastatin calcium is useful in the treatment of hyperlipidemia, hypercholesterolemia and atherosclerosis.

Process for preparing pure amorphous rosuvastatin calcuim

This invention relates to a novel method for the removal of a silyl protecting group from the 4-hydroxy group of tetrahydropyran-2-ones, which method is particularly suitable in the process for the preparation of simvastatin and derivatives and analogs thereof.

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Celje, Slovenia

Marko Zlicar