cas 147118-37-4, 4-(4-Fluorophenyl)-6-isopropyl-2-[(N-methyl-N-methylsulfonyl)amino]pyrimidinyl-5-yl-formyl

Articles about 147118-37-4Total 29 be found

Article title
Article abstract
Author
Journal number and time
Download

An efficient approach to the key intermediate of rosuvastatin
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.
Guan, Yueqing,Zhou, Guobin,Yang, Weiqun
p. 11 - 13
(2014)
Read Online

Synthesis method of rosuvastatin calcium intermediate
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.
-
Paragraph 0023; 0038-0052

(2021/06/23)

Method for preparing rosuvastatin calcium intermediate
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.
-
Paragraph 0046-0060

(2020/04/17)

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
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.
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)

A Simple, Mild and General Oxidation of Alcohols to Aldehydes or Ketones by SO2F2/K2CO3 Using DMSO as Solvent and Oxidant
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.).
Zha, Gao-Feng,Fang, Wan-Yin,Leng, Jing,Qin, Hua-Li
supporting information
p. 2262 - 2267
(2019/04/17)

A method for preparing a rosuvastatin calcium intermediate
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.
-
Paragraph 0023; 0027

(2019/01/08)

NH3?H2O: The Simplest Nitrogen-Containing Ligand for Selective Aerobic Alcohol Oxidation to Aldehydes or Nitriles in Neat Water
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.
Zhang, Guofu,Ma, Danting,Zhao, Yiyong,Zhang, Guihua,Mei, Guangyao,Lyu, Jinghui,Ding, Chengrong,Shan, Shang
p. 885 - 889
(2018/12/10)

A formyl rosuvastatin salts calcium intermediate preparation method
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.
-
(2017/10/28)

Method used for synthesizing rosuvastatin calcium key intermediate
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.
-
(2016/10/10)

Synthetic method of rosuvastatin calcium key intermediate
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.
-
(2016/10/10)

Preparation method of rosuvastatin calcium key intermediate
The invention discloses a preparation method of a rosuvastatin calcium key intermediate, i.e. a compound as shown in a formula I. The preparation method comprises the following steps: a, carrying out a reaction between fluoroacetophenone and ethyl isobutyrate to prepare a compound as shown in a formula IV; b, carrying out a reaction between the obtained compound IV and methylguanidine hydrochloride as well as potassium hydroxide to obtain a compound as shown in a formula III; c, carrying out a reaction between the compound III and triethylamine as well as methanesulfonyl chloride to prepare a compound as shown in a formula II; d, carrying out a reaction between the compound as shown in the formula II and N,N-dimethylformamide as well as phosphorus oxychloride to obtain the compound as shown in the formula I. A reaction route of the preparation method is as shown in the following: (referring to the specification). 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.
-
(2016/12/22)

IMPROVED PROCESS FOR PREPARING STATIN PRECURSOR
The present invention relates to a process for preparing a statin precursor, which process comprises a first reaction step, wherein a hydroxy-pyrimidine-carbonitrile is reacted with an organic sulfonyl halide to form the sulfonate-pyrimidine-carbonitrile; a second reaction step, wherein the sulfonate-pyrimidine-carbonitrile is reacted with N-methylmethane sulfonamide to form a pyrimidinyl-sulfonamide; and optionally a third reaction step, wherein the pyrimidinyl-sulfonamide is reacted with a reducing agent. All steps are conducted in toluene as the main solvent.
-
Page/Page column 13; 14

(2016/12/22)

Stable TEMPO and ABNO Catalyst Solutions for User-Friendly (bpy)Cu/Nitroxyl-Catalyzed Aerobic Alcohol Oxidation
Two solutions, one consisting of bpy/TEMPO/NMI and the other bpy/ABNO/NMI (bpy =2,2′-bipyridyl; TEMPO = 2,2,6,6-tetramethylpiperidine N-oxyl, ABNO = 9-azabicyclo[3.3.1]nonane N-oxyl; NMI = N-methylimidazole), in acetonitrile are shown to have good long-term stability (≥1 year) under air at 5 °C. The solutions may be combined in appropriate quantities with commercially available [Cu(MeCN)4]OTf to provide a convenient catalyst system for the aerobic oxidation of primary and secondary alcohols.
Steves, Janelle E.,Stahl, Shannon S.
p. 11184 - 11188
(2015/11/18)

Process Development of CuI/ABNO/NMI-Catalyzed Aerobic Alcohol Oxidation
An improved Cu/nitroxyl catalyst system for aerobic alcohol oxidation has been developed for the oxidation of functionalized primary and secondary alcohols to aldehydes and ketones, suitable for implementation in batch and flow processes. This catalyst, which has been demonstrated in a >50 g scale batch reaction, addresses a number of process limitations associated with a previously reported (MeObpy)CuI/ABNO/NMI catalyst system (MeObpy = 4,4′-dimethoxy-2,2′-bipyridine, ABNO = 9-azabicyclo[3.3.1]nonane N-oxyl, NMI = N-methylimidazole). Important catalyst modifications include the replacement of [Cu(MeCN)4]OTf with a lower-cost Cu source, CuI, reduction of the ABNO loading to 0.05-0.3 mol%, and use of NMI as the only ligand/additive (i.e., without a need for MeObpy). Use of a high flash point solvent, N-methylpyrrolidone, enables safe operation in batch reactions with air as the oxidant. For continuous-flow applications compatible with elevated gas pressures, better performance is observed with acetonitrile as the solvent.
Steves, Janelle E.,Preger, Yuliya,Martinelli, Joseph R.,Welch, Christopher J.,Root, Thatcher W.,Hawkins, Joel M.,Stahl, Shannon S.
p. 1548 - 1553
(2015/12/01)

