918544-87-3Relevant academic research and scientific papers
NOVEL CLASS OF COMPOUNDS FOR THE TREATMENT OF CARDIOVASCULAR DISEASE
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, (2017/09/05)
The present invention relates to the field of medicine, specifically the field of treatment and prevention of cardiovascular diseases.
A METHOD FOR THE PRODUCTION OF THE HEMI-CALCIUM SALT OF (E)-7-[4-(4-FLUOROPHENYL)-6-ISOPROPYL-2-[METHYL(METHYLSULFONYL)AMINO]PYRIMIDIN-5-YL](3R,5S)-3,5-DIHYDROXYHEPT-6-ENOIC ACID
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Page/Page column 10, (2008/06/13)
A method of producing the hemi-calcium salt of rosuvastatin, i.e. of (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid of formula (I), in the crystalline or amorphous solid state, wherein a) the lactone of formula (IV), or ester or amid of general formulae (V) or (XIII), wherein X is either oxygen or amino group, R1CR2 is a protecting group, wherein R1 and R2 are preferably selected from C1 to C3 alkyls, and R is an alkyl selected from C1 to C10 alkyls, preferably methyl, ethyl or tert-butyl, after removing the protecting group in the case of the compound of formula (V), ia converted, by alkaline hydrolysis with an alkali metal or Ca2+ base, into a salt of rosuvastatin, b) in the case that an alkali metal base was used in step (a), the resulting alkali salt of rosuvastatin is converted into the calcium salt of rosuvastatin by reaction with a calcium salt in aqueous environment, c) crude calcium salt of rosuvastatin of formula (I) is extracted into a solvent partially miscible with water selected from the group including R1COOR2, R1COR2, or R1OH, wherein R1 and R2 independently mean hydrogen or a residue of a C1 to C10 aliphatic hydrocarbon, C6 aromatic hydrocarbon, C5 or C6 cyclic hydrocarbon, or a combination of an aliphatic and aromatic or cyclic hydrocarbon, d) the solution of the calcium salt of rosuvastatin prepared according to step (c) is further washed with water, and e) the product of formula (I) is isolated by cooling the solution and filtration, or by adding an anti-solvent and filtration, or by spraying into the stream of an inert gas.
