- Access to Trisubstituted Fluoroalkenes by Ruthenium-Catalyzed Cross-Metathesis
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Although the olefin metathesis reaction is a well-known and powerful strategy to get alkenes, this reaction remained highly challenging with fluororalkenes, especially the Cross-Metathesis (CM) process. Our thought was to find an easy accessible, convenient, reactive and post-functionalizable source of fluoroalkene, that we found as the methyl 2-fluoroacrylate. We reported herein the efficient ruthenium-catalyzed CM reaction of various terminal and internal alkenes with methyl 2-fluoroacrylate giving access, for the first time, to trisubstituted fluoroalkenes stereoselectively. Unprecedent TON for CM involving fluoroalkene, up to 175, have been obtained and the reaction proved to be tolerant and effective with a large range of olefin partners giving fair to high yields in metathesis products. (Figure presented.).
- Nouaille, Augustin,Pannecoucke, Xavier,Poisson, Thomas,Couve-Bonnaire, Samuel
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supporting information
p. 2140 - 2147
(2021/03/06)
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- Efficient One-Pot Reductive Aminations of Carbonyl Compounds with Aquivion-Fe as a Recyclable Catalyst and Sodium Borohydride
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A one-pot reductive amination of aldehydes and ketones with NaBH4 was developed with a view to providing efficient, economical and greener synthetic conditions. A recyclable iron-based Lewis catalyst, Aquivion-Fe, was used to promote imine formation in cyclopentyl methyl ether, followed by the addition of a small amount of methanol to the reaction mixture to enable C=N reduction by NaBH4. The protocol, applied to a wide number of amines and carbonyl compounds, resulted in ever complete conversion of these latter with excellent chemoselectivity towards the expected amination products in the most cases. Isolated yields, determined for a selection of the screened substrates, were found consistent with the previously obtained conversion and selectivity data. Cinacalcet, an important active pharmaceutical ingredient, was efficiently prepared by the title procedure.
- Airoldi, Veronica,Piccolo, Oreste,Roda, Gabriella,Appiani, Rebecca,Bavo, Francesco,Tassini, Riccardo,Paganelli, Stefano,Arnoldi, Sebastiano,Pallavicini, Marco,Bolchi, Cristiano
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supporting information
p. 162 - 168
(2019/12/11)
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- Three-Component, Interrupted Radical Heck/Allylic Substitution Cascade Involving Unactivated Alkyl Bromides
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Developing efficient and selective strategies to approach complex architectures containing (multi)stereogenic centers has been a long-standing synthetic challenge in both academia and industry. Catalytic cascade reactions represent a powerful means of rapidly leveraging molecular complexity from simple feedstocks. Unfortunately, carrying out cascade Heck-type reactions involving unactivated (tertiary) alkyl halides remains an unmet challenge owing to unavoidable β-hydride elimination. Herein, we show that a modular, practical, and general palladium-catalyzed, radical three-component coupling can indeed overcome the aforementioned limitations through an interrupted Heck/allylic substitution sequence mediated by visible light. Selective 1,4-difunctionalization of unactivated 1,3-dienes, such as butadiene, has been achieved by employing different commercially available nitrogen-, oxygen-, sulfur-, or carbon-based nucleophiles and unactivated alkyl bromides (>130 examples, mostly >95:5 E/Z, >20:1 rr). Sequential C(sp3)-C(sp3) and C-X (N, O, S) bonds have been constructed efficiently with a broad scope and high functional group tolerance. The flexibility and versatility of the strategy have been illustrated in a gram-scale reaction and streamlined syntheses of complex ether, sulfone, and tertiary amine products, some of which would be difficult to access via currently established methods.
