- An improved and large scale synthesis of the natural coumarin scopoletin
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Isovanillin was oxidized with magnesium monoperoxyphthalate to 4-methoxyresorcinol (2) and the latter was reacted with 3-oxo-propionic acid ethylester prepared in situ to give scopoletin (1). These reactions can be achieved in kg scale in high yields.
- Hauer,Ritter,Grotemeier
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Read Online
- PYRAZOLO[1,5-a]PYRIMIDIN-7(4H)-ONE INHIBITORS OF DYNEIN
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Pyrazolo[1,5-a]pyrimidin-7(4H)-ones of formula (I) inhibit intraflagellar transport and are useful as anticancer agents and as probes of the function of dynein-dependent systems.
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Paragraph 0043; 0095; 0099
(2021/07/17)
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- α-Amino Acid-Isosteric α-Amino Tetrazoles
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The synthesis of all 20 common natural proteinogenic and 4 otherα-amino acid-isosteric α-amino tetrazoles has been accomplished, whereby the carboxyl group is replaced by the isosteric 5-tetrazolyl group. The short process involves the use of the key Ugi tetrazole reaction followed by deprotection chemistries. The tetrazole group is bioisosteric to the carboxylic acid and is widely used in medicinal chemistry and drug design. Surprisingly, several of the common α-amino acid-isosteric α-amino tetrazoles are unknown up to now. Therefore a rapid synthetic access to this compound class and non-natural derivatives is of high interest to advance the field.
- Zhao, Ting,Kurpiewska, Katarzyna,Kalinowska-T?us?cik, Justyna,Herdtweck, Eberhardt,D?mling, Alexander
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supporting information
p. 3009 - 3018
(2016/03/26)
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- 2-(1-HETEROARYLPIPERAZIN-4-YL)METHYL-1,4-BENZODIOXANE DERIVATIVES AS ALPHA2C ANTAGONISTS
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Compounds of formula I (formula I), wherein A is an optionally substituted five-membered unsaturated heterocyclic ring containing 1, 2 or 3 N, O or S ring heteroatom(s) exhibit alpha2C antagonistic activity and are thus useful for the treatment of diseases or conditions of the peripheric or central nervous system.
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Page/Page column 24
(2016/12/22)
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- Preparation method of 3-N,N-dimethylamino ethyl acrylate
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The present invention provides a preparation method of 3-N,N-dimethylamino ethyl acrylate. According to the method, a 3-N,N-dimethylamino ethyl acrylate crude product and a polymerization inhibitor are mixed and subjected to reduced pressure distillation, and 3-N,N-dimethylamino ethyl acrylate is obtained; the polymerization inhibitor in use is composed two or more of 2,6-binitro p-cresol, o-sec-4,6-dinitrophenol, 2, 4-dimethyl-6-tertiary butyl phenol, 2,6-binitro-p-cresol, 2,2,6,6-tetramethylpiperidine nitric oxide, 2,2,6,6-tetramethyl-4-piperidone, N-methyl-2-pyrrolidone, dimethyl-thioltoluenediamine and an organic sulfonic acid compound. The specific polymerization inhibitor and the 3-N,N-dimethylamino ethyl acrylate crude product are selected and mixed to be subjected to reduced pressure distillation, the purity of 3-N,N-dimethylamino ethyl acrylate obtained through distillation is high, and the yield is also high.
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Paragraph 0038
(2016/10/08)
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- Studies towards the synthesis of secoiridoids
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A new approach to secoiridoids, based on the synthesis of the key functionalized intermediates 4 and 5, is presented. These compounds were tested in formal [3+3] cycloadditions. Acyl-chloride 15 was transformed into enol α,β-unsaturated ester 16, which was involved in a N-heterocyclic carbene rearrangement to give an advanced precursor 17 in the total synthesis of secoiridoids.
- Wu, Shaoping,Zhang, Yongmin,Agarwal, Jyoti,Mathieu, Emilie,Thorimbert, Serge,Dechoux, Luc
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supporting information
p. 7663 - 7669
(2015/09/07)
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- An efficient procedure for the synthesis of formylacetic esters
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An efficient synthesis of formylacetic esters via ozonolysis of trans-β-hydromuconic esters followed by a solid-supported triphenylphosphine reduction has been developed. In addition, an extension toward formylacetic amides and a one-pot preparation of more stable intermediates which can be used for further transformations are also described.
- Edvinsson, Sofie,Johansson, Susanne,Larsson, Andreas
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p. 6819 - 6821
(2013/01/15)
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- New [11C]phosgene based synthesis of [11C]pyrimidines for positron emission tomography
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Thymine, 5-FU, and uracil were successfully synthesized through a procedure involving a cyclocondensation of triphosgene with newly developed (α-substituted β-aminoacrylamides intermediates (1a, X= Me; 1b, X= F; 1c, X= H). The radioligands [2-11C]thymine and [2- 11C]5-fluorouracil were synthesized in high radiochemical yields in 16-17 minutes from the end of bombardment by applying the cyclocondensation method with [11C]COCl2.
