![N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide](/Databaselist/images/loading.webp)
147118-37-4Relevant academic research and scientific papers
An efficient approach to the key intermediate of rosuvastatin
Guan, Yueqing,Zhou, Guobin,Yang, Weiqun
, p. 11 - 13 (2014)
An efficient synthetic approach to the synthesis of the 5-pyrimidinecarbaldehyde 2, which is the key intermediate of rosuvastatin, involves the aerobic oxidation of the 5-pyrimidinemethanol 1 in the presence of Co(NO3)2, dimethylglyoxime (DmgH2), and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) under mild reaction conditions. The method does not require the use of hazardous or expensive chemicals and is suitable for scale-up.
Synthesis method of rosuvastatin calcium intermediate
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Paragraph 0023; 0038-0052, (2021/06/23)
The invention discloses a synthesis method of a rosuvastatin calcium intermediate, a matrix is as follows: 4-(4-fluorophenyl)-6-isopropyl-2-[(N-methyl-N-methylsulfonyl) ammonia] pyrimidine-5-methanol; under the catalytic action of a mixed salt and 2, 2, 6, 6-tetramethylpiperidine oxygen by taking air as an oxidizing agent, the rosuvastatin calcium intermediate 4-(4-fluorophenyl)-6-isopropyl-2-[(N-methyl-N-methylsulfonyl) ammonia] pyrimidine-5-methanal is generated. The mixed salt is common nitrate and halide salt, the price is low, the oxidizing agent is air, the source is convenient, and the production cost is greatly reduced; meanwhile, the method has the advantages of few three wastes, environment friendliness, mild and controllable reaction conditions, high yield and high product purity, and is suitable for large-scale production.
Method for preparing rosuvastatin calcium intermediate
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Paragraph 0046-0060, (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.
An isocyanide ligand for the rapid quenching and efficient removal of copper residues after Cu/TEMPO-catalyzed aerobic alcohol oxidation and atom transfer radical polymerization
Bulska, Ewa,Enciso, Alan E.,Fantin, Marco,Grela, Karol,Lorandi, Francesca,Matyjaszewski, Krzysztof,Nogas, Wojciech,Piatkowski, Jakub,Ruszczynska, Anna,Szczepaniak, Grzegorz,Yerneni, Saigopalakrishna S.
, p. 4251 - 4262 (2020/05/13)
Transition metal catalysts play a prominent role in modern organic and polymer chemistry, enabling many transformations of academic and industrial significance. However, the use of organometallic catalysts often requires the removal of their residues from reaction products, which is particularly important in the pharmaceutical industry. Therefore, the development of efficient and economical methods for the removal of metal contamination is of critical importance. Herein, we demonstrate that commercially available 1,4-bis(3-isocyanopropyl)piperazine can be used as a highly efficient quenching agent (QA) and copper scavenger in Cu/TEMPO alcohol aerobic oxidation (Stahl oxidation) and atom transfer radical polymerization (ATRP). The addition ofQAimmediately terminates Cu-mediated reactions under various conditions, forming a copper complex that can be easily separated from both small molecules and macromolecules. The purification protocol for aldehydes is based on the addition of a small amount of silica gel followed byQAand filtration. The use ofQA?SiO2synthesizedin situresults in products with Cu content usually below 5 ppm. Purification of polymers involves only the addition ofQAin THF followed by filtration, leading to polymers with very low Cu content, even after ATRP with high catalyst loading. Furthermore, the addition ofQAcompletely prevents oxidative alkyne-alkyne (Glaser) coupling. Although isocyanideQAshows moderate toxicity, it can be easily converted into a non-toxic compound by acid hydrolysis.
A Simple, Mild and General Oxidation of Alcohols to Aldehydes or Ketones by SO2F2/K2CO3 Using DMSO as Solvent and Oxidant
Zha, Gao-Feng,Fang, Wan-Yin,Leng, Jing,Qin, Hua-Li
supporting information, p. 2262 - 2267 (2019/04/17)
A practical, general and mild oxidation of primary and secondary alcohols to carbonyl compounds proceeds in yields of up to 99% using SO2F2 as electrophile in DMSO as both the oxidant and the solvent at ambient temperature. No moisture- and oxygen-free conditions are required. Stoichiometric amount of inexpensive K2CO3, which generates easy to separate by-products, is used as the base. Thus, 5-gram scale runs proceeded in nearly quantitative yields by a simple filtration as the work-up. The use of a polar solvent such as DMSO, which usually promotes competing Pummerer rearrangement, is also noteworthy. This protocol is compatible with a variety of common N-, O-, and S-functional groups on (hetero)arene, alkene and alkyne substrates (68 examples). The protocol was applied (99% yield) to a formal synthesis of the important cholesterol-lowering drug Rosuvastatin. (Figure presented.).