- Bellotti, Peter,Glorius, Frank,Heidrich, Bastian,Huang, Huan-Ming,Pflüger, Philipp M.,Schwarz, J. Luca
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supporting information
p. 10173 - 10183
(2020/06/27)
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- Method for reducing carboxylic acid into aldehyde compounds
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The invention discloses a method for reducing carboxylic acid into aldehyde compounds, and belongs to the field of organic chemical synthesis. Specifically, in an argon atmosphere, a carboxylic acid compound, a transition metal nickel compound, an anhydride compound, a ligand and a reducing agent are dissolved in an organic solvent, the mixture is heated and subjected to stirring reaction, after the reaction is finished, the pressure is reduced to remove the organic solvent, column chromatography separation is performed, and various aldehyde compounds are obtained. The method has the advantages of simple synthesis steps, mild reaction conditions, simplicity and easiness in operation, realization of successful reduction of the carboxylic acid compound into the aldehyde organic compounds, small use amount of the reaction catalyst, high product yield, and provision of a new approach for reduction of the carboxylic acid compound into the aldehyde compounds. Compared with a conventional method, the method has the advantages that raw materials are cheap, easy to obtain and environmentally friendly, substrate universality and functional group compatibility are improved, and the method hascertain innovativeness and unique research significance in organic synthesis methodology.
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Paragraph 0039-0042
(2020/02/27)
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- Carbene-Catalyzed α-Carbon Amination of Chloroaldehydes for Enantioselective Access to Dihydroquinoxaline Derivatives
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An NHC-catalyzed α-carbon amination of chloroaldehydes was developed. Cyclohexadiene-1,2-diimines are used as amination reagents and four-atom synthons. Our reaction affords optically enriched dihydroquinoxalines that are core structures in natural products and synthetic bioactive molecules.
- Huang, Ruoyan,Chen, Xingkuan,Mou, Chengli,Luo, Guoyong,Li, Yongjia,Li, Xiangyang,Xue, Wei,Jin, Zhichao,Chi, Yonggui Robin
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supporting information
p. 4340 - 4344
(2019/06/14)
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- Copper(i)-catalysed stereoselective debromoborylation of aliphatic 1,1-dibromo-1-alkenes with bis(pinacolato)diboron
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A stereoselective debromoborylation of aliphatic 1,1-dibromo-1-alkenes to prepare (Z)-1-bromo-1-alkenylboronate esters using copper(i) catalysts was developed. The debromoborylation of various aliphatic 1,1-dibromo-1-alkenes in the presence of a copper(i) catalyst and bis(pinacolato)diboron proceeded smoothly to produce (Z)-1-bromo-1-alkenylboronate esters in good yields with only Z geometry.
- Pang, Yadong,Kojima, Ryoto,Ito, Hajime
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supporting information
p. 6187 - 6190
(2018/09/10)
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- Preparation method for m-trifluoromethylphenol benzenepropanal
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The invention relates to a preparation method for m-trifluoromethylphenol benzenepropanal. The preparation method for the m-trifluoromethylphenol benzenepropanal mainly solves the problems in the prior art that the conversion rate of the m-trifluoromethylphenol styrene is low, and the selectivity of the m-trifluoromethylphenol benzenepropanal is low and comprises the step that the m-trifluoromethylphenol styrene and hydrogen react with a carbon monoxide material and a catalyst composition to obtain the m-trifluoromethylphenol benzenepropanal, wherein the catalyst composition comprises a rhodium complex and a dicyclopentadienyl high valent metal cation diphosphine compound, the technical problems are better solved, and the preparation method can be applied to industrial production of the m-trifluoromethylphenol benzenepropanal.
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Paragraph 0036-0104
(2019/01/14)
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- Synthesis and in vitro antiproliferative activity of C5-benzyl substituted 2-amino-pyrrolo[2,3-d]pyrimidines as potent Hsp90 inhibitors
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A novel series of heat shock protein 90 (Hsp90) inhibitors was identified by X-ray crystal analysis of complex structures at solvent-exposed exit pocket C. The 2-amino-pyrrolo[2,3-d]pyrimidine derivatives, 7-deazapurines substituted with a benzyl moiety at C5, showed potent Hsp90 inhibition and broad-spectrum antiproliferative activity against NCI-60 cancer cell lines. The most potent compound, 6a, inhibited Hsp90 with an IC50of 36?nM and showed a submicromolar mean GI50value against NCI-60 cell lines. The interaction of 6a at the ATP-binding pocket of Hsp90 was confirmed by X-ray crystallography and Western blot analysis.
