- Processes for the Preparation of Zuclomiphene and Intermediates Thereof
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The present invention provides processes for the preparation of zuclomiphene, as well as intermediates useful in the preparation thereof. In particular, processes are provided for the carbometallation of diphenylacetylene with a compound of Formula (3) to afford either zuclomiphene or an intermediate which is converted to zuclomiphene.
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Paragraph 0137-0138
(2021/05/21)
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- Room-Temperature Palladium(II)-Catalyzed Direct 2-Arylation of Indoles with Tetraarylstannanes
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A palladium(II)-catalyzed direct 2-arylation of indoles by tetraarylstannanes with oxygen (balloon) as the oxidant at room temperature has been developed. Various tetraarylstannanes can be employed as aryl sources for 2-arylation of indoles in up to 89% yield, providing a practical and efficient catalytic protocol for accessing 2-arylindoles.
- Liu, Yuxia,Wang, Chao,Huang, Linjuan,Xue, Dong
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supporting information
p. 1613 - 1618
(2020/09/15)
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- Nickel-Catalyzed Cross-Coupling of Functionalized Organo manganese Reagents with Aryl and Heteroaryl Halides Promoted by 4-Fluorostyrene
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A catalytic system consisting of Ni(acac) 2 (5 mol%) and 4-fluorostyrene (20 mol%) allows a convenient cross-coupling of functionalized organomanganese reagents with a variety of aryl and heteroaryl halides leading to polyfunctionalized diaryl- and arylheteroarylmethane derivatives.
- Benischke, Andreas D.,Desaintjean, Alexandre,Juli, Thomas,Cahiez, Gérard,Knochel, Paul
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supporting information
p. 5396 - 5412
(2017/12/14)
-
- Design, synthesis and antifungal activity of novel selenochroman-4-one derivatives
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A series of novel selenochroman-4-one derivatives bearing semicarbazone or nitrogen heterocycle was designed, synthesized, tested antifungal activity and characterized via 1H-NMR, 13C-NMR, and HRMS. The design of the compounds is based on the principle of molecule hybrid and bioisosterism. We aimed at attaching semicarbazones or nitrogen heterocycle to the selenochroman-4-one for enhancing antifungal activity. The antifungal activity of target compounds was evaluated using the microdilution broth method in vitro test. Bioassay results indicated that some of the derivatives displayed good fungistatic activity on Candida zeylanoides, Candida albicans, Cryptococcus neoformans, resistant to fluconazole strain 103 (Candida albicans), resistant to fluconazole strain 100 (Candida albicans) and strain SC5314 (Candida albicans). All the compounds exhibit antifungal activities against the tested funguses in different levels, among them, 7 compounds of antifungal activity against several funguses is better than that of the control drug fluconazole. Based on the results, preliminary structure activity relationships (SARs) were summarized to serve as a foundation for further investigation.
- Xu, Hang,Hu, Yu-Kun,Guo, Meng-Bi,Huang, Ai-Su,Su, Xin,Guo, Chun
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p. 2455 - 2463
(2017/10/06)
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- Nickel-Catalyzed Asymmetric Kumada Cross-Coupling of Symmetric Cyclic Sulfates
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Nickel-catalyzed enantioselective cross-couplings between symmetric cyclic sulfates and aromatic Grignard reagents are described. These reactions are effective with a broad range of substituted cyclic sulfates and deliver products with asymmetric tertiary carbon centers. Mechanistic experiments point to a stereoinvertive SN2-like oxidative addition of a nickel complex to the electrophilic substrate.
- Eno, Meredith S.,Lu, Alexander,Morken, James P.
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supporting information
p. 7824 - 7827
(2016/07/11)
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- Facile Hydrogenolysis of C(sp3)–C(sp3) σ Bonds
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The modification of benzylic quaternary, tertiary, and secondary carbon centers through palladium-catalyzed hydrogenolysis of C(sp3)–C(sp3) σ bonds is presented. When benzyl Meldrum's acid derivatives bearing quaternary benzylic centers are treated under mild hydrogenolysis conditions – palladium on carbon and atmospheric pressure of hydrogen – aromatics substituted with tertiary benzylic centers and Meldrum's acid are obtained with good to excellent yield. Analogously, substrates containing tertiary or secondary benzylic centers yield aromatics substituted with secondary benzylic centers or toluene derivatives, respectively. Furthermore, this strategy is used for the high yielding synthesis of diarylmethanes. The scope of the reductive dealkylation reaction is explored and the limitations with respect to steric and electronic factors are determined. A mechanistic analysis of the reaction is described that consisted of deuterium labelling experiments and hydrogenolysis of enantioenriched derivatives. The investigation shows that the C(sp3)–C(sp3) σ bond-cleaving events occur through a hybrid SN1/SN2 mechanism, in which the palladium center displaces a carbon-based leaving group, namely Meldrum's acid, with inversion of configuration, followed by reductive elimination of palladium to furnish a C?H bond. (Figure presented.).
