- The nature of the reformatsky reagent. Crystal structure of (BrZnCH2COO-t-Bu·THF)2
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The nature of the Reformatsky reagents derived from the ethyl and tert-butyl esters of bromoacetic acid has been studied by association measurements and NMR spectroscopy in various solvents. It appears that the reagents are dimeric in all but the most polar solvents. A dimeric structure containing both Zn-O and Zn-C single bonds is present in the crystalline state of (BrZnCH2COO-t-Bu·THF)2, the final X-ray analysis of which is reported. Crystals are monoclinic of space group P21/n with two dimers in a cell of dimensions a = 10.322 (3) A?, b = 12.358 (3) A?, c = 11.655 (2) A?, and β = 112.65 (2)°. The structure was refined to R = 0.055 on 881 observed reflections with I > 2.5σ(I). It is concluded that the dimeric structure found in the crystal persists in solution. In the very polar solvent Me2SO, the reagents are monomeric C-metalated species. The consequences of these findings for the mechanism of the Reformatsky reaction in the commonly used solvents are discussed.
- Dekker, Jan,Budzelaar, Peter H. M.,Boersma, Jaap,Van Der Kerk, Gerrit J. M.,Spek, Anthony L.
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Read Online
- Scalable Continuous Synthesis of Organozinc Reagents and Their Immediate Subsequent Coupling Reactions
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The continuous synthesis of organozinc reagents and their immediately following subsequent also continuous consumption in catalyzed and noncatalyzed coupling reactions were investigated. In the first step, a bed of Zn turnings at variable liquid throughputs and concentrations of organic halide solutions was used, and the formed Zn organometallics were analyzed for quality control. They were then directly pumped into a second step, namely, Reformatsky, Saytzeff, and Negishi coupling reactions. In the organozinc halides' formation, a novel process window was employed by using a large molar excess of Zn turnings and investigating mechanical as well as chemical Zn activation. Subsequent couplings of the freshly prepared Zn organometallics were done using examples of a Reformatsky, Saytzeff, and Negishi coupling reaction. For the Zn organometallics' formation, a laboratory-scale reactor setup previously built for Grignard reagent formation was evaluated including a Zn replenishing unit; the same reactor was also used in the metal-catalyzed subsequent step (Negishi coupling). The main objective of this work was to establish the scalable continuous formation of Zn organometallic reagents enabling fast and safe process optimization, analyze the reagents for their purity, and then immediately consume them in various follow-up steps, always only leaving a very small amount of reactive and sensitive organometallic reagent in the setup. It was found that full conversion of the employed halides could be achieved within a single passage through the reactor with organozinc yields of 82-92%, as well as being able to successfully perform subsequent non- and metal-catalyzed coupling steps with yields of up to 92%. A pilot-scale setup allowing a liquid throughput of up to 3-5 L/h has also been built and is ready to be tested with the synthesis as established here.
- Menges-Flanagan, Gabriele,Deitmann, Eva,G?ssl, Lars,Hofmann, Christian,L?b, Patrick
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p. 427 - 433
(2021/01/09)
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- Reactions of Alkyl 2-(Bromozinc)acylates with N-Chloro- and N-Bromodiethylamines
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Abstract: The reaction of alkyl 2-(bromozinc)acylates, obtained from ethyl bromoacetate (or butyl 2-bromobutanoate, or butyl 2-bromo-2-methylpropanoate) under the action of zinc, with N-chloro- or N-bromodiethylamine in tetrahydrofuran at 20–25°C under ar
- Zaynashev, A. T.,Zorin, А. V.,Zorin, V. V.
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p. 602 - 605
(2021/06/02)
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- Iridium-catalysed C-H borylation of β-aryl-aminopropionic acids
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Iridium-catalysed catalytic, regioselective C-H borylation of β-aryl-aminopropionic acid derivatives gives access to 3,5-functionalised protected β-aryl-aminopropionic acid boronates. The synthetic versatility of these new boronates is demonstrated through sequential one-pot functionalisation reactions to give diverse building blocks for medicinal chemistry. The C-H borylation is also effective for dipeptide substrates. We have exemplified this methodology in the synthesis of a pan αv integrin antagonist.
