- Synthetic studies on statins. Part 3: A facile synthesis of rosuvastatin calcium through catalytic enantioselective allylation strategy
-
A concise and stereocontrolled synthesis of rosuvastatin calcium has been accomplished, with the key steps including a Keck enantioselective allylation of chloroacetaldehyde with allyltributylstannane to install 5R-stereocenter and a VO(acac)2-catalyzed syn-diastereoselective epoxidation of (S)-1-chloropent-4-en-2-ol to set the requisite 3R-chirality.
- Chen, Xiaofei,Xiong, Fangjun,Zheng, Chen,Li, Jie,Chen, Fener
-
-
Read Online
- Statins intermediate and its derivatives
-
The invention discloses a preparation method for a tatin intermediate and derivatives thereof. The compound adopts a structure shown in a formula I (refer to the specification); the preparation method is that a compound shown in a formula II (refer to the specification) and a nucleophile reagent are subjected to the ring-opening reaction, wherein R is a C1-10 alkoxy group. The preparation method has the advantages that the mild conditions are realized, the reaction operation is simple, the reaction time is short, the product transformation ratio is high and the method is suitable for large-scale production.
- -
-
Paragraph 0022-0023
(2019/04/10)
-
- Preparation process of rosuvastatin calcium preparation
-
The invention provides a preparation process of a rosuvastatin calcium preparation, and belongs to the technical field of pharmaceutical preparations. With (3R)-tert-butyldimethylsiloxy-5-oxy-6-triphenylphosphoranylidene methyl caproate and 4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonyl amino)pyridine-5-formaldehyde as initial raw materials, wittig reaction, deprotection reaction, chiral reduction reaction, hydrolysis reaction and purification are carried out so as to obtain a rosuvastatin calcium crude drug; then the rosuvastatin calcium crude drug is uniformly mixed with a diluent, a disintegrating agent, a stabilizing agent and a lubricant so as to obtain a mixture, and then the mixture is tabletted so as to obtain the rosuvastatin calcium preparation. The preparation process of the rosuvastatin calcium preparation disclosed by the invention has the advantages of simple operation, high yield, low cost and stable quality.
- -
-
-
- Synthetic method for rosuvastatin methyl ester
-
The invention provides a synthetic method for rosuvastatin methyl ester. According to the method, protected butyl ester is used as a raw material and esterified again in presence of a catalyst to prepare rosuvastatin methyl ester. The method is low in cost and high in yield, and a new valuable path is provided for synthesis of rosuvastatin methyl ester.
- -
-
-
- Synthetic method of rosuvastatin
-
The invention provides a synthetic method of rosuvastatin. The method is characterized in that butyl rosuvastatin is esterified in the presence of a neutral titanate catalyst to prepare methyl rosuvastatin. The method has the advantages of low cost and high yield, and provides a new valued approach for synthesis of the methyl rosuvastatin.
- -
-
-
- Method for the preparation of high purity Rosuvastatin Calcium salt
-
The present invention relates to a method for manufacturing a Rosuvastatin calcium salt by using a Rosuvastatin tert-butyl amine salt, and to a method for manufacturing a high purity Rosuvastatin calcium salt, which has impurities less than 0.1% of a diastereomer. The manufacturing method of a high purity Rosuvastatin calcium salt comprises the steps of: 1) manufacturing a compound represented by chemical formula III by reducing a compound represented by chemical formula IV; 2) manufacturing a compound represented by chemical formula II by adding t-butyl amine; and 3) manufacturing a compound represented by chemical formula I by adding a calcium ion to the compound represented by chemical formula II.COPYRIGHT KIPO 2016
- -
-
Paragraph 0038; 0039
(2017/01/17)
-
- 3,5-dihydroxyhept-6-enoic acid derivative preparation method
-
The invention relates to a preparation method of 3, 5-dihydroxy-6-heptenoic acid derivatives. The preparation method comprises the steps of hydrolyzing crude statin ester to form a water-soluble alkali metal salt, extracting by using a solvent to remove impurities which cannot be dissolved into water, and converting at high yield to form ester with relatively high purity; then, purifying the ester by using a recrystallization way to obtain pure statin ester; and finally, converting the pure statin ester at high yield to form statin calcium, namely the 3, 5-dihydroxy-6-heptenoic acid derivatives. The 3, 5-dihydroxy-6-heptenoic acid derivatives, namely rosuvastatin calcium and pitavastatin calcium, synthesized by using the preparation method are high in purity and total yield, relatively low in cost and beneficial to mass production.
- -
-
Paragraph 0047 - 0050
(2017/04/19)
-
- Rosuvastain calcium intermediate crystallization method
-
The invention discloses a crystallization method of a rosuvastatin calcium intermediate. The crystallization method comprises the following steps: (1) adding the prepared grease of an intermediate H3 to a mixed solvent composed of an ester solvent, an alkane solvent and an ether solvent, performing primary pulping and evaporating out one part of the mixed solvent under reduced pressure; (2) adding the ether solvent and performing secondary pulping; (3) adding the alkane solvent; (4) adding the seed crystal of the intermediate H3; and (5) adding the ether solvent, performing third pulping, and separating out solid to obtain the solid product of the intermediate H3. According to the crystallization method of the rosuvastatin calcium intermediate, the mixed solvent is adopted to crystallization step by step so as to guarantee smooth separation of the rosuvastatin calcium intermediate H3 in the solid form and the obtained intermediate H3 is high in purity; and meanwhile, the operating method is simple, good in repeatability and suitable for industrial production.