- Seki, Koh-Ichi,Nishijima, Ken-Ichi,Sanoki, Kimihito,Kuge, Yuji,Takahashi, Masayuki,Akizawa, Hiromichi,Tamaki, Nagara,Wiebe, Leonard I.,Ohkura, Kazue
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experimental part
p. 1307 - 1321
(2010/10/03)
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- PYRIDINYL-PYRIMIDINE DERIVATIVES USEFUL AS POTASSIUM CHANNEL MODULATING AGENTS
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This invention relates to novel pyridinyl-pyrimidine derivatives and their use as potassium channel modulating agents. Moreover the invention is directed to pharmaceutical compositions useful for the treatment or alleviation of diseases or disorders associated with the activity of potassium channels.
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Page/Page column 17
(2008/06/13)
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- METHOD FOR SYNTHESIS OF KETO ACID OR AMINO ACID BY HYDRATION OF ACETHYLENE COMPOUND
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An object of the present invention is to provide a method for synthesis of keto acids by hydration of an acetylene compound (acetylene-carboxylic acids) under mild conditions free from harmful mercury catalysts and a method for synthesis of amino acids from acetylene-carboxylic acids in a single container (one-pot or tandem synthesis). In one embodiment of the method according to the present invention for synthesis of keto acids, acetylene-carboxylic acids is hydrated in the presence of a metal salt represented by General Formula (1), where M1 represents an element in Group VIII, IX, or X of the periodic table, and X1, X2, or X3 ligand represents halogen, H2O, or a solvent molecule, and k represents a valence of a cation species, and Y represents an anion species, and L represents a valence of the anion species, and each of K and L independently represents 1 or 2, and k × m = L × n.
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Page/Page column 22; 23
(2008/12/06)
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- 1,2,3-Thiadiazole substituted pyrazolones as potent KDR/VEGFR-2 kinase inhibitors
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KDR kinase inhibition is considered to play an important role in regulating angiogenesis, which is vital for the survival and proliferation of tumor cells. Recently we disclosed a structure-based kinase inhibitor design strategy which led to the identification of a new class of VEGFR-2/KDR kinase inhibitors bearing heterocyclic substituted pyrazolones as the core template. Instability in a rat S9 preparation and poor iv PK profiles for most of these inhibitors necessitated exploration of new pyrazolones to identify new analogs with improved metabolic stability. Optimization of the heterocyclic moiety led to the identification of the thiadiazole series of pyrazolones (D) as potent VEGFR-2/KDR kinase inhibitors. SAR modifications, kinase selectivity profiling, and structural elements for improved PK properties were explored. Oral bioavailability up to 29% was achieved in the rat. Modeling results based on the Glide XP docking approach supported our postulation regarding the interaction of the lactam segment of the pyrazolones with the hinge region of the KDR kinase.
- Tripathy, Rabindranath,Ghose, Arup,Singh, Jasbir,Bacon, Edward R.,Angeles, Thelma S.,Yang, Shi X.,Albom, Mark S.,Aimone, Lisa D.,Herman, Joseph L.,Mallamo, John P.
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p. 1793 - 1798
(2007/10/03)
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- The hydroxyl radical reaction rate constant and products of ethyl 3-ethoxypropionate
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The relative rate technique has been used to measure the hydroxyl radical (OH) reaction rate constant of ethyl 3-ethoxypropionate (EEP, CH3CH2-O-CH2CH2C(O)O-CH 2CH3). EEP reacts with OH with a bimolecular rate constant of (22.9 ± 7.4) × 10-12 cm3 molecule-1 s-1 at 297 ± 3 K and l atmosphere total pressure. In order to more clearly define EEP's atmospheric reaction mechanism, an investigation into the OH + EEP reaction products was also conducted. The OH + EEP reaction products and yields observed were: ethyl glyoxate (EG, 25 ± 1% HC(=O)C(=O)-O-CH2CH3), ethyl (2-formyl) acetate (EFA, 4.8 ± 0.2%, HC(=O)-CH2-C(=O)-O-CH2CH3), ethyl (3-formyloxy) propionate (EFP, 30 ± 1%, HC(=O)-O-CH2CH2-C(=O)-O-CH2CH3), ethyl formate (EF, 37 ± 1%, HC(=O)O-CH2CH3), and acetaldehyde (4.9 ± 0.2%, HC(=O)CH3). Neither the EEP's OH rate constant nor the OH/EEP reaction products have been previously reported. The products' formation pathways are discussed in light of current understanding of oxygenated hydrocarbon atmospheric chemistry.