- Fillion, Eric,Beaton, Eric,Nguyen, Yen,Wilsily, Ashraf,Bondarenko, Ganna,Jacq, Jér?me
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supporting information
p. 3422 - 3434
(2016/11/13)
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- Preparation method of citalopram intermediate
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The invention provides a preparation method of a citalopram intermediate, and belongs to the technical field of pharmaceuticals. In the method, 2-methyltetrahydrofuran is taken as a reaction solvent. Under the protection of nitrogen, a 4-fluorophenylmagnesium bromide solution Grignard reagent, 5-cyanophthalein and a N,N-dimethylpropyl magnesium chloride Grignard reagent are taken as raw materials. A reaction is carried out to synthesize 4-(4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrilehydrobromide. The method is characterized by high yield and high purity, and is suitable for industrial production.
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Paragraph 0053; 0054; 0055; 0056; 0057; 0058; 0066-0081
(2016/12/01)
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- Palladium-catalyzed aerobic oxidative double allylic C-H oxygenation of alkenes: A novel and straightforward route to α,β-unsaturated esters
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A mild tandem oxidative functionalization of allyl aromatic hydrocarbons was accomplished using the catalytic system of Pd(OAc)2/DMA under 1 atm O2. The green twofold C-O bond formation involving double allylic C-H oxygenation unlocks opportunities for markedly different synthetic strategies. Moreover, the reaction affords aryl α,β-unsaturated esters directly from readily available terminal olefins in moderate to good yields with excellent chemo- and stereoselectivities.
- Yang, Wanfei,Chen, Huoji,Li, Jianxiao,Li, Chunsheng,Wu, Wanqing,Jiang, Huanfeng
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supporting information
p. 9575 - 9578
(2015/06/08)
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- ENDOPEROXIDES, SYNTHESIS AND USES THEREOF FOR THE TREATMENT OF NEOPLASTIC DISEASES SUCH AS CANCER
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The present invention generally relates to processes and methods for the synthesis of endoperoxide compounds. More specifically, the invention relates to a method for preparing endoperoxide compounds starting from an aryl imine of formula (I) in the presence of a metallic catalyst and oxygen. The present invention also relates to endoperoxide compounds of formula (III) and their pharmaceutically acceptable salts thereof, useful for therapy. All substituents are defined herein. Also disclosed are methods of treating cancer using the compounds of formula (III).
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Paragraph 0187; 0186; 0205; 0206
(2014/02/15)
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- Selective introducing of aryl and amino groups: Reaction of benzanthrone and organometallic reagents
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The reaction of benzanthrone and aryl magnesium bromides produced 6-aryl-substituted benzanthrones in moderate to good yields. Similarly, 6-alkylaminobenzanthrones were selectively prepared by the reaction of benzanthrone and lithium alkylamides. In contrast, for the lithium arylamides, the arylamino groups were selectively introduced at the 4-position of the benzanthrone.
- Umeda, Rui,Namba, Teruaki,Yoshimura, Tomohiro,Nakatsukasa, Masamichi,Nishiyama, Yutaka
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p. 1526 - 1531
(2013/02/23)
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- Novel tetranuclear triarylantimony(v) complexes with (±)-mandelic acid ligands: Synthesis, characterization, in vitro cytotoxicity and DNA binding properties
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Four novel tetranuclear organoantimony(v) complexes [R3SbL] 4, in which LH = (±)-mandelic acid and R = phenyl (1), 4-fluorophenyl (2), 3-fluorophenyl (3), 3,4,5-trifluorophenyl (4), were synthesized and characterized. The complexes displayed rapid, low micromolar in vitro cytotoxicity against a range of epithelial tumour cells and efficient CT-DNA binding.