Synthesis and antimicrobial activity of new S-alkyl isothiosemicarbazone derivatives of pyrimidine
A series of S-alkyl isothiosemicarbazone derivatives of 2,4,6-trisubstituted pyrimidine have been synthesized. All the synthesized compounds are characterized by IR, NMR and mass spectrometry. Most of the synthesized compounds show significant antibacterial and antifungal activity against the tested microorganisms.
Raundal, Hemant N.,Jadhav, Rahul P.,Patil, Amar A.,Mhaske, Pravin C.,Bobade, Vivek D.
p. 565 - 569
(2015/04/27)

Metal-free, visible-light photoredox catalysis: Transformation of arylmethyl bromides to alcohols and aldehydes
A mild, simple, and controllable metal-free photocatalytic system for the transformation of arylmethyl bromides to corresponding alcohols and aldehydes in high yields with visible-light irradiation has been achieved. Eosin Y was found to be an efficient promoter for this oxidative dehalogenation reaction under photo irradiation conditions.
Li, Jian,Wang, Hongni,Liu, Li,Sun, Jiangtao
p. 49974 - 49978
(2014/12/10)

PROCESS FOR THE PREPARATION OF KEY INTERMEDIATES FOR THE SYNTHESIS OF STATINS OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
The invention relates to commercially viable process for the synthesis of key intermediates for the preparation of statins, in particular Rosuvastatin and Pitavastatin or respective pharmaceutically acceptable salts thereof. A new simple and short synthetic route for key intermediates is presented which benefits from the use of cheap and readily available starting materials, by which the conventionally most frequently used DIBAL-H as reducing agent can be avoided.
-
Page/Page column 62

(2012/02/13)

Process for the preparation of key intermediates for the synthesis of statins or pharmaceutically acceptable salts thereof
The invention relates to commercially viable process for the synthesis of key intermediates for the preparation of statins, in particular Rosuvastatin and Pitavastatin or respective pharmaceutically acceptable salts thereof. A new simple and short synthetic route for key intermediates is presented which benefits from the use of cheap and readily available starting materials, by which the conventionally most frequently used DIBAL-H as reducing agent can be avoided.
-
Page/Page column 55

(2012/03/26)

Concise and highly efficient approach to three key pyrimidine precursors for rosuvastatin synthesis
We report the synthesis of 5-formyl-, 5-(hydroxymethyl)-, and 5-(bromomethyl) substituted N-[4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl]-N- methylmethanesulfonamide. The presented synthetic approach is based on highly efficient three step preparation of functionalized 5-methylpyrimidine. The methyl group is selectively brominated by NBS with irradiation into the bromomethyl derivative, which is then transformed into the hydroxymethyl or formyl groups in nearly quantitative yields. This approach is superior to the existing methodologies for the preparation of the key pyrimidine precursors used in the synthesis of rosuvastatin since no metal catalysis and no cryogenic reaction conditions are involved.
?terk, Damjan,?asar, Zdenko,Juki?, Marko,Ko?mrlj, Janez
experimental part
p. 2155 - 2160
(2012/03/27)

PROCESS FOR PREPARATION OF ROSUVASTATIN CALCIUM
Disclosed is the process for the preparation of 4-(fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)-5-formyl-pyrimidine of formula (I), which is the intermediate of rosuvastatin calcium. Purification of substantially pure acetonide protected tert-butyl ester of rosuvastatin (II) and its use for the preparation of substantially pure amorphous rosuvastatin calcium are also disclosed.
-
Page/Page column 21-22

(2013/02/28)

PROCESS FOR PREPARING PYRIMIDINE DERIVATIVES
The present invention relates to a process for preparing pyrimidine derivatives, in particular as intermediates useful for preparing pyrimidine derivatives of a class that is effective at inhibiting the biosynthesis of cholesterol in humans, such as HMG-CoA reductase inhibitors, e.g. rosuvastatin.
-
Page/Page column 17

(2009/04/25)

A PROCESS FOR THE PREPARATION OF INTERMEDIATES OF ROSUVASTATIN
The present invention provides a process for the preparation of the rosuvastatin intermediates and their conversion to rosuvastatin or its pharmaceutically acceptable salts thereof.
-
Page/Page column 8; 17-18; 22-23

(2008/12/05)