- -
-
Paragraph 0037; 0038
(2020/03/23)
-
- PROCESS FOR PREPARING ROSUVASTATIN CALCIUM THROUGH NOVEL AMINE SALT
-
The present invention provides a process for preparing pure rosuvastatin of formula I, or pharmaceutically acceptable salts thereof through rosuvastatin l-(l-naphthyl)ethyl salt of formula II wherein wavy line (>~w) represent (R), (S) stereochemistry or racemate thereof.
- -
-
-
- PROCESS FOR THE PREPARATION OF ROSUVASTATIN CALCIUM VIA NOVEL AMINE INTERMEDIATE
-
The present invention, relates to novel amine salts of rosuvastatin and its process for the preparation. Moreover, the present invention also relates to improved process for the preparation of rosuvastatin calcium, employing novel amine salts as an intermediate.
- -
-
-
- STATIN DERIVATIVES
-
Dinitrate statins having improved pharmacological activity are described. They can be employed for treating and/or preventing several diseases, in particular acute coronary syndromes, neurodegenerative disorders as well as for reducing cholesterol levels.
- -
-
Page/Page column 59
(2012/01/13)
-
- PREPARATION METHOD OF ROSUVASTATIN CALCIUM AND ITS INTERMEDIATES
-
.A preparation method of rosuvastatin calcium (Formula 1), which can be used for the production of medicament lowering the levels of LDL-cholesterol and triglycerides in vivo, is provided. Such preparation method is suitable for industrial production. Furthermore, the intermediate crystallines used in the preparation method are provided.
- -
-
-
- PROCESS FOR THE PREPARATION OF ROSUVASTATIN
-
The invention relates to a process for the preparation of a HMG - CoA reductase inhibitor such as rosuvastatin, as well as intermediates useful in such process. The invention also relates to salts of HMG-CoA reductase inhibitors and processes for preparing same as well as processes for preparing pharmaceutically acceptable salts of HMG-CoA reductase inhibitors.
- -
-
Page/Page column 41
(2010/08/08)
-
- AN IMPROVED PROCESS FOR THE PREPARATION OF ROSUVASTATIN CALCIUM
-
The present invention provides an improved process for the preparation of amorphous Rosuvastatin Calcium through novel amine salts of Rosuvastatin.
- -
-
Page/Page column 8-9
(2010/04/27)
-
- CRYSTALLINE FORM OF(7-[4-(4-FLUOROPHENYL)-6-ISOPROPYL-2-(N- METHYL-N-METHYLSULFONYLAMINO)PYRIMIDIN-5-YL]-(3R,5S)- DIHYDROXY-(E)-6-HEPTENOIC ACID INTERMEDIATE, PROCESS FOR PREPARING THE SAME AND USE THEREOF
-
Disclosed herein is a crystalline form of methyl 7-[4-(4-flourophenyl)-6- isopropyl-2-(N-methyl-N-methylsulfonylamino)-pyrimidin-5-yl]-(3R)-3-hydroxy-5-oxo- (E)-6-heptenate (rosuvastatin intermediate), process for producing the same and using the same for producing rosuvastatin or pharmaceutically acceptable salts thereof.
- -
-
Page/Page column 9
(2009/12/02)
-
- PROCESS FOR PREPARATION OF CALCIUM SALT OF ROSUVASTATIN
-
The invention relates to commercially viable process for the preparation of Rosuvastatin by an early introduction of correct absolute stereochemistry at C-5 (S) of Rosuvastatin side chain followed by regioselective chain extension using novel side chain building blocks and less expensive reagents. It is yet another object of the invention is to provide novel intermediates that may be used for the preparation of Calcium salt of Rosuvastatin.Formula (I).
- -
-
Page/Page column 15; 16
(2010/11/24)
-
- A PROCESS FOR THE PREPARATION OF ROSUVASTATIN INVOLVING A TEMPO-MEDIATED OXIDATION STEP
-
The present invention provides a process for the preparation of the rosuvastatin intermediate FPP-CHO and its conversion to rosuvastatin and pharmaceutically acceptable salts thereof.
- -
-
Page/Page column 16
(2010/10/20)
-
- PROCESS FOR THE PREPARATION OF ROSUVASTATIN
-
The present invention relates to a cost effective and industrially advantageous process for the preparation of 4-4(fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulphonylamino)-5-pyrimidinecarboxaldehyde, referred to here as pyrimidine aldehyde of structural Formula I and to the use of this compound as intermediate for the preparation of rosuvastatin.
- -
-
Page/Page column 8; 13
(2008/06/13)
-
- Synthesis and biological activity of methanesulfonamide pyrimidine- and N-methanesulfonyl pyrrole-substituted 3,5-dihydroxy-6-heptenoates, a novel series of HMG-CoA reductase inhibitors
-
A novel series of methanesulfonamide pyrimidine- and N-methanesulfonyl pyrrole-substituted 3,5-dihydroxy-6-heptenoates were synthesized and evaluated for their ability to inhibit the enzyme HMG-CoA reductase in vitro. Monocalcium bis(+)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N- methanesulfonylaminopyrimidin)-5-yl]-(3R,5S)-dihydroxy- (E)-6-heptenoate (3a, S-4522) was selected as a candidate for further evaluation. Compound 3a was approximately four times more potent than lovastatin sodium salt (in inhibiting HMG-CoA reductase in vitro (IC50 = 11 nM). Compound 3a was shown to be the most potent cholesterol biosynthesis inhibitor in this series (IC50 = 1.12 nM) in rat isolated hepatocytes; its inhibitory activity was approximately 100 times more potent than pravastatin.
- Watanabe, Masamichi,Koike, Haruo,Ishiba, Teruyuki,Okada, Tetsuo,Seo, Shujiro,Hirai, Kentaro
-
p. 437 - 444
(2007/10/03)
-