851440-19-2

Basic information

• Product Name: (Intermediates of Rosuvastatin Calcium R-4
• Synonyms: (Intermediates of Rosuvastatin Calcium R-4
• CAS NO: 851440-19-2
• Molecular Weight: 535.637
• Mol File: 851440-19-2.mol

Chemical Properties

• CAS DataBase Reference: (Intermediates of Rosuvastatin Calcium R-4(CAS DataBase Reference)
• NIST Chemistry Reference: (Intermediates of Rosuvastatin Calcium R-4(851440-19-2)
• EPA Substance Registry System: (Intermediates of Rosuvastatin Calcium R-4(851440-19-2)

Safety Data

• Hazardous Substances Data: 851440-19-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Intermediates of Rosuvastatin Calcium R-4 are used as essential building blocks for the synthesis of rosuvastatin calcium, a widely prescribed medication for the treatment of high cholesterol and related conditions. They undergo precise reactions and purification steps to create the final active ingredient of the medication, ensuring its quality and purity for pharmaceutical formulations.
Used in Cholesterol-Lowering Medications:
Intermediates of Rosuvastatin Calcium R-4 are used as key components in the development of cholesterol-lowering medications, specifically rosuvastatin calcium. They contribute to the overall effectiveness of the medication in reducing high cholesterol levels and managing related health conditions.

Upstream product

• 67-64-1 acetone 
• 147118-40-9 (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid methyl ester 
• 1388627-65-3 2-((4R,6S)-6-((benzo[d]thiazol-2-ylsulfonyl)methyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetic acid methyl ester 
• 147118-37-4 N-[4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide 
• 77-76-9 2,2-dimethoxy-propane 
• 391218-16-9 2-((4R,6S)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetic acid methyl ester 
• 1388624-32-5 2-((4R,6S)-6-((1-methyl-1H-tetrazol-5-ylsulfonyl)methyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate methyl ester 
• 1388624-31-4 2-((4R,6S)-2,2-dimethyl-6-((1-methyl-1H-tetrazol-5-ylthio)methyl)-1,3-dioxan-4-yl)acetic acid methyl ester 
• 171523-71-0 (+)-(3R,5S)-Methyl 6-acetoxy-3,5-(isopropylidenedioxy)hexanoate 
• 164576-45-8 (4R-cis)-6-formyl-2,2-dimethyl-1,3-dioxane-4-acetic acid methyl ester 
• 140164-51-8 methyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-1,3-dioxane-4-yl)acetate 
• 67-56-1 methanol 
• 289042-12-2 2-[(4R,6S)-6-[(E)-2-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamido)-6-(isopropyl)pyrimidin-5-yl]vinyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetic acid tert butyl ester 
• 124752-23-4 tert-butyl 2-[(4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate 

Downstream Products

• 918544-87-3 (3R,5S,E)-7-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidin-5-yl)-3,5-dihydroxy-N-methylhept-6-enamide 
• 503610-43-3 Rosuvastatin lactone 
• 917805-74-4 (3R,5S,6E)-7-[4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-(propan-2-yl)pyrimidin-5-yl]-3,5-dihydroxyhept-6-enoic acid-2-methylpropan-2-amine 
• 147118-40-9 (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid methyl ester 
• 917805-79-9 rosuvastatin tetramethyl ammonium salt 

Relevant articles and documents

Synthesis of rosuvastatin intermediate synthesis process

The present invention discloses a synthesis process of (4R,6S,E)-2-{6-[2-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl (methylsulfonyl) amino) pyrimidin-5-yl] ethenyl]-2,2-dimethyl-1,3-epoxyhexane-4-yl} acetate alkyl ester. With an aprotic polar solvent as solvent, 4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesulfonyl amino)-5-pyrimidine methyl, n-butyl lithium, 2,2,6,6-tetramethyl piperidine or LDA react with trimethyl silicon chloride; and then the reaction products react with (4R-cis)-6-[(acetyloxy) methyl]-2,2-dimethyl-1,3-dioxo hexane-4-alkyl acetate under catalysis of cesium fluoride in an aprotic polar solvent to produce the target product. The process uses trimethyl silicon as a condensation agent, and does not use alkali; the cesium fluoride is directly used as a catalyst; and the usage amount and three wastes are less. Z type condensation ethylenic bond is less than 10%, which is much less than the triphenylphosphine process. The reaction process does not need low temperature, is easy to realize industrialization and has the advantages of easily available raw materials and low cost.

Rosuvastatin intermediate compound and preparation method and application thereof

The invention relates to an intermediate compound for preparation of rosuvastatin calcium. A structure of the intermediate compound is shown as a formula (I), and the intermediate compound is stable and high in nucleophilicity and reaction activity. In addition, the invention further relates to a preparation process suitable for industrial production of rosuvastatin calcium. Due to adoption of the intermediate compound, a rosuvastatin calcium preparation method is mild in reaction condition, free of ultralow-temperature equipment, simple in aftertreatment and easy in operation, and intermediate product olefin which is an intermediate compound shown as a formula (III) is high in stereoselectivity and yield, high in product quality and high in economic benefit.

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.

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.

PROCESS FOR THE PREPARATION OF A THIOPRECURSOR FOR STATINS

The present invention relates to a process for the preparation of a precursor for the synthesis of hexanoic acid derived statins and to the use of said precursor in the manufacture of a medicament.

METHYLTETRAZOLE SULFIDES AND SULFONES

The present invention relates to a process for the preparation of a 1-methyl-1H-tetrazole-5-thio derivative comprising reaction of a halomethyl substrate with 1-methyl-H-tetrazole-5-thiol to obtain a thio-ether compound, and oxidizing the thio-ether compound to the corresponding sulfone. In case of a chiral halomethyl substrate, the resulting chiral diol sulfone derivative is suitable as a building block for statin type compounds.

PROCESS FOR THE PREPARATION OF DIOL SULFONES

The present invention relates to a process for the preparation of a diol sulfone derivative comprising reaction of a halomethyl substrate with a thio-aryl compound to obtain a thio-ether compound, and oxidizing the thio-ether compound to the corresponding sulfone. In case of a chiral halomethyl substrate, the resulting chiral diol sulfone derivative is suitable as a building block for statin type compounds.

PROCESS FOR THE PREPARATION OF ROSUVASTATIN AND INTERMEDIATES

The subject of the present invention is a process for the preparation of rosuvastatin by reacting a compound of formula II, by alkalic hydrolysis to give a compound of formula III, thereafter reacting with an organic or inorganic base to form a salt, eliminating the acetonide group and reacting with calcium-chloride in a base. A further subject of the present invention is a compound of formula III and its salts formed by organic or inorganic base.

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

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.