cas 289042-12-2, 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

Articles about 289042-12-2Total 30 be found

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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.
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(2020/10/14)

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%.
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Paragraph 0028-0031

(2020/06/17)

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.
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Paragraph 0067-0068; 0076-0077

(2019/06/30)

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.
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Paragraph 0052-0055; 0062-0065; 0072-0075; 0082-0085

(2018/11/27)

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.
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Paragraph 0045; 0046

(2017/08/25)

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.
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Paragraph 0030; 0034; 0035; 0042; 0043

(2017/10/13)

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.
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Paragraph 0045; 0046; 0051; 0052

(2017/11/27)

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.
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Paragraph 0049; 0050

(2017/08/29)

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.
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Paragraph 0046-0047

(2017/02/24)

A kind of rosuvastatin calcium intermediate preparation method (by machine translation)
The invention relates to a kind of rosuvastatin calcium intermediate preparation method, the chemical name rosuvastatin calcium intermediate 6 - [(1 E) - 2 - [4 - (4 - fluorophenyl) - 6 - isopropyl - 2 - [methyl (methylsulfonyl) amino] - 5 - pyrimidine] vinyl] - 2, 2 - dimethyl - 1, 3 - dioxane - 4 - tert-butyl acetate, comprising the following steps: (1) the following formula 2 with the following formula 3 compound dissolved in an organic solvent and cooling, then water is added to the organic solvent, organic base, thermal insulation reaction; (2) after the reaction by adding saturated ammonium chloride solution quenching reaction, sequentially extraction, dehydration, filtering, and reducing pressure and extraction solvent, recrystallization, to obtain the target product. The invention tertiary butyl alcohol potassium as the organic base, cheap, high safety, and by adding a small amount of water in the reaction system to start the reaction, the reaction smoothly, quickly, to obtain the target product of the cis-isomer impurity can be controlled within 3% the following, the yield of 85% or more, than the existing technology has improved obviously. (by machine translation)
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Paragraph 0023-0026; 0027-0030; 0031-0034

(2017/11/16)

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.
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Paragraph 0020; 0021; 0022; 0023; 0024; 0025; 0026-0034

(2017/07/21)

PROCESSES FOR THE PREPARATION OF ROSUVASTATIN OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
The present invention relates to processes for the preparation of rosuvastatin calcium of formula I and pharmaceutically acceptable salts thereof using novel intermediates, and to a pharmaceutical composition containing the same.
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Page/Page column 28

(2016/09/22)

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.
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Paragraph 0054; 0055; 0056

(2016/10/10)

Ruishufatatinggan known method for the preparation of impurity
The invention relates to a preparation method of known impurities of rosuvastatin. The preparation method comprises the following step: by taking 4-(4-fluorophenyl)-5-triphenyl phosphine bromine-6-isopropyl-2-[(N-methyl-N-methanesulfonamido)]-pyrimidine as a raw material, preparing (bis-[E-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl) amino]-pyrimidine-yl]-3R-3-hydroxyl-5-oxo-6-heptenoic acid] calcium salt through witting reaction, acidification, oxidization, alkaline hydrolysis and salt forming reaction to obtain the known impurities of rosuvastatin. The preparation method is short in synthetic line and simple to operate, and the product obtained is high in purity and can be applied to research of reference substances.
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Paragraph 0030; 0031; 0038; 0039; 0046; 0047; 0054; 0055

(2019/02/02)

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.
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Paragraph 0051; 0052

(2017/03/21)

