- Single electron transfer induced elemental steps in the transformation of iodomalonic esters and related CH-acids under solid-liquid PTC conditions. Preparation of electrophilic cyclopropanes
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Single electron transfer induced elemental steps have been shown to occur during the transformation of iodomalonic esters and related CH-acids to cyclopropane derivatives under solid-liquid phase transfer catalytic conditions. The iodo derivatives are formed from iodine and CH-acids "in situ", in the same pot in which the transformations to cyclopropane derivatives take place. A number of electrophilic cyclopropanes with a wide range of substituents have been synthetised by this route.
- Toke, Laszlo,Hell, Zoltan,Szabo, Gabor T.,Toth, Gabor,Bihari, Maria,Rockenbauer, Antal
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Read Online
- Double-[...] compound and its method and use thereof
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The invention provides a type of substituted bicyclic pyrazolone compounds which can be used for inhibiting the activities of receptor tyrosine kinases especially the activities of Axl, Mer, c-Met and Ron kinases. The invention also provides medicine compositions comprising the type of compounds, and applications of the compound and the medicine compositions in drug preparation. The medicines can be used for preventing and treating proliferative diseases or reducing the severity of the diseases.
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Paragraph 0342; 0343; 0413; 0414
(2018/10/11)
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- TYK2 INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.
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Paragraph 00843-00844
(2017/03/21)
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- ANTIBACTERIAL COMPOUNDS
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This invention relates to antibacterial and antimycobacterial drug compounds of formula (I). It also relates to pharmaceutical formulations of antibacterial drug compounds of formula (I). It also relates to uses of the derivatives in treating bacterial infections and to methods of treating bacterial infections. The compounds are particularly useful for treating bacterial infections that have developed resistance to other drug compounds, e.g. resistant strains of S. aureus.
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Page/Page column 110; 111
(2017/04/11)
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- DIHYDROPYRIDINONE MGAT2 INHIBITORS
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The present invention provides compounds of Formula (I): or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are monoacylglycerol acyltransferase type 2 (MGAT2) inhibitors which may be used as medicaments.
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Paragraph 0430
(2016/10/08)
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- Dihydropyridinone MGAT2 inhibitors
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The present invention provides compounds of Formula (I): Formula (I) or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are monoacylglycerol acyltransferase type 2 (MGAT2) inhibitors which may be used as medicaments.
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Paragraph 0465; 0466; 0467
(2016/10/09)
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- argues a row sandbank a method for synthesis of benzoic acid
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The invention discloses a synthetic method of alogliptin benzoate. The synthetic method of the alogliptin benzoate comprises the steps of carrying out amidation reaction on (R)-3-Boc-amino piperidine and ethyl hydrogen malonate which are taken as raw materials to synthesize (R)-3-(3-Boc-amino piperidine-1-yl)-3-oxo ethyl propionate; then carrying out a ring closing reaction on the (R)-3-(3-Boc-amino piperidine-1-yl)-3-oxo ethyl propionate and 1-(2-cyano-benzyl)-3-methylurea; then carrying out deprotection under an acid condition, so that alogliptin is obtained; and finally carrying out salifying on the alogliptin and benzoic acid, so that the alogliptin benzoate is obtained. The synthetic method of the alogliptin benzoate has the advantages that a synthetic route and technology are simplified and optimized, a reagent is easily available, cost is reduced, total yield is relatively high, using requirement can be met by producing the alogliptin benzoate in a large scale, and the synthetic method of the alogliptin benzoate is efficient, environment-friendly and applicable to industrial production.
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Paragraph 0052; 0054-0056
(2018/02/04)
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- Silver-Catalyzed Cyclization of Propargylic Amides to Oxazolines
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A ligand-accelerated effect is observed in the cyclization of propargylic amides catalyzed by bis(pyridyl)silver(I) complexes, with an unexpected reversal of electronic demand to the analogous NH addition reaction. The catalyst was found to be effective for internal alkyne substrates, offering exclusive selectivity for the 5-exo-dig product. Differences in selectivity profile between gold- and silver-catalyzed processes are highlighted and discussed.
