289042-12-2

Usage

Uses

Used in Pharmaceutical Industry:
tert-Butyl 6-[(1E)-2-[4-(4-fluorophenyl)-6-(1-methylethyl)-2-[methyl(methylsulfonyl)amino]-5-pyrimidinyl]ethenyl]-2,2-dimethyl-1,3-dioxane-4-acetate is used as an intermediate in the synthesis of Rosuvastatin (R700500), a HMG-CoA reductase inhibitor. Its role in the pharmaceutical industry is crucial for the development and production of Rosuvastatin, which is a widely prescribed medication for lowering cholesterol levels and reducing the risk of cardiovascular diseases.
Chemical Properties:
tert-Butyl 6-[(1E)-2-[4-(4-fluorophenyl)-6-(1-methylethyl)-2-[methyl(methylsulfonyl)amino]-5-pyrimidinyl]ethenyl]-2,2-dimethyl-1,3-dioxane-4-acetate is a white solid, which indicates its stability and suitability for use in various chemical reactions and processes within the pharmaceutical industry. Its specific chemical structure and properties contribute to its role as an intermediate in the synthesis of Rosuvastatin, making it a valuable component in the development of this important medication.

Upstream product

• 894787-92-9 N-(5-bromo-4-(4-fluorophenyl)-6-isopropylpyriinidin-2-yl)-N-methylmethanesulfonamide 
• 153968-96-8 tert-butyl 2-((4R,6S)-2,2-dimethyl-6-vinyl-1,3-dioxan-4-yl)acetate 
• 289042-10-0 N-(5-((diphenylphosphoryl)methyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide 
• 124752-23-4 tert-butyl 2-[(4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate 
• 1207460-27-2 tert-butyl 2-((4R,6S)-6-((E)-2-(4-(4'-fluorophenyl)-6-isopropyl-2-(methylamino)pyrimidin-5-yl)vinyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate 
• 124-63-0 methanesulfonyl chloride 
• 147118-36-3 N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide 
• 799842-07-2 N-[5-(bromomethyl)-4-(4-fluorophenyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide 
• 956034-90-5 N-((5-(1H-benzo[d]imidazol-2-ylthio)methyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methyimethanesulfonamide 
• 1344117-75-4 N-[4-(4-fluorophenyl)-5-{[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl}-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide 
• 1344117-76-5 [4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-(propan-2-yl)pyrimidin-5-yl]methyl diphenyl phosphate 
• 1344117-77-6 N-[4-(4-fluorophenyl)-5-{[(5-methyl-1,3,4-thiadiazol-2-yl)sulfonyl]methyl}-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethane sulfonamide 
• 407577-54-2 tert-butyl 2,4-dideoxy-3,5-O-(1-methylethylidene)-D-erytro-hexonate 
• 953776-62-0 N-(4-(4-fluorophenyl)-6-isopropyl-5-methylpyrimidin-2-yl)-N-methylmethanesulfonamide 

Downstream Products

• 355805-96-8 rosuvastatin methylamine salt 
• 894787-93-0 {(4R,6S)-6-[(E)-2-{4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl}vinyl]-2,2-dimethyl-1,3-dioxan-4-yl}acetic acid 
• 1207460-30-7 [(4R,6S)-6-{(E)-2-[4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-(propan-2-yl)pyrimidin-5-yl]ethenyl}-2,2-dimethyl-1,3-dioxan-4-yl]acetate 1,1-dimethylethylammonium 
• 851440-19-2 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 methyl ester 
• 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 
• 1374771-99-9 rosuvastatin arginine salt 
• 1374771-97-7 (3R,55,6E)-7-[4-(4-fluorophenyl)-2-(N-(methyl)methanesulfonamide)-6-(propan-2-yl)pyrimidin-5-yl]-3,5-dihydroxyhept-6-enoic acid lysine salt 
• 1714147-49-5 C₂₉H₄₂FN₃O₇S 
• 1422619-13-3 7-[4-(4-fluorophenyl)-6-isopropyl-2(N-methyl-N-methanesulfonamido)pyrimidin-5-yl]-(3R)-3-hydroxy-5-carbonyl-6-(E)-heptenoic acid 
• 1094100-06-7 (E)-(3R,5R)-7-[4-(4-fluoro-phenyl)-6-isopropyl-2-(methanesulfonyl-methyl-amino)-pyrimidin-5-yl]-3,5-dihydroxy-hept-6-enoic acid 
• 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 
• 1379688-00-2 rosuvastatin ethanolamine 

Relevant academic research and scientific papers

Rosuvastatin calcium intermediate compound

The invention belongs to the field of organic chemistry, and discloses a rosuvastatin calcium intermediate compound, a synthesis method thereof and application thereof in preparation of rosuvastatin calcium. The preparation method of the rosuvastatin calcium intermediate compound comprises the following specific steps: (1) reacting a compound III with 5-mercapto-1-phenyltetrazole under the actionof an organic alkali to obtain a compound II; (2) reacting the compound II with an oxidant to obtain a compound I crude product. The prepared rosuvastatin calcium intermediate compound I is novel in structure, short in synthesis route, mild in reaction conditions, high in yield and convenient in after-treatment. The compound I reacts with a rosuvastatin side chain, the reaction conditions are mild, the yield and purity of the product are high, and the method has a good industrial prospect.