- Jiang, Jin,Yin, Handong,Wang, Fangli,Han, Zhong,Wang, Fei,Cheng, Shuang,Hong, Min
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supporting information
p. 8563 - 8566
(2013/07/27)
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- Copper-catalyzed difluoromethylation of β,γ-unsaturated carboxylic acids: An efficient allylic difluoromethylation
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Not one but two! A new strategy for the regiospecific construction of compounds with allylic CF2H groups has been developed. The decarboxylative (phenylsulfonyl)difluoromethylation of β,γ- unsaturated carboxylic acids is catalyzed by a Lewis acid (CuCl 2·2 H2O), and the resulting product easily undergoes desulfonylation. Copyright
- He, Zhengbiao,Hu, Mingyou,Luo, Tao,Li, Lingchun,Hu, Jinbo
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supporting information
p. 11545 - 11547
(2013/01/15)
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- IMPROVED PROCESS FOR THE PREPARATION OF EZETIMIBE
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The present invention provides an improved process for the preparation of compound of Formula II, which is a key intermediate for the preparation of Ezetimibe, through stereoselective addition of an organometallic reagent to novel aldehyde intermediates under chiral catalysis.
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Page/Page column 11
(2012/12/13)
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- Preparation of Escitalopram, Its Salts and Intermediates
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The present patent application relates to an improved process for the preparation of escitalopram, its salts and intermediates. It also relates to a novel crystalline form S of citalopram diol intermediate, process for preparation and its use in the preparation of citalopram, escitalopram and their salts.
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Page/Page column 6
(2011/05/03)
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- PREPARATION OF ESCITALOPRAM, ITS SALTS AND INTERMEDIATES
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The present patent application relates to an improved process for the preparation of escitalopram, its salts and intermediates. It also relates to a novel crystalline form S of citalopram diol intermediate, process for preparation and its use in the preparation of citalopram, escitalopram and their salts.
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Page/Page column 16
(2010/04/03)
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- PROCESS FOR PREPARING EZETIMIBE USING NOVEL ALLYL INTERMEDIATES
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The present invention provides an efficient and industrially advantageous process for the preparation of ezetimibe of formula (I), using novel intermediates.
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Page/Page column 21
(2010/01/30)
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- N-(3-(IMIDAZO [1,5-A]PYRIMIDIN-4-YL)PHENYL]-SULFONAMIDES AND N-[3-(IMIDAZO[1,5-A]PYRIMIDIN-4-YL)-PHENYL]-CARBOXAMIDES AND THEIR USE AS GABAA RECEPTOR MODULATORS
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The present invention relates to compounds of formula I wherein R1, R2, R3 and X are as defined in the claims. The compounds have specific affinity for the GABAA receptor and are therefore useful in the treatment and prevention of diseases modulated by the 1 and 2-GABAA receptors.
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Page/Page column 37-38
(2008/06/13)
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- Method for the preparation of citalopram
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A method for the preparation of citalopram and its pharmaceutically acceptable salts is described; it's obtained starting from 5-cyanophthalide by reaction with a mixture of 4-fluorophenyl magnesium bromide and 3-dimethylaminopropyl magnesium chloride. The intermediate obtained is showed here-below: wherein X is an halogen, preferably chlorine or bromine, which is cyclized without any isolation.
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Page/Page column 4
(2008/06/13)
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- IMPROVED PROCESS FOR THE MANUFACTURE OF CITALOPRAM HYDROBROMIDE
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The present invention describes an improved process for the preparation of extremely pure 1-(4'-Fluorophenyl)-1-(3-dimethylaminopropyl)-5-phthalanecarbonitrile and its bromide salt (citalopram hydrobromide), which is a well known antidepressant. Other aspect of the invention are isolation of crystalline (4-Bromo-2-hydroxymethyl)phenyl-(4-fluorophenyl)-3-(dimethylaminopropyl)methanol (Bromodiol) and conversion of desmethylcitalopram which is formed during the cyanide exchange reaction, to Citalopram by heating with a mixture of formaldhyde and formic acid in chloroform. The resulting citalopram is conventionally purified using extraction methodology.
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Page/Page column 9-10
(2008/06/13)
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- ONE POT SYNTHESIS OF CITALOPRAM FROM 5-CYANOPHTHALIDE
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A process for one pot synthesis of citalopram is disclosed. The process comprises subjecting 5-cyano phthalide to Grignard reduction followed cyclization and followed by C-alkylation reaction to obtain citalopram without isolation and purification of any intermediates. In another embodiment, 5-cyano phthalide is subjected to sequential Grignard reactions followed by cyclization to obtain citalopram without isolation and purification of any intermediate stages.
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Page/Page column 8-9; 10-11
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF A CYANO-ISOBENZOFURAN
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A process for the preparation of citalopram and the pharmaceutically acceptable salts therof is disclosed by reacting 5-cyanophthalide with a 4-fluorophenyl magnesium halide, reducing the 3-hydroxymethyl-4-(4-fluoro-benzoyl)benzonitrile with an agent reducing ketones to alcohols, submitting the thus-obtained 3-hydroxymethyl-4- [(4-fluorophenyl)hydroxymethyl) benzonitrile to a cyclization reaction to give 1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile without 1,1-bis(4-fluorophenyl)-1,3-dihydro-5- isobenzofurancarbonitrile and treating 1,1-bis(4 fluorophenyl)-1,3-dihydro-5- isobenzofurancarbonitrile with a 3-(dimetylamino)propyl halide in the presence of a base.