- Lee, Ju-Hyeon,Shin, Sang Chul,Seo, Seon Hee,Seo, Young Ho,Jeong, Nakcheol,Kim, Chan-Wha,Kim, Eunice EunKyeong,Keum, Gyochang
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supporting information
p. 237 - 241
(2016/12/27)
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- Switchable Site-Selective Catalytic Carboxylation of Allylic Alcohols with CO2
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A switchable site-selective catalytic carboxylation of allylic alcohols has been developed in which CO2 is used with dual roles, both facilitating C?OH cleavage and as a C1 source. This protocol is characterized by its mild reaction conditions, absence of stoichiometric amounts of organometallic reagents, broad scope, and exquisite regiodivergency which can be modulated by the type of ligand employed.
- van Gemmeren, Manuel,B?rjesson, Marino,Tortajada, Andreu,Sun, Shang-Zheng,Okura, Keisho,Martin, Ruben
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supporting information
p. 6558 - 6562
(2017/05/29)
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- Novel pyrrolo pyrimidine derivatives and composition for preventing or treating cancer comprising the same
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The present invention relates to a novel pyrrolo pyrimidine compound represented by chemical formula 1, pharmaceutically acceptable salt or hydrate thereof, a manufacturing method thereof, and a pharmaceutical composition comprising the compound for preventing or treating cancer. In chemical formula 1, R^1, R^2, R^3, R^4, R^5, and X are the same as defined in the specification.COPYRIGHT KIPO 2016
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Paragraph 0113; 0222; 0223; 0224; 0225
(2016/11/24)
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- A PROCESS FOR THE PREPARATION OF CINACALCET HYDROCHLORIDE AND ITS INTERMEDIATE
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This invention relates to a process for the preparation of cinacalcet hydrochloride and its key intermediate 3-[3-(trifluoromethyl) phenyl]propionaldehyde, said process comprising reductive amination of 3-[3-(trifluoromethyl)phenyl]propionaldehyde and (R)-(1-napthylethylamine) in presence of activated sodium borohydride by an acid; the invention also provides a process for preparing 3- [3-(trifluoromethyl)phenyl]propionaldehyde by reacting 3-[3- (trifluoromethyl)phenyl]propan-1-ol (IV) with dimethylsulfide and N-chlorosuccinamide; or dimethylsulfide and N-bromosuccinamide; or dimethylsulfide and chlorine gas; or thioanisole and N-chlorosuccinamide; or thioanisole and N-bromosuccinamide in a suitable organic solvent.
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Page/Page column 6-7
(2014/02/16)
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- Industrially viable synthesis of 3-[3-(trifluoromethyl)phenyl] propionaldehyde. A key intermediate of cinacalcet
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An improved synthesis of 3-[3-(trifluoromethyl)phenyl]propionaldehyde (2), a key intermediate of cinacalcet hydrochloride ((R)-alpha-methyl-N-[3-[3- (triflouoromethyl)phenyl]propyl]-1-naphthalene methane amine hydrochloride) has been described. The key step include the Corey-Kim oxidation under normal conditions.
- Chavakula, Ramadas,Mutyala, Narayana Rao,Chennupati, Srinivasa Rao
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p. 1259 - 1261
(2013/11/06)
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- PROCESS FOR CINACALCET HYDROCHLORIDE
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3-[3-(Trifluoromethyl)phenyl]propionaldehyde is a key intermediate for the preparation of cinacalcet hydrochloride. The present invention provides a novel process for the preparation of 3-[3-(trifluoromethyl)phenyl]propionaldehyde. The present invention also provides an improved process for preparation of cinacalcet hydrochloride in high yields. The present invention further provides a process for purification of cinacalcet hydrochloride.