Preparation method of rosuvastatin calcium

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a preparation method of rosuvastatin calcium. The preparation method comprises steps: in an inert atmosphere protection environment, a specific compound is used as a raw material and is reacted under the action of a dilute acid reagent to obtain a hydroxyl protecting group-removed compound; esterolysisis carried out under the action of an alkaline reagent to obtain rosuvastatin sodium; and concentrating is carried out, a proper amount of water is added, the pH value is adjusted to 3-4 by using anacid, extracting is carried out, an obtained organic layer is cooled and crystallized to obtain a rosuvastatin white solid, the white solid is dissolved in pure water, the pH value is adjusted to 8-9by using an alkali, and reacting with a calcium salt aqueous solution is carried out to obtain rosuvastatin calcium with the purity of 99.5% or above and the impurity content of less than 0.1%.

Rosuvastatin calcium impurity and method for controlling quality of rosuvastatin calcium

The invention provides a rosuvastatin calcium unknown impurity and a preparation method thereof, and further provides a method for controlling the content of the rosuvastatin calcium impurity. According to the method for controlling the content of the rosuvastatin calcium impurity, the content of the impurity is controlled by controlling the content of a compound shown in formula (RC) in an R1 compound. The invention further provides a method for controlling the quality of rosuvastatin calcium by controlling the content of the rosuvastatin calcium impurity.

Preparation method of statins intermediate

The invention discloses a preparation method of a statins intermediate, comprising the following steps: a phosphate compound and an aldehyde compound are subjected to a condensation reaction under theaction of a catalyst and alkali; after the reaction, post-treatment is conducted to obtain the statins intermediate. The statins intermediate includes a rosuvastatin intermediate (Compound A) and a pitavastatin calcium intermediate (Compound B). The preparation method has the advantages of low cost, simple operation and good yield, is environmentally friendly, and is suitable for industrial production.

INTERMEDIATE COMPOUND FOR PREPARING ROSUVASTATIN CALCIUM AND METHOD FOR PREPARING ROSUVASTATIN CALCIUM THEREFROM

Provided are an intermediate compound for preparing rosuvastatin calcium and a preparation method of the rosuvastatin calcium. The method comprises: using the foregoing intermediate compound as a raw material, and subjecting the raw material to a step of Wittig reaction, a step of protecting group removal and hydrolysis and a step of calcium salt formation, so as to obtain the rosuvastatin calcium. The product, which is prepared from the intermediate compound, can be substantially enhanced in stereoselectivity and also notably improved in purity and yield; in addition, the method for preparing rosuvastatin calcium from the intermediate compound is simple, convenient and low in cost.

Purification method of rosuvastatin calcium intermediate

The invention discloses a purification method of a rosuvastatin calcium intermediate shown as Formula (III) as shown in the specification. The purification method is characterized by comprising the steps of heating and mixing a crude product of the rosuvastatin calcium intermediate shown as Formula (III) and a mixed solution of normal hexane and absolute ethyl alcohol till complete dissolution, and then performing cooling and crystallization. According to the method, the mixed solution of absolute ethyl alcohol and normal hexane serves as a recrystallization solvent for purification of the crude product of the rosuvastatin calcium intermediate shown as Formula (III); the purity of the rosuvastatin calcium intermediate shown as Formula (III) in a prepared product is greater than 99%; the maximum purity is 99.8%; the minimum purity is 99.3%; an effect of removing a cis-isomer is obvious; a cis-isomer content is less than 0.1%; and the purification selectivity is high.

A statin intermediate and its derivatives

The invention discloses a preparation method of a statin intermediate and derivatives thereof. The preparation method comprises the steps of: preparing to obtain a compound in a formula (II) through oxidation reaction among a compound in a formula IV, DMSO (dimethylsulphoxide) and alkali in the existence of an alkali metal salt catalyst, and obtaining a compound in a formula (I) by base catalysis through condensation of the compound in the formula (II) and a compound in a formula (III), wherein in the formulas, X is halogens, R is substituted or non-substituted alkyl groups of C1-C6 and alkane cyclic groups or aryl groups of C3-C5, substituent groups of R are the aryl groups, and R1 is selected from one or several of the alkyl groups of C1-C6 and the halogens. Compared with the prior art, the preparation method has the advantages that the compound in the formula IV is not esterified and hydrolyzed for preparing alcohol, then aldehyde (compound in the formula II) is prepared through oxidation, and the compound in the formula II is directly prepared from the compound in the formula IV in one step. The preparation method has the advantages of short steps, simple operation and suitability for industrial production.

A cis rosuvastatin calcium impurity preparation method

The invention discloses a preparation method of a cis-rosuvastatin calcium impurity. According to the preparation method, (4R-cis)-6-carbaldehyde-2,2-dimethyl-1,3-dioxane-4-tert-butyl acetate and [4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesulfonylamino)-5-pyrimidinyl]triphenylphosphonium bromide are used as the raw materials for preparing a target compound by virtue of Witting reaction, isomer separation, deprotection, hydrolysis and salt forming reaction. The method has the characteristics of originality, simplicity in operation, convenience in after-treatment, high product purity and yield and the like. The preparation method has the beneficial effect that certain help is provided for the registration, the declaration, the production and the center control of cis-rosuvastatin calcium as well as the quality improvement of cis-rosuvastatin calcium.

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.