- Wong, Valerie H. L.,White, Andrew J. P.,Hor,Hii
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supporting information
p. 3943 - 3948
(2016/01/25)
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- Bidentate ligand 8-aminoquinoline-aided Pd-catalyzed diastereoselective β-arylation of the prochiral secondary sp3 C-H bonds of 2-phenylbutanamides and related aliphatic carboxamides
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Investigations on the Pd-catalyzed 8-aminoquinoline-aided diastereoselective β-arylation of the prochiral 2° sp3 C-H bonds of various aliphatic carboxamides having substituents at the α- or γ-positions are reported. The Pd-catalyzed β-arylation of the 2° sp3 C-H bonds of racemic 2-phenylbutanamides with aryl iodides gave the arylated products (±)-3a-l (anti isomers) with moderate to good diastereoselectivities (dr up to 86:14). Next, the Pd-catalyzed β-arylation of various γ-substituted aliphatic carboxamides with aryl iodides furnished the corresponding C-H arylated products with poor diastereoselectivities. Then, the arylation of the C(β)-H bonds of 2-ethyl-N-(quinolin-8-yl)butanamide possessing two prochiral centers with aryl iodides successfully furnished the bis arylated products meso-8eA-hA and (±)-8eB-hB (diastereomers). The arylation of (S)-2-phenylbutanamide also gave the corresponding enantiomerically enriched compounds 10a-c (anti isomers). The stereochemistry of the products (±)-3a-l (major isomers), meso-8eA-hA (major isomers), (±)-8eB-hB (minor isomers) and enantiomerically enriched compounds 10a-c (major isomers) were assigned based on the X-ray structures of the major isomers 3b,c,e,l, 8eA, 10c and minor isomers 8eB and 8fB. The limitations and outcome of the stereocontrol in the Pd-catalyzed C-H arylation reactions involving aliphatic carboxamides are illustrated.
- Gopalakrishnan, Bojan,Babu, Srinivasarao Arulananda,Padmavathi, Rayavarapu
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p. 8333 - 8349
(2015/10/05)
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- BICYLCIC PYRAZOLONE COMPOUNDS AND METHODS OF USE
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The present invention provides substituted bicyclic pyrazolone compounds, which are used to inhibit or modulate the activity of receptor tyrosine kinases, especially Axl, Mer, c-Met and Ron. The invention also provides pharmaceutical compositions comprising the compound disclosed herein, and a method of preventing, treating or lessening the severity of a proliferative disorder in a patient with the compounds or the pharmaceutical compositions disclosed herein.
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Paragraph 0242; 0256
(2015/11/16)
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- HIV INTEGRASE INHIBITORS
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The present invention features compounds that are HIV integrase inhibitors and therefore are useful in the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC.
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- Base-switched annuloselectivity in the reactions of ethyl malonyl chloride and imines
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The base-switched annuloselectivity, namely [2 + 2] and [2 + 2 + 2] selectivity, in the reactions of ethyl malonyl chloride and imines is successfully realized. In the presence of the weak nucleophilic base 2-chloropyridine, the reactions deliver ethyl trans-β-lactam-3-carboxylates as the exclusive [2 + 2] products in up to 93% yields, while with the strong nucleophilic N-methylimidazole as the base, the reactions give rise to 2,3-dihydro-1,3-oxazin-4-one derivatives as the sole products in up to 99% yields via the formal [2 + 2 + 2] cycloaddition involving one molecule of the imine and two molecules of the ketene generated from malonyl chloride. Notably, ethyl trans-β-lactam-3-carboxylates are synthesized for the first time directly from the reactions of ethyl malonyl chloride and imines. Mechanistic discussions reveal that the annuloselectivity is controlled by the nucleophilicity of organic bases. This journal is
- Yang, Zhanhui,Li, Siqi,Zhang, Zhong,Xu, Jiaxi
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p. 9822 - 9830
(2015/01/08)
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- Synthesis of diverse N, O-bridged calix[1]arene[4]pyridine-C60 dyads and triads and formation of intramolecular self-inclusion complexes
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Starting from both the bridging nitrogen atom-functionalized and the upper rim-functionalized N,O-bridged calix[1]arene[4]pyridine reactants, different types of heteracalixaromatics-C60 dyads and triads of varied spacers were expediently synthesized using mainly the click reaction as the key step. By means of various spectroscopic methods, the heteracalixaromatics-C60 dyads and triads obtained have been shown to form intramolecular self-inclusion complexes rather than oligomers or polymers in solution because of a flexible spacer in between the heteracalixaromatic ring and C60 moiety. The current study, coupled with previous investigations, would provide the guideline for the construction of supramolecular fullerene motifs based on molecular design of the dyads and triads.