- MacDonald, Simon J. F.,Nortcliffe, Andrew,Robinson, Henry,Simelis, Klemensas,Stillibrand, Joe
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supporting information
p. 6696 - 6701
(2020/09/21)
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- COMPOUND, RESIN, RESIST COMPOSITION AND PRODUCTION METHOD OF RESIST PATTERN
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PROBLEM TO BE SOLVED: To provide a compound from which a resist pattern with good line edge roughness (LER) can be produced. SOLUTION: The compound is represented by formula (I). In the formula, R1 represents an alkyl group having 1 to 6 carbon atoms, H, or a halogen atom; X1 represents a connecting group such as -COO-C6H5-COO-; A1 represents a single bond or the like; A3 represents an alkanediyl group having 1 to 6 carbon atoms; W represents a divalent alicyclic hydrocarbon group having 3 to 18 carbon atoms; and R2 represents a substituted/unsubstituted hydrocarbon group having 1 to 28 carbon atoms. SELECTED DRAWING: None COPYRIGHT: (C)2021,JPO&INPIT
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Paragraph 0223
(2020/10/27)
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- Central zinc metal-controlled regioselective: meso -bromination of zincated β-silylporphyrins - rapid access to meso,β-dual-functionalized porphyrins
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A convenient method for the preparation of meso,β-dual-functionalized porphyrin was developed. The bromination of zincated β-silylporphyrin with NBS selectively yielded meso-bromo-β-silylporphyrin, whereas, the bromination of free-base β-silylporphyrin selectively yielded β-bromoporphyrin via an ipso-substitution of the silyl group. These meso,β-dual-functionalized porphyrins could be used as multipurpose synthons for fabricating various porphyrin derivatives. This journal is
- Hayashi, Satoshi,Takamatsu, Rina,Takeda, Shiori,Noji, Masahiro,Takanami, Toshikatsu
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supporting information
p. 9791 - 9795
(2021/01/05)
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- Fukuyama Cross-Coupling Approach to Isoprekinamycin: Discovery of the Highly Active and Bench-Stable Palladium Precatalyst POxAP
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An efficient and user-friendly palladium(II) precatalyst, POxAP (post-oxidative-addition precatalyst), was identified for use in Fukuyama cross-coupling reactions. Suitable for storage under air, the POxAP precatalyst allowed reaction between thioesters and organozinc reagents with turnover numbers of ~90000. A series of 23 ketones were obtained with yields ranging from 53 to 99%. As proof of efficacy, an alternative approach was developed for the synthesis of a key precursor of the natural product isoprekinamycin.
- Tang, Shuang-Qi,Bricard, Jacques,Schmitt, Martine,Bihel, Frédéric
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supporting information
p. 844 - 848
(2019/01/30)
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- Inhibition of 3-phosphoglycerate dehydrogenase (PHGDH) by indole amides abrogates de novo serine synthesis in cancer cells
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Cancer cells reprogram their metabolism to support growth and to mitigate cellular stressors. The serine synthesis pathway has been identified as a metabolic pathway frequently altered in cancers and there has been considerable interest in developing pharmacological agents to target this pathway. Here, we report a series of indole amides that inhibit human 3-phosphoglycerate dehydrogenase (PHGDH), the enzyme that catalyzes the first committed step of the serine synthesis pathway. Using X-ray crystallography, we show that the indole amides bind the NAD+ pocket of PHGDH. Through structure-based optimization we were able to develop compounds with low nanomolar affinities for PHGDH in an enzymatic IC50 assay. In cellular assays, the most potent compounds inhibited de novo serine synthesis with low micromolar to sub-micromolar activities and these compounds successfully abrogated the proliferation of cancer cells in serine free media. The indole amide series reported here represent an important improvement over previously published PHGDH inhibitors as they are markedly more potent and their mechanism of action is better defined.
- Mullarky, Edouard,Xu, Jiayi,Robin, Anita D.,Huggins, David J.,Jennings, Andy,Noguchi, Naoyoshi,Olland, Andrea,Lakshminarasimhan, Damodharan,Miller, Michael,Tomita, Daisuke,Michino, Mayako,Su, Taojunfeng,Zhang, Guoan,Stamford, Andrew W.,Meinke, Peter T.,Kargman, Stacia,Cantley, Lewis C.
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supporting information
p. 2503 - 2510
(2019/07/23)
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- Method for preparing Sitagliptin intermediate
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The invention belongs to the field of organic synthesis and particularly relates to a method for preparing a Sitagliptin intermediate. The intermediate has a structure represented by a formula A shownin the description, wherein R1 and R2 are the same, or are differently hydrogen or C1-C5 alkyl, more preferably, R1 is tert-butyl, and R2 is hydrogen.
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-
Paragraph 0059-0061
(2019/07/16)
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- Synthesis and RNA-Binding Properties of Extended Nucleobases for Triplex-Forming Peptide Nucleic Acids
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Triple-helix formation, using Hoogsteen hydrogen bonding of triplex-forming oligonucleotides, represents an attractive method for sequence-specific recognition of double-stranded nucleic acids. However, practical applications using triple-helix-forming oligonucleotides and their analogues are limited to long homopurine sequences. The key problem for recognition of pyrimidines is that they present only one hydrogen-bond acceptor or donor group in the major groove. Herein, we report our first attempt to overcome this problem by using peptide nucleic acids (PNAs) modified with extended nucleobases that form three hydrogen bonds along the entire Hoogsteen edge of the Watson-Crick base pair. New nucleobase triples (five) were designed, and their hydrogen bonding feasibility was confirmed by ab initio calculations. PNA monomers carrying the modified nucleobases were synthesized and incorporated in short model PNA sequences. Isothermal titration calorimetry showed that these nucleobases had a modest binding affinity for their double-stranded RNA (dsRNA) targets. Finally, molecular modeling of the modified triples in PNA-dsRNA helix suggested that the modest binding affinity was caused by subtle structural deviations from ideal hydrogen-bonding arrangements or disrupted π-stacking of the extended nucleobase scaffolds.
- Kumpina, Ilze,