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Page/Page column 12
(2012/02/02)
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- 5,6,7,8-TETRAHYDRO-IMIDAZO[1,5-A]PYRAZINE COMPOUNDS
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The invention relates to 5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine derivatives of formula (I) wherein R1, R2, R3, and R4 are as described n the description, to salts, especially pharmaceutically acceptable salts thereof, and to the use of such compounds as medicaments; especially as orexin receptor antagonists.
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Page/Page column 20; 21
(2011/05/08)
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- PYRAZOLO-TETRAHYDROPYRIDINE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS
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The invention relates to novel pyrazolo-tetrahydropyridines compounds and their use as orexin receptor antagonists.
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Page/Page column 23
(2011/02/18)
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- PROMOTER FOR BICARBONATE SECRETION IN GASTROINTESTINAL TRACT
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Disclosed is a substance which can prevent or treat a disease associated with the secretion of an acid. A calcium receptor activator is used as an active ingredient of a promoter for the bicarbonate secretion in a gastrointestinal tract. Examples of the calcium receptor activator include γ-Glu-X-Gly [wherein X represents an amino acid or an amino acid derivative], γ-Glu-Val-Y [wherein Y represents an amino acid or an amino acid derivative], γ-Glu-Ala, γ-Glu-Gly, γ-Glu-Cys, γ-Glu-Met, γ-Glu-Thr, γ-Glu-Val, γ-Glu-Orn, Asp-Gly, Cys-Gly, Cys-Met, Glu-Cys, Gly-Cys, Leu-Asp, γ-Glu-Met(O), γ-Glu-y-Glu-Val, γ-Glu-Val-NH2, γ-Glu-Val-ol, γ-Glu-Ser, γ-Glu-Tau, γ-Glu-Cys(S-Me)(O), γ-Glu-Leu, γ-Glu-Ile, γ-Glu-t-Leu and γ-Glu-Cys(S-Me).
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- A process for the preparation of cinacalcet and intermediates thereof
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The present invention relates to a process for the preparation of (R)-(1-Naphthalen-1-yl-ethyl)-[3-(3-trifluoromethyl-phenyl)-propyl]-amine or a salt thereof, in particular the hydrochloride, and intermediates useful in its synthesis.
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Page/Page column 6
(2011/06/23)
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- PROCESS FOR THE PREPARATION OF CINACALCET AND INTERMEDIATES THEREOF
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The present invention relates to a process for the preparation of (R)-(1-Naphthalen-1-yl-ethyl)-[3-(3-trifluoromethyl-phenyl)-propyl]-amine or a salt thereof, in particular the hydrochloride, and intermediates useful in its synthesis.
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Page/Page column 3-4
(2011/06/19)
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- IMMUNOSTIMULATING AGENT
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Disclosed is an immunostimulating agent which can stimulate immunity effectively. The immunostimulating agent comprises, as an active ingredient, a calcium receptor activator such as γ-Glu-X-Gly [wherein X represents an amino acid or a derivative thereof other than Cys], γ-Glu-Val-Y [wherein Y represents an amino acid or a derivative thereof], γ-Glu-Ala, γ-Glu-Gly, γ-Glu-Met, γ-Glu-Thr, γ-Glu-Val, γ-Glu-Orn, Asp-Gly, Cys-Gly, Cys-Met, Glu-Cys, Gly-Cys, Leu-Asp, γ-Glu-Met(O), γ-Glu-y-Glu-Val, γ-Glu-Val-NH2, γ-Glu-Val-ol, γ-Glu-Ser, γ-Glu-Tau, γ-Glu-Cys(S-Me)(O), γ-Glu-Leu, γ-Glu-Ile, γ-Glu-t-Leu, γ-Glu-Cys(S-Me), a cation having a valency of 2 or more, protamine, polylysine, spermine, spermidine, putrescine, cinacalcet, a cinacalcet analogue compound, and a salt of any one of the aforementioned components.