Process for the preparation of (E)-tert-butyl-2-(6-(2-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl,methylsulfonamido)pyrimidin-5-yl)vinyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate as a rosuvastatine intermediate
The present invention relates to a method for manufacturing (E)-tert-butyl-2-(6-(2-(4-(4-fluorophenyl)-6-isopropy l-2-(N-methyl,methylsulfonamido)pyrimidin-5-yl)vinyl)-2,2-dimethyl-1,3-dioxan-4-yl) acetate as rosubastatine intermediate that is frequently used for treating hyperlipidemia. According to the method for manufacturing in the present invention, (E)-tert-butyl-2-(6-(2-(4-(4-fluorophenyl)-6-isopropy-2-(N-methyl,methylsulfonamido)pyrimidin-5-yl)vinyl)-2,2-dimethyl-1,3-dioxan-4-yl) acetate as a rosubastatine intermediate made of solid with high and consistent purity can be mass-produced by using t-butyl 2-((4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4yl) acetate having optical activation in the form of solid with high purity.
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(2016/12/26)

AN IMPROVED PROCESS FOR THE PREPARATION OF CHIRAL DIOL SULFONES AND STATINS
The present invention relates to an improved process to prepare chiral diol sulfones of formula (I), wherein R1 and R2 each independently represent group selected from C1-4 alkyl, C1-4 alkenyl, C3-6 cycloalkyl, C6-10 aryl or C7-12 aralkyl, each of R1 and R2 may be substituted and wherein R1 and R2 may form a ring together with the C-atom; R3 represents group selected from C1-5 alkyl, aryl or aralkyl.
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(2014/07/23)

NOVEL INTERMEDIATES FOR THE PREPARATION OF HMG-CoA REDUCTASE INHIBITORS
The present invention provides a process for preparing novel intermediates of Formula wherein, R1 can be hydrogen, C1-C4 alkyl, halogen, nitro, hydroxy, or C1-C4 alkoxy; Rx can be selected from hydrophobic residue of HMG-CoA reductase inhibitors; which can be effectively used for the preparation of HMG-CoA reductase inhibitors such as rosuvastatin and pharmaceutically acceptable salts thereof.
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(2013/06/27)

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.
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(2012/08/07)

NOVEL METHOD FOR PREPARING ROSUVASTATIN, INTERMEDIATE COMPOUNDS USEFUL FOR PREPARING SAME, AND METHOD FOR PREPARING SAME
The present invention relates to novel intermediate compounds used in preparing Rosuvastatin or the pharmaceutically acceptable salts thereof, to a method for preparing same, and to a method for preparing Rosuvastatin or the pharmaceutically acceptable salts thereof from the intermediates. The preparation method of the present invention has the effect of providing Rosuvastatin hemi-calcium salts with an excellent yield rate.
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Page/Page column 13-14

(2012/06/16)

NOVEL INTERMEDIATES FOR THE PREPARATION OF HMG-CoA REDUCTASE INHIBITORS
The present invention provides a process for preparing novel intermediates of Formula wherein, R1 can be hydrogen, C1-C4 alkyl, halogen, nitro, hydroxy, or C1-C4 alkoxy; Rx can be selected from hydrophobic residue of HMG-CoA reductase inhibitors; which can be effectively used for the preparation of HMG-CoA reductase inhibitors such as rosuvastatin and pharmaceutically acceptable salts thereof.
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(2011/11/06)

PROCESS FOR THE PREPARATION OF DIHYDROXY PROTECTED DERIVATIVES AND NOVEL INTERMEDIATE COMPOUNDS
The present invention relates to an improved process for the preparation of dihydroxy protected derivatives, which are important intermediates in the preparation of HMG-CoA reductase inhibitors.
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Page/Page column 27

(2011/08/03)

NOVEL PYRIMIDINE DERIVATIVE AND METHOD FOR PRODUCING HMG-CoA REDUCTASE INHIBITOR INTERMEDIATE
The problem to be solved of the present application is to provide a method for producing a novel pyrimidine derivative from an inexpensive compound which is industry-available with ease, and a method for producing an important intermediate of an HMG-CoA reductase inhibitor. The problem can be solved by, for example, reacting the compound (1) with the compound represented by (OR1) 3P to obtain the phosphonate ester (3) and reacting the phosphonate ester (3) with the compound (4) in the presence of a base to obtain an HMG-CoA reductase inhibitor intermediate (5).
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Page/Page column 11