A method for preparing a rosuvastatin calcium intermediate
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Paragraph 0023; 0027, (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.
NH3?H2O: The Simplest Nitrogen-Containing Ligand for Selective Aerobic Alcohol Oxidation to Aldehydes or Nitriles in Neat Water
Zhang, Guofu,Ma, Danting,Zhao, Yiyong,Zhang, Guihua,Mei, Guangyao,Lyu, Jinghui,Ding, Chengrong,Shan, Shang
, p. 885 - 889 (2018/12/10)
Aqueous ammonia (NH3?H2O) has been shown to serve as the simplest nitrogen-containing ligand to effectively promote copper-catalyzed selective alcohol oxidation under air in water. A series of alcohols with varying electronic and steric properties were selectively oxidized to aldehydes with up to 95 % yield. Notably, by increasing the amount of aqueous ammonia in neat water, the exclusive formation of aryl nitriles was also accomplished with good-to-excellent yields. Additionally, the catalytic system exhibits a high level of functional group tolerance with ?OH, ?NO2, esters, and heteroaryl groups all being amenable to the reaction conditions. This one-pot and green oxidation protocol provides an important synthetic route for the selective preparation of either aldehydes or nitriles from commercially available alcohols.
A formyl rosuvastatin salts calcium intermediate preparation method
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, (2017/10/28)
The invention discloses a preparation method of a formoxyl rosuvastatin calcium intermediate. With 2-methyl-3-carbonyl valeronitrile, 4-fluorobenzaldehyde and urea as raw materials, the formoxyl rosuvastatin calcium intermediate 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-formoxyl-2-(N-methyl-N-methylsulfonyl) pyrimidine is synthesized by reactions such as cyclization, oxidation, N-substitution and reduction. Compared with an existing method, the method has the advantages that reaction conditions are mild, the used reagent is relatively cheap and the yield is high.
Synthetic method of rosuvastatin calcium key intermediate
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, (2016/10/10)
The invention discloses a synthetic method of a rosuvastatin calcium key intermediate. The synthetic method particularly comprises the following steps: carrying out a condensation reaction between fluoroacetophenone and ethyl isobutyrate under the condition of using sodium as alkali by using isopropyl alcohol as a solvent to prepare 1-(4-fluorophenyl)-4-methyl amyl-1,3-diketone; then carrying out a ring closing reaction between the 1-(4-fluorophenyl)-4-methyl amyl-1,3-diketone and methylguanidine hydrochloride by using isopropanol as a solvent to obtain 4-(4-fluorophenyl)-6-isopropyl-N-methyl pyrimidine-2-amine; carrying out a substitution reaction between the 4-(4-fluorophenyl)-6-isopropyl-N-methyl pyrimidine-2-amine and methanesulfonyl chloride by using dichloromethane as a solvent to obtain 4-(4-fluorophenyl)-6-isopropyl-2-[(N-methyl-N-methanesulfonyl) amino] pyrimidine; finally, carrying out a Vilsmeier reaction between the 4-(4-fluorophenyl)-6-isopropyl-2-[(N-methyl-N-methanesulfonyl) amidogen] pyrimidine and DMF (Dimethyl Formamide) as well as phosphoryl chloride to obtain a target compound. The method disclosed by the invention has the advantages of being simple to operate, low in raw material price, high in availability of used raw materials, mild in reaction conditions, low in equipment requirements and production cost, easy for scale production and the like, and has significance industrial application value.
Method used for synthesizing rosuvastatin calcium key intermediate
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, (2016/10/10)
The invention discloses a method used for synthesizing a rosuvastatin calcium intermediate represented by formula I. The reaction route is disclosed in the invention. Raw materials used in the method are low in toxicity; synchronous recycling of used solvents can be realized; expensive materials such as 4-methylmorpholine-N-oxide, TPAP (tetrapropylammonium perruthenate), and DIBAL-H are not used, so that production cost is reduced effectively; reaction conditions are mild; energy consumption is low; no special reaction equipment is needed; operation is simple; one-pot preparation can be realized; and the method is convenient for large-scale production.