- Wu, Jin-Cheng,Wang, De-Xian,Huang, Zhi-Tang,Wang, Mei-Xiang
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supporting information; experimental part
p. 8604 - 8614
(2011/03/22)
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- trans-directing ability of amide groups in cyclopropanation: Application to the asymmetric cyclopropanation of alkenes with diazo reagents bearing two carboxy groups
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(Chemical Equation Presented) Highly stereoselective: A highly enantioselective (up to 97 % ee) and diastereoselective (>30:1 d.r.) Rh II-catalyzed cyclopropanation of alkenes using a diazo reagent bearing two carboxy groups is described. This new methodology exploits the powerful trans-directing ability of amides to improve enantiocontrol. Mono- and disubstituted olefins are cyclopropanated in good yields. nttl=N-1,8-naphthoyl- tert-leucine.
- Marcoux, David,Charette, Andre B.
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supporting information; experimental part
p. 10155 - 10158
(2009/05/30)
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- New competitive inhibitors of cytosolic (NADH-dependent) rabbit muscle glycerophosphate dehydrogenase
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We report the synthesis and biochemical evaluation of new competitive inhibitors of the cytosolic (NADH-dependent) glycerophosphate dehydrogenase. The best tested compound, phosphono-propionohydroxamic acid, with a Ki of 6 μM, might be of interest as an anti-obesity drug.
- Fonvielle, Matthieu,Therisod, Helene,Hemery, Marion,Therisod, Michel
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p. 410 - 413
(2007/10/03)
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- Methods for the synthesis of highly substituted 2,4-dioxopiperidine libraries
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The invention relates to methods of synthesizing libraries of diverse and complex highly substituted 2,4-dioxopiperidine compounds of the general formula: wherein R1, R2 and R3 are as herein described, novel intermediates useful for synthesizing such 2,4-dioxopiperidine compounds and methods for identifying and isolating the compounds.
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- Synthesis of fused systems in the isoquinoline series: Oxazolo- and pyrrolo[3,2-c]isoquinolines
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In order to synthesize the pyrrolo[3,2-c]isoquinoline structure, three different routes starting from readily available isoquinolines were tried. The ring closure reaction of a malonic derivative of 4-amino-3- bromoisoquinoline led to an oxazolo[3,2-c]isoquinoline instead of the target molecule. This latter was obtained via Sonagashira coupling reaction followed by ring closure under basic conditions. A study of the lithiation of the N- sulfonated pyrrolo[3,2-c]isoquinoline was undertaken. After optimization of the lithiation conditions, various 2-substituted pyrrolo[3,2-c]isoquinolines were obtained and their oxidation reactions studied.
- Briere, Jean-Francois,Dupas, Georges,Queguiner, Guy,Bourguignon, Jean
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p. 1371 - 1383
(2007/10/03)
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- THE SYNTHESIS OFβ-LACTONES AND β-LACTAMS FROM MALONATES AND MALONAMIDES
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The rhodium diacetate induced insertion reactions of some simple esters and amides of diazomalonic acid result in the formation of β-lactones and β-lactams.
- Box, Vernon G. S.,Marinovic, Nash,Yiannikouros, George P.
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p. 245 - 251
(2007/10/02)
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- Synthesis of 4-Alkyl-2(5H)-furanones
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An alternative method for the synthesis of 4-alkyl-2(5H)-furanones is described.Intramolecular carbene addition reaction of α-diazo compounds (4) in the presence of rhodium acetate or copper acetylacetonate furnished the bicyclic compounds (5), which were subjected to cyclopropane ring-opening reaction to give the 4-alkyl-4,5-dihydrofuran-2(3H)-ones (6) regioselectively.These compounds (6) were further converted into 4-alkyl-2(5H)-furanones (14) in several steps.Keywords - carbene; intramolecular addition; butenolide; cyclopropanation; ring-opening reaction
- Kametani, Tetsuji,Katoh, Tadashi,Tsubuki, Masayoshi,Honda, Toshio
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- Intramolecular N-H, O-H, and S-H Insertion Reactions. Synthesis of Heterocycles from α-Diazo β-Keto Esters
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Several aspects of the Rh2(OAc)4-catalyzed intramolecular N-H, O-H, and S-H insertion reactions have been studied.Examination of the effect of ring size revealed that four-, five- and six-membered nitrogen heterocycles can be efficiently prepared from the corresponding α-diazo β-keto ester precursors (9a-c), whereas competing C-H insertion prevented formation of the seven-membered heterocycle.Variations in solvent, temperature, and catalyst concentration were found to play an important role in determining the product distribution in the cyclization of the 6-carbamoyl 2-diazo 3-keto ester 9c.The intramolecular X-H insertion reaction has also been successful in the synthesis of oxygen (39) and sulfur (49) heterocycles as well as a heterocycle containing two (N, O) heteroatoms (34).
- Moyer, Mikel P.,Feldman, Paul L.,Rapoport, Henry
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p. 5223 - 5230
(2007/10/02)
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