Rosuvastatin is an active pharmaceutical ingredient (API) having the chemical name (E)-(3R,5S)-7-[4-(4-Fluorophenyl)-6-isopropyl-2-[(methylsulfonyl)(methyl)amino]pyrimidin-5-yl]-3,5-dihydroxyhept-6-enoic acid and having structural formula (I):

Rosuvastatin and other APIs belonging to the same family of statins, are characterized by the presence of two oxydrilic groups bound to asymmetric carbon atoms which are part of a side chain linked to a pyrimidine ring. Rosuvastatin is currently marketed as a calcium salt (Rosuvastatin calcium), or as a hemicalcium salt of formula (II):
having the chemical name 6-Heptenoic acid, 7-[4-(4-fluorophenyl)-6-(1-methylethyl)-2-[methyl (methylsulfonyl)amino]-5-pyrimidinyl]-3,5-dihydroxy-, calcium salt (2:1), (3R,5S,6E)- and with commercial names such as Crestor®, Fortius®, Rostar® and Rozavel®.
Rosuvastatin is an inhibitor of 3-Hydroxy-3-Methylglutaryl-Coenzime A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to Mevalonate, a limiting agent of the biosynthesis of Cholesterol and it is therefore used to treat and prevent hypercholesterolemia, to promote the regression of atherosclerotic plaque and to prevent cardiovascular events.
Several methods for the synthesis of this API are disclosed in the literature. Such methods are described, for example, in EP0521471A1, in particular in Example 1, and more recently in WO2009/128091 and WO2009/118598. Several such methods are directed to improving the quality of the product by means of the purification of a relatively early intermediate in the form of Rosuvastatin methyl or ethyl ester. However, this intermediate, to be converted to Rosuvastatin, must be hydrolized and thus during this step Rosuvstatin may racemize, thereby decreasing the optical purity of the final compound.
USPTO Backgrounds
USPTO Backgrounds