A new approach to the total synthesis of rosuvastatin
A new multi-step synthesis of the lipid-lowering agent rosuvastatin, involving two homogeneously catalyzed reaction steps, is described. The key building block, N-[4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl]-N- methylmethanesulfonamide (2), was prepared by Pd-catalyzed formylation with CO/H2 (1:1, 50 bar, phosphane ligand/substrate ratio of 1:10). Several alternative pathways for the preparation of 2 were also tested, but were found to be inferior. Rosuvastatin precursor 1 was assembled by Wittig coupling of aldehyde 2 and ylide (R)-3, derived from a Rucatalyzed asymmetric hydrogenation. The second stereogenic center was finally created by stereoselective reduction with Et2BOMe and NaBH4 to afford rosuvastatin ethyl ester. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
Andrushko, Natalia,Andrushko, Vasyl,Koenig, Gerd,Spannenberg, Anke,Boerner, Armin
experimental part
p. 847 - 853
(2009/04/11)

PREPARATION OF ALKYL 4-(4-FLUOROPHENYL)-6-ISOPROPYL-2-[METHYL(METHYLSULFONY)AMINO]-PYRIMIDINE-5-CARBOXYLATE AND ITS SUBSEQUENT CONVERSION TO N-[4-(4-FLUOROPHENYL)-5-FORMYL-6-ISOPROPYL PYRIMIDIN-2-YL]-N-METHYLMETHANESULFONAMIDE-A KEY INTERMEDIATE IN THE SYNTHESIS OF ROSUVASTATIN
The present invention discloses a novel process to prepare a compound of formula (IIA). By reacting a compound of formula-[D], wherein R1 is C1 to C6 alkyl, preferably R1 is methyl or ethyl, more preferably R1 is methyl ; and R2 is C1 to C8 n-alkyl or branched alkyl, cycloalkyl, phenyl , benzyl or substituted phenyl group, preferably R2 is methyl ; with N-methyl methanesulfonamide and a base, optionally with a salt of N-methyl methanesulfonamide, in suitable solvent(s) , to give a compound of formula (IIA), followed by converting compound of formula (IIA) to a compound for formula -[B], by a known process and finally converting a compound of formula (B) to a compound of formula (II), by a novel process using calcium hypochlorite / TEMPO as an oxidant.
-
Page/Page column 16

(2008/06/13)

A PROCESS FOR THE PREPARATION OF ROSUVASTATIN INVOLVING A TEMPO-MEDIATED OXIDATION STEP
The present invention provides a process for the preparation of the rosuvastatin intermediate FPP-CHO and its conversion to rosuvastatin and pharmaceutically acceptable salts thereof.
-
Page/Page column 11-12

(2010/10/20)

Processes to produce intermediates for rosuvastatin
Intermediate compounds for preparing rosuvastatin are prepared by a process comprising oxidizing hydroxy groups to aldehyde groups, using sodium hypochlorite and 2,2,6,6-tetramethyl piperidinyl oxy free radical (TEMPO) as a catalyst.
-
Page/Page column 2-3

(2008/06/13)

PROCESS FOR THE PREPARATION OF N-[4-(4-FLUOROPHENYL)-5-FORMYL-6-ISOPROPYL-PYRIMIDIN-2-YL]-N-METHYLMETHANESULFONAMIDE
The present invention is directed to a method for the preparation of N-[4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide and its use in the preparation of rosuvastatin or a pharmaceutically acceptable salt thereof.
-
Page/Page column 11

(2008/06/13)

PROCESS FOR THE PREPARATION OF ROSUVASTATIN
The present invention relates to a cost effective and industrially advantageous process for the preparation of 4-4(fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulphonylamino)-5-pyrimidinecarboxaldehyde, referred to here as pyrimidine aldehyde of structural Formula I and to the use of this compound as intermediate for the preparation of rosuvastatin.
-
Page/Page column 4; 12

(2008/06/13)

Synthesis and biological activity of methanesulfonamide pyrimidine- and N-methanesulfonyl pyrrole-substituted 3,5-dihydroxy-6-heptenoates, a novel series of HMG-CoA reductase inhibitors
A novel series of methanesulfonamide pyrimidine- and N-methanesulfonyl pyrrole-substituted 3,5-dihydroxy-6-heptenoates were synthesized and evaluated for their ability to inhibit the enzyme HMG-CoA reductase in vitro. Monocalcium bis(+)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N- methanesulfonylaminopyrimidin)-5-yl]-(3R,5S)-dihydroxy- (E)-6-heptenoate (3a, S-4522) was selected as a candidate for further evaluation. Compound 3a was approximately four times more potent than lovastatin sodium salt (in inhibiting HMG-CoA reductase in vitro (IC50 = 11 nM). Compound 3a was shown to be the most potent cholesterol biosynthesis inhibitor in this series (IC50 = 1.12 nM) in rat isolated hepatocytes; its inhibitory activity was approximately 100 times more potent than pravastatin.
Watanabe, Masamichi,Koike, Haruo,Ishiba, Teruyuki,Okada, Tetsuo,Seo, Shujiro,Hirai, Kentaro
p. 437 - 444
(2007/10/03)