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- PROCESSES FOR PREPARING INTERMEDIATE COMPOUNDS USEFUL FOR THE PREPARATION OF CINACALCET
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The invention relates, in general, to an improved process for preparing compounds (e.g., 3-(3-trifluoromethylphenyl)propanal (Compound III, below)), which are key intermediates for the synthesis of cinacalcet, its salts and/or solvates thereof, as well as the use of such compounds prepared by such process for the preparation of cinacalcet and/or its salts or solvates.
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Page/Page column 3
(2010/11/03)
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- 5,6,7,8-TETRAHYDRO-IMIDAZO[1,5-A]PYRAZINE COMPOUNDS
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The invention relates to 5,6,7,8-tetrahydro-imidazo[1,5- a]pyrazine derivatives of formula (I) wherein R1, R2, R3, and R4 are as described n the description, to salts, especially pharmaceutically acceptable salts thereof, and to the use of such compounds as medicaments; especially as orexin receptor antagonists.
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Page/Page column 45
(2010/01/30)
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- PYRAZOLO-TETRAHYDRO PYRIDINE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS
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The invention relates to novel pyrazolo-tetrahydropyridines compounds and their use as orexin receptor antagonists.
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Page/Page column 11; 18
(2009/04/24)
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- Novel and potent inhibitors of stearoyl-CoA desaturase-1. Part I: Discovery of 3-(2-hydroxyethoxy)-4-methoxy-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide
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A series of structurally novel stearoyl-CoA desaturase-1 (SCD-1) inhibitors has been identified by optimizing a hit from our corporate library. Preliminary structure-activity relationship (SAR) studies led to the discovery of the highly potent and orally bioavailable thiazole-based SCD-1 inhibitor, 3-(2-hydroxyethoxy)-4-methoxy-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide (23a).
- Uto, Yoshikazu,Ogata, Tsuneaki,Harada, Jun,Kiyotsuka, Yohei,Ueno, Yuko,Miyazawa, Yuriko,Kurata, Hitoshi,Deguchi, Tsuneo,Watanabe, Nobuaki,Takagi, Toshiyuki,Wakimoto, Satoko,Okuyama, Ryo,Abe, Manabu,Kurikawa, Nobuya,Kawamura, Sayako,Yamato, Michiko,Osumi, Jun
-
experimental part
p. 4151 - 4158
(2010/04/29)
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- Mechanistic analysis of the photocycloaddition of silyl-tethered alkenes
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(Chemical Equation Presented) The photochemistry of substituted cinnamyloxy silanes has been examined in both cyclohexane and acetonitrile solvents. Alkene isomerization occurs in addition to cycloaddition. Fluorescence quantum yields and excited singlet state lifetimes have been determined for each compound. We have used the information in order to better understand the regio- and stereoselectivity of photocycloaddition between silyl-tethered cinnamyl groups. This study allows us to conclude that the 2 + 2 photocycloaddition between alkenes is not a Woodward-Hoffmann orbital symmetry controlled event. The most consistent explanation for the excellent regio- and stereoselectivity is that the photocycloaddition is conformationally controlled.
- Fleming, Steven A.,Parent, Alexander A.,Parent, Ephraim E.,Pincock, James A.,Renault, Lise
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p. 9464 - 9470
(2008/03/14)
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- PROCESS FOR PREPARING CINACALCET HYDROCHLORIDE
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Processes for preparing cinacalcet are provided.
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Page/Page column 27
(2008/06/13)
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- Synthesis of Cinacalcet congeners
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Two related substances 1 and 2 of Cinacalet were prepared. Two racemic isomeric dihydronaphthalenes 1 and 2 were prepared from commercially available 5-hydroxytetralone in five linear steps. A key palladium-catalyzed double bond migration led to the synthesis of both isomers from the same starting material. Preparative chiral HPLC separation provided the enantiomerically pure materials. An asymmetric synthesis employing CBS reduction to furnish 1 was also developed.
- Wang, Xin,Chen, Ying,Crockett, Richard,Briones, Jorge,Yan, Tony,Orihuela, Carlos,Zhi, Benxin,Ng, John
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p. 8355 - 8358
(2007/10/03)
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