(2011/08/08)

A PROCESS FOR PREPARATION OF ROSUVASTATIN INTERMEDIATE
The present invention provides an improved process for the preparation of intermediates involved in the preparation of rosuvastatin. Particularly, the proposed invention is able to overcome the disadvantages associated with the known methods. Thus, the instant invention provides a process which is clean, economic, industrially scalable and provides high yields with substantially pure product.
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Page/Page column 18; 19

(2010/04/06)

A PROCESS FOR PREPARING HMG-COA REDUCTASE INHIBITORS AND INTERMEDIATES
The present invention relates to an improved process for synthesizing calcium salt of (E)-7-[4-(4-flurophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino] pyrimidin-5-yl](3R,5S)-3,5-dihydroxy-6-heptenoic acid (Rosuvastatin Calcium) in high purity.
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Page/Page column 37: 48-49

(2010/01/30)

Chemical Process
A process for formation of a compound of formula (I) or a pharmaceutically acceptable salt thereof, (A chemical formula should be inserted here—please see paper copy enclosed herewith) I via a Heck reaction is described. Intermediates useful in the process and processes for making said intermediates are also described.
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Page/Page column 16

(2008/12/08)

NOVEL PROCESS FOR STATINS AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
Novel process for statins and its pharmaceutically acceptable salts thereof represented by general formula (I).
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Page/Page column 55; 69

(2008/06/13)

Process for the preparation of pyrimidine derivatives
An improved process for the preparation of pyrimidine derivatives is provided comprising reacting a Wittig reagent of the general formula wherein R is an alkyl of from 1 to 10 carbon atoms, aryl or arylalkyl, R1 is a substituted or unsubstituted hydrocarbon group, R2 and R3 are the same or different and are hydrogen or a substituted or unsubstituted hydrocarbon group; Z is sulfur, oxygen, sulfonyl, or imino which may be substituted by formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, amino substituted by sulfonyl or alkylsulfonyl, and sulfonyl substituted by alkyl, amino or alkylamino and X is a halogen; with an aldehyde of the general formula wherein R4 is hydrogen, a lower alkyl or a cation capable of forming a non-toxic pharmaceutically acceptable salt and each R5 are the same or different and are hydrogen or a hydrolyzable protecting group, or each R5, together with the oxygen atom to which each is bonded, form a hydrolyzable cyclic protecting group, or each R5 is bonded to the same substituent which is bonded to each oxygen atom to form a hydrolyzable protecting group; in the presence of a base.
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Page/Page column 8-9; 10

(2010/02/11)

Process for the production of tert-butyl (E)-(6-[2-[4-(-flourophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]vinyl](4R,6S)-2, 2-dimethyl[1, 3]oioxan-4yl)acetace
The invention concerns a process for the manufacture of tert-butyl (E)-(6-[2-4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]vinyl}-(4R, 6S)-2,2-dimethyl[1,3-dioxan-4-yl) acetate, the novel starting material used in said process and the use of the process in the manufacture of a pharmaceutical.
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Page 3

(2010/02/05)

PROCESS FOR THE PREPARATION OF PYRIMIDINE DERIVATIVES
There is described a process for the preparation of compounds of formula (1) starting from the reaction of the compounds of formulae (24), (25) and (26) to form the compound of formula (23), wherein in each case R1, R2 and R3 are each independently of the others an unsubstituted or substituted organic radical; R4 is hydrogen, unsubstituted or substituted C1-C8alkyl, C1-C8alkoxy, phenoxy or benzyloxy, or halogen; Y1 and Y2 are each independently of the other hydrogen or a protecting group, or Y1 and Y2 together are a protecting bridge; and X1 is hydrogen, an organic radical or a cation; and also novel intermediates.
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Page 25-26

(2010/02/09)