- Steven Baxley,Henley, Michael V.,Wells
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p. 637 - 644
(2007/10/03)
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- A simple total synthesis of naturally occurring hydroxy-amino acids by enzymatic kinetic resolution
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Both optically pure enantiomers of GABOB and isoserine were obtained by enzymatic kinetic resolution of acetylated precursors in three or four steps. The key intermediates were cyanohydrins available from simple aldehydes. This procedure can be applied to other unusual hydroxy amino acids widely distributed in biologically important peptides.
- Lu,Miet,Kunesch,Poisson
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p. 893 - 902
(2007/10/02)
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- SYNTHESIS OF 1,3-DIOXIN-4-ONES AND THEIR USE IN SYNTHESIS. XVI. 4-OXO-1,3-DIOXIN-5-CARBOXYLIC ACIDS AND RELATED COMPOUNDS: VERSATILE INTERMEDIATES FOR THE SYNTHESIS OF 6-UNSUBSTITUTED SIX-MEMBERED HETEROCYCLIC COMPOUNDS
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A novel method for the synthesis of so far unknown 1,3-dioxin-4-ones having a carboxyl group at the 5-position is described.Reaction of formyl Meldrum's acid and an alcohol in an aprotic solvent at 50-60 deg C gave the corresponding half esters of formylmalonic acid.Treatment of the latter with appropriate ketones in acetic anhydride containing a catalytic amount of p-toluenesulfonic acid gave the desired dioxinone-5-carboxylates.Successful conversion of these 1,3-dioxin-4-ones either to 1,3-oxazine-2,4-dione or uracil derivatives having an alkoxycarbonyl group at the 5-position demonstrated that these dioxinones can serve as chemical equivalents for alkoxycarbonylformylketenes.The fact that 5-benzyloxycarbonyl-1,3-dioxin-4-one can readily be transformed to the so far unknown 5-aminodioxinone derivative indicates further the importance of the dioxinone having a carboxyl group at the 5-position as a new building block for heterocyclic compounds.Keywords: 4-oxo-1,3-dioxin-5-carboxylic acid; formylmalonic acid half ester; Meldrum's acid; 5-amino-1,3-dioxin-4-one; cycloaddition; 4-oxo-1,3-oxazine-5-carboxylate; 2-dimethylamino-1,3-oxazin-4-one; alkoxycarbonylformylketene
- Sato, Masayuki,Katagiri, Nobuya,Takayama, Kazuhisa,Hirose, Masatoshi,Kaneko, Chikara
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p. 665 - 669
(2007/10/02)
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- A NOVEL SYNTHETIC METHOD OF LACTAMS FROM 1,3-DIOXIN-4-ONES VIA INTRAMOLECULAR KETENE TRAPPING
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A novel route to four- and five-membered lactams from 1,3-dioxin-4-ones having an α-aminoalkyl side-chain at 5- or 6-position through cycloreversion to acylketenes followed by intramolecular ketene trapping by the amino function is described.
- Sato, Masayuki,Ogasawara, Hiromichi,Takayama, Kazuhisa,Kaneko, Chikara
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p. 2611 - 2614
(2007/10/02)
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- General and Versatile Synthetic Method of Formylacetic Esters
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A convenient and large scale preparation of formylacetates 4 by the reaction of alcohols with formylketene (2), readily generated in situ from formyl Meldrum's acid 1, is described.
- Sato, Masayuki,Yoneda, Naoki,Katagiri, Nobuya,Watanabe, Hiroshi,Kaneko, Chikara
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p. 672 - 674
(2007/10/02)
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- A Disilylated Iron Carbonyl Complex as Reagent for the Conversion of Nitriles into Aldehyde-Enamines
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A readily available disilylated iron carbonyl complex converted nitriles into aldehyde-enamines.This chemical transformation is proved to be useful for the reduction of nitriles into aldehydes and for the protection of nitriles.
- Corriu, Robert J.P.,Moreau, Joel J.E.,Pataud-Sat, Magali
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p. 3372 - 3374
(2007/10/02)
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- CATALYZED INSERTION REACTIONS OF SUBSTITUTED Α-DIAZOESTERS. A NEW SYNTHESIS OF CIS-ENOATES
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The decomposition of α-diazoesters is notably catalyst-dependent; with rhodium (II) carboxylates a stereoselective insertion reaction leads to the title structures in high yield.
- Ikota, Nobuo,Takamura, Norio,Young, Stanley D.,Ganem, Bruce
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p. 4163 - 4166
(2007/10/02)
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- 1,4-Dihydropyridine carboxylic acid esters useful as coronary vessel dilators and anti-hypertensives
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Certain 1,4-dihydropyridine carboxylic acid esters or their pharmaceutically acceptable non toxic salts are useful as coronary vessel dilators and antihypertensives.
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