147118-36-3Relevant articles and documents
Synthesis, characterization and crystal structure of N-(4-(4-Fluorophenyl)-5-(hydroxymethyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide
Xu, Jia-Ying,Cheng, Wei-Hua,Zhu, Xun,Wu, Huan-Ling,Wang, Kai
, p. 7766 - 7768 (2014)
N-[4-(4-Fluorophenyl)-5-(hydroxymethyl)-6-isopropylpyrimidin-2-yl]-N-methylmethane sulfonamide (I), an important intermediate to synthesize rosuvastatin, an HMG-CoA reductase inhibitor. It was prepared from methyl 4-(4-fluorophenyl)-6-isopropyl-2-(methylamino)pyrimidine-5-carboxylate (1) via mesylation by mesyl chloride and sodium tert-pentoxide, then reduction by DIBAL/HCl. The product was characterized by NMR and LC-MS. The crystal structure of compound I was investigated using X-ray diffraction and SHELXTL-97 software. The result indicated that compound I crystallized in the monoclinic system, space group C2/C with a = 29.683(6), b = 7.6290 (15), c = 18.215(4) ?, V = 3451.1 (16) ?3; Z 8.
An efficient, cyanide free total synthesis of rosuvastatin calcium
Vempala, Naresh,Matta, Balaji,Rao, S. Venkateswara,Maddirala, Shambabu Joseph,Shree, A. Jaya
, (2022/03/27)
A simple, efficient, cyanide-free protocol for the total synthesis of rosuvastatin calcium was developed from inexpensive, commercially available D-arabinose; the key steps employed were Wittig reaction followed by oxa-Michael addition. The developed synthetic protocol could be adopted for industrial production of rosuvastatin calcium.
Method for preparing rosuvastatin calcium intermediate
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Paragraph 0025-0045, (2020/04/17)
The invention discloses a preparation method for synthesizing a rosuvastatin calcium intermediate. The method comprises the following steps: taking 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonyl-2-(N-methyl-N-methane sulfonamide) pyrimidine ester shown as formula (II) as a raw material; adding a metal borohydride, in an inert organic solvent, adding BF3 at the temperature of -20 DEG Cto 20 DEG C; raising the temperature to 40-100 DEG C and reacting; treating an obtained reacted solution A, and dissolving obtained 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonyl-2-(N-methyl-N-methanesulfonamido) pyrimidine-5-methanol shown as formula (III) in an organic solvent; adding a catalyst and a co-catalyst, reacting fully at 20 to 100 DEG C at the air or oxygen atmosphere to obtain a reaction solution B, and carrying out aftertreatment on the reaction solution B to obtain 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonyl-2-(N-methyl-N-methane sulfonamide) pyrimidine-5-formaldehyde as shown in formula (IV). The method is mild in condition and simple in aftertreatment, the production cost is reduced, and the molar yield of the product is high.
Resuvastatin calcium parent nuclei and synthesis method thereof
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Paragraph 0041-0078, (2019/05/22)
The invention discloses resuvastatin calcium nuclei and a synthesis method thereof and relates to the technical field of drug intermediate synthesis. The synthesis method includes following steps: 1),under protection effect of inert gas, taking 4-(4-fluorophenyl)-6-isopropyl-2-[(N-methyl-N-methylsulfonyl)amino]pyrimidine-5-methyl formate as a starting raw material, and adding the same into an organic solvent; 2), adding sodium disulfide, dropwise adding an organic solvent solution of red aluminum, rising temperature to 35-45 DEG C, and allowing reaction for 3-5h to obtain an initial product;3), quenching, separating, drying, evaporating to remove the solvent, and recrystallizing to obtain the resuvastatin calcium nuclei. The synthesis method is short in reaction process, simple in process, mild in reaction condition and convenient for control, can directly realize layering of different phases in the process of quenching, does not generate a lot of solid aluminum salt, does not causethe problem that the resuvastatin calcium nuclei are difficult to treat caused by the fact that the solid aluminum salt adsorbs the resuvastatin calcium nuclei, does not generate big impurities and ishigh in product purity and yield.
A method for preparing a rosuvastatin calcium intermediate
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Paragraph 0024, (2019/01/08)
The invention relates to the technical field of pharmaceutical chemistry, particularly the field of process optimization and cost control for pharmaceutical intermediate preparation, and more particularly relates to an impurity in preparation of a rosuvastatin calcium intermediate and a method for synthesizing the intermediate from the impurity. A compound I' is reacted with ozone and a reductantto obtain a compound IV and an important intermediate III, the compound IV is further subjected to reduction and substitution to prepare another intermediate II important in preparation of the rosuvastatin calcium intermediate, and the compound II and the compound III are adopted to prepare an intermediate compound I. Through recovery and utilization of the impurity compound I', the preparation cost of the compound I is significantly reduced. The method is simple in process and suitable for industrial large-scale production.
Palladium-Catalyzed Stereoselective Cyclization of in Situ Formed Allenyl Hemiacetals: Synthesis of Rosuvastatin and Pitavastatin
Spreider, Pierre A.,Breit, Bernhard
supporting information, p. 3286 - 3290 (2018/06/11)
A diastereoselective palladium-catalyzed cyclization of allenyl hemiacetals is described. It permits the selective synthesis of 1,3-dioxane derivatives, precursors for syn-configured 1,3-diols which make an appearance in all of the statin representatives. The reaction allows the total synthesis of Rosuvastatin and Pitavastatin in a straightforward fashion.
Method for synthesizing rosuvastatin calcium intermediate impurity
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Paragraph 0014-0018, (2018/07/30)
The invention discloses a method for synthesizing a rosuvastatin calcium intermediate impurity. The method comprises the following steps: preparing 4-(4-fluorophenyl)-6-isopropyl-2-[(N-methyl-N-methylsulfonyl) amino] pyrimidine-5-methanol (3) from 4-(4-fluorophenyl)-6-isopropyl-2-[(N-methyl-N-methylsulfonyl) amino] pyrimidine-5-methyl carboxylate (2) through reduction; preparing 5-(bromine methyl)-4-(4-fluorophenyl)-6-isopropyl-2-[methyl (methylsulfonyl) amino] pyrimidine (4) from the compound (3) through bromination; coupling the compound (4) with the 4-(4-fluorophenyl)-6-isopropyl-2-[(N-methyl-N-methylsulfonyl) amino] pyrimidine-5-methanol (3) to generate N,N'-(5,5'-(oxo-di(methylene)) bi(4-(4-fluorophenyl)-6-isopropyl pyrimidine-5,2-di-yl)) bi(N-methyl methanesulfonamide) (1), so as toobtain the rosuvastatin calcium intermediate impurity with high impurity. The synthesized rosuvastatin calcium intermediate impurity can be used as an impurity standard substance in rosuvastatin calcium raw material detection and analysis, and accurate positioning and qualification of impurities in rosuvastatin calcium raw material detection and analysis can be improved; the method disclosed by the invention is cheap and easy in raw material obtaining and simple in operation, the product yield is 65+/-5%, and the HPLC (High Performance Liquid Chromatography) purity is greater than or equal to99%.
Efficient Construction of the Nucleus of Rosuvastatin Calcium
Zhou, Yingtao,Lin, Chenhui,Xing, Yuzhi,Chen, Ligong,Yan, Xilong
, p. 1898 - 1903 (2017/05/29)
A novel and efficient five-step synthetic route, including a Biginelli reaction, dehydrogenation, chlorination, sulfonamidation, and reduction, for the core of Rosuvastatin was established. All steps were systematically studied. Tert-butylhydroperoxide aqueous solution was applied in the dehydrogenation instead of nitric acid. N,N-dimethylaniline was employed as a catalyst to accelerate the chlorination proceeding smoothly, and its catalytic mechanism is discussed. In the sulfonamidation, the conversion of compound 5 was obviously improved by use of NaH and acetonitrile. In addition, two sulfonamidation side products 6 and 7 were detected and isolated. Thus, under the optimized reaction conditions, the target product was obtained in 60.4% total yield, much higher than the reported yield (36.4%).
Preparation method of rosuvastatin calcium intermediate
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, (2017/10/23)
The invention provides a preparation method of a rosuvastatin calcium intermediate. The preparation method of the rosuvastatin calcium intermediate, namely, the compound shown as formula I in the description comprises the following steps: (1) a compound 5 shown as formula II in the description is generated from 4-fluorobenzaldehyde, methyl isobutyrylacetate and urea under the action of a catalyst; (2) a compound 6 shown as formula III in the description is generated from the compound 5 under the action of potassium persulfate as an oxidizing agent; (3) a compound 7 shown as formula IV in the description is generated from the compound 6, tosyl chloride and N-methyl methanesulfonamide under the action of a catalyst; (4) the target compound shown as the formula I is generated from the compound 7 under the action of a vitride solution as a reducing agent and crystallized with a crystallization solution, and a purified target compound is obtained. The preparation method of the rosuvastatin calcium intermediate has the advantages of low production cost, mild condition and simple and convenient operation.
METHOD FOR PREPARING ROSUVASTATIN SODIUM
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Paragraph 0041; 0042, (2017/07/14)
The present invention belongs to the technical field of organic chemistry, and specifically relates to a method for preparing rosuvastatin sodium. The method of the invention comprises: reducing 4-p-fluorophenyl-6-isopropyl-2-(N-methyl-methylsulfonylamino)pyrimidine-5-carboxylic acid (VII) in the presence of a borohydride, an alkyl-substituted chlorosilane and an assistance in an organic solvent to prepare 4-p-fluorophenyl-5-hydroxymethyl-6-isopropyl-2-(N-methyl-methylsulfonylamino) pyrimidine (VIII); then performing a reaction of the compound VIII with a triphenyl phosphonium salt in an organic solvent to prepare a ((4-p-fluorophenyl-6-isopropyl-2-(N-methyl-methylsulfonylamino)-5-pyridyl)-methyl)triphenyl phosphonium salt (IX); performing a stereoselective Michael addition reaction of (S)-trans-4,5-dihydroxy-pent-2-olefine acid ester (II) with furfural (III) to prepare a 2-((4R,6S)-2-(furan-2-yl)-6-hydroxymethyl-1,3-dioxane-4-yl)acetate (IV); oxidizing the compound IV to prepare a 2-((4R,6S)-2-(furan-2-yl)-6-formacyl-1,3-dioxane-4-yl)acetate (V); performing an olefination reaction of the compound V with the (4-p-fluorophenyl-6-isopropyl-2-(N-methyl-methylsulfonylamino)pyrimid-5-yl)-methyl triphenyl substituted phosphonium salt (IX) or phosphate to prepare 2-((4R,6S)-6-(trans-2-(4-p-fluorophenyl-6-isopropyl-2-(N-methyl-methylsulfonylamino)pyrimid-5-yl)vinyl)-2-(furan-2-yl)-1,3-dioxane-4-yl)acetate (VI); and performing deprotection and sodium salt formation of compound VI to prepare rosuvastatin sodium (I). The method has easily obtainable raw materials, and is simple to operate and suitable for industrial productions.