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- Process for the preparation of citalopram
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Preparation of citalopram comprises the steps of: (a) converting the compound of Formula (I) to a compound of Formula (II), wherein R in Formula (I) represents a C2 to C5 alkylene group which may be substituted or unsubstituted, and R1 in the compounds of Formula (II) represents a carboxylic acid group or a salt or an ester thereof; and (b) converting the compound of Formula (II) to form citalopram or a pharmaceutically acceptable salt thereof, or a direct conversion of the compound of Formula (I) to citalopram
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- PROCESS FOR THE MANUFACTURE OF CITALOPRAM HYDROBROMIDE FROM 5-BROMOPHTHALIDE
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A process for the preparation of 1-(4′-fluorophenyl)-1-(3-dimethylamino-propyl)-5-phthalanecarbonitrile of formula (I), or a pharmaceutically acceptable salt thereof, comprising performing two successive Grignard reactions on 5-bromophthalide, wherein the 5-bromophthalide is reacted with the first Grignard reagent in the presence of a Lewis acid, so reducing by-product formation and improving yields.
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- Process for the production of paroxetine
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A process for the production of paroxetine is described, wherein N-substituted derivatives of 4-(p-fluorophenyl)-3-hydroxymethyl-1,2,3,6-tetrahydropyridine are treated according to the following sequence of reactions: (a) hydrogenation catalyzed by transition metal complexes with chiral diphosphinic ligands; (b) —OH derivatisation and nucleophilic substitution, the substituent being sesamol; (c) N-dealkylation. The process is highly stereospecific and brings about the formation of intermediates enriched with the desired isomeric components, which are converted into paroxetine in quantitative yields.
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- Preparation, characterization and properties of dipolar 1,2-N,N-dimethylaminomethylferrocenylsilanes
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A series of substituted 1,2-N,N-dimethylaminomethlyferrocenyl compounds were synthesized and characterized by 1H-NMR, 13C-NMR, 29Si-NMR, ES-MS, IR, UV - vis and 57Fe-M?ssbauer spectroscopy. The new (R,S)-2-(N,N-dimethylaminomethyl)ferrocenyl-(arly)silanes (R,S)-FcNSiMen(C6H4X)m (n = 2-0, m = 1, X = p-F (5); m = 2, X = p-F (6); m = 3, X = p-F (7) and m = 1, X = p-Br (14) were formed by the reaction of 2-dimethylaminomethylferrocenyllithium FcNLi (1) with chloroarylsilanes ClSi(Me)n (C6H4X)m (n = 2-0, m = 1, X = p-F (2); m = 2, X = p-F (3); m = 3, X = p-F (4) and m = 1, X = p-Br (13)). The treatment of 5, 6 and 14 with gaseous hydrogen chloride or picric acid resulted in the formation of the hydrochloride complexes 9, 10, 15 and the picrates 11, 12 and 16. The treatment of 14 with LiR or Mg and DMF resulted in the formation of (R,S)-2-(N,N-dimethylaminomethyl)ferrocenyl(4-formylphenyl)dimethylsilane (18). The crystal structures of 7, 12 and 15 were determined by single crystal X-ray analyses. 57Fe-M?ssbauer spectroscopy gives evidence of a significant electronic coupling between the ferrocenyl unit and the organic acceptor moiety of the molecules in the ground state.
- Beyer, Christian,B?hme, Uwe,Pietzsch, Claus,Roewer, Gerhard
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p. 187 - 201
(2007/10/03)
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- Method for the preparation of citalopram
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A method for the preparation of citalopram is described comprising reaction of a compound of Formula (IV) wherein R1is H or C1-6alkylcarbonyl successively with a Grignard reagent of 4-halogen-fluorophenyl and a Grignard reagent of 3-halogen-N,N-dimethylpropylamine, effecting ring closure of the resulting compound of Formula (IV) and converting the resulting 1,3-dihydroisobenzofuran compound to the corresponding 5-cyano derivative, i.e. citalopram.
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- Triazole derivatives
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The present invention relates to a novel glycerol derivative and a process for preparing the same, and a process for preparing a triazole derivative. According to the present invention, an optical active 2-arylglycerol derivative which is a novel and useful as a synthetic intermediate of medicament can be provided and furthermore, (R)-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazole-1-yl)-propane-1,2-diol which is useful as an antifungal agent can be prepared.
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- Fungicidal use of phenolic aromatic compounds
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A plant fungicide method comprises applying to the locus of a plant pathogen a fungicidally effective amount of a compound of formula (I) STR1 or a salt or a complex thereof, wherein: R1, R2, R3, R4, R5, R6, R7, and R8 are independently H, halo, NO2, (C1 -C4) alkyl, or halo(C1 -C4) alkyl; R3', R4', R5', R3", R4", and R5" are independently H, halo, OH, or CH3, provided that at least one is OH; R6 ' and R6 " are independently H or OH.
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- PHOSPHORUS-CONTAINING HMG-COA REDUCTASE INHIBITORS, NEW INTERMEDIATES AND METHOD
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Compounds which are useful as inhibitors of cholesterol biosynthesis and thus as hypocholesteroleumic agents are provided which have the structure STR1 wherein R is OH, or salts thereof or lower alkoxy; R. sup.x is H or alkyl;X is--CH 2--,--
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- Fluorine-substituted cyclohexylcyclohexene derivative
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A compound represented by formula (I): STR1 wherein R represents a straight chain alkyl group having from 1 to 9 carbon atoms; STR2 represents STR3 represents a hydrogen atom or a fluorine atom; and STR4 has a trans (equatorial-equatorial) configuration, is disclosed. The compound of formula (I) exhibits a nematic phase in the vicinity of room temperature or in a temperature range higher than room temperature and has a small optical anisotropy and a positive dielectric anisotropy and is, therefore, useful in preparing a liquid crystal display cell excellent in viewing-angle characteristics.
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- Antimycotic 1,1-disubstituted cyclopropane derivatives
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Compounds I STR1 where A equals t-butyl, phenyl, biphenylyl, phenoxyphenyl, benzylphenyl, benzyloxyphenyl, phenylthiophenyl, phenylsulfinylphenyl, phenylsulfonylphenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, indanyl, fluorenyl, thienyl, furyl, pyridyl, isoxazolyl, pyrazolyl, benzofuryl or benzothienyl, Z equals CO, CH2 or radicals of ketone derivatives; Y equals azole or equals --X--R8 (R8 =(cyclo)alkyl or an aromatic) or equals a number of amine derivatives or equal acyl, are antimycotics. The preparation and use as medicaments are described.
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- Substituted pyranone inhibitors of cholesterol synthesis
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The methyl, ethyl, n-propy, 2-(acetylamino)ethyl, or 1-(2,3-dihydroxy)propyl ester of E-(3R,5S)-7-(4'-fluoro-3,3',5-trimethyl[1,1'-biphenyl]-2-yl)-3,5-dihydroxy-6-heptenoic acid of structural formula: STR1 are HMG-CoA reductase inhibitors useful in the treatment of conditions associated with hypercholesterolemia.
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- Process for the production of acyloins
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Process for the production of an acyloin comprising the steps of: A. reacting a Grignard reagent with silylated cyanohydrin, B. treating the reaction product of step A with aqueous acid, and C. recovering the resulting acyloin. Acyloins thus formed are useful as photoinitiators for initiation of free radical polymerization reactions.
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- Substituted pyranone inhibitors of cholesterol synthesis
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6-Phenyl-, phenylalkyl- and phenylethenyl-4-hydroxytetrahydropyran-2-ones in the 4(R)-trans stereoisomeric forms are potent inhibitors of cholesterol synthesis by virtue of their ability to inhibit the enzyme, 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
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- SUBSTITUTED PYRANONE INHIBITORS OF CHOLESTEROL SYNTHESIS
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6-Phenyl-, phenylalkyl-and phenylethenyl-4-hydroxytetrahydropyran-2-ones in the 4(R)-trans stereoisomeric forms are potent inhibitors of cholesterol synthesis by virtue of their ability to inhibit the enzyme, 3-hydroxy-3-methylglutaryl-coenzyme A reductas
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- Substituted biphenyl-2-carboxaldehydes
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Substituted biphenyl-2-carboxaldehydes are prepared in good yield by reacting palladium complexes of substituted benzaldehyde aniline Schiff bases with substituted phenylmagnesium bromides in the presence of at least six, preferably eight, molar equivalents of triphenylphosphine.
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- Cis/trans isomerization of 6-(substituted-aryl-ethenyl)-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-ones
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Biologically inactive cis-6-(substituted-arylethenyl)-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-ones are isomerized to the corresponding anti-hypercholesterolemic trans-isomers by heating in the presence of a heavy metal salt.
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