Preparation method of rosuvastatin calcium impurity

Abstract

The invention discloses a preparation method of a rosuvastatin calcium impurity. The target compound is produced from 4-(4-fluorophenyl)-6-isopropyl-2(N-methyl-methanesulfonylamino)pyrimidine-5-yl]-formaldehyde and methyl (3R)-3-t-butyldimethylsiloxy-5-carbonyl-6-(triphenylphosphinevinyl)caproate through a Witting reaction, HF deprotection, alkaline hydrolysis and an acidifying reaction. The method has the characteristics of short synthesis route, simple operation, convenient post-treatment, and high purity and high yield of the product. The method provides certain help for register reporting of rosuvastatin calcium, production middle control and improvement of the quality of rosuvastatin calcium.

Description

technical field [0001] The present invention relates to a compound 7-[4-(4-fluorophenyl)-6-isopropyl-2(N-methyl-N-methanesulfonamido)pyrimidin-5-yl]-(3R)- The preparation method of hydroxy-5-carbonyl-6-(E)-heptenoic acid belongs to the technical field of medicine synthesis. Background technique [0002] Rosuvastatin Calcium, chemical name: bis-[7-[4-(4-fluorophenyl)-6-isopropyl-2(N-methyl-N-methanesulfonamido)pyrimidin-5-yl ]-(3R,5S)-3,5-dihydroxyhept-6-(E)-enoic acid] calcium salt (2:1). It is a cardiovascular drug developed by AstraZeneca and first approved for marketing in the Netherlands in November 2002. It was approved by the US FDA in August 2003, and it has been listed in more than 60 countries, and clinical trials have been completed in my country. The trade name is Crestor. The drug has strong HMG-COA reductase inhibitory activity, and its effect of lowering LDL-C and raising HDL-C is superior to other statins on the market, and has good tolerance and safety. S...

AI Technical Summary

Problems solved by technology

[0006] The target product of its preparation is bis-[E-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]-pyrimidin-5-yl] -3R-3-Hydroxy-5-oxo-6-heptenoic acid] calcium salt), the applicant has tried to use the compound (+)-(3R)-7-[4-(4-fluorophenyl) directly -6-Isopropyl-2-[N-methyl-N-(methylsulfonyl)amino]-pyrimidin-5-yl]-3-hydroxy-5-oxo-(6E)-heptenoic acid tert-butyl Esters as substrates for the preparation of 7-[4-(4-fluorophenyl)-6-isopropyl-2(N-methyl-N-methanesulfonamido)pyrimidin-5-yl]-(3R)-hydroxy -5-carbonyl-6-(E)-heptenoic acid, but found during the experiment that the substrate cannot be purchased from the market and needs to be prepared according to the synthesis process reported in the literature, but the synthesis process reported in the literature is very complicated, Including complex and difficult-to-control oxidation reactions, the yield of the substrate is low (only 70% of the yield in the manganese oxide oxidation step), which greatly limits the overall yield

[0007] So far, no researcher has been found about the compound 7-[4-(4-fluorophenyl)-6-isopropyl-2(N-methyl-N-methanesulfonamido)pyrimidin-5-yl]- Report on the preparation method of (3R)-hydroxy-5-carbonyl-6-(E)-heptenoic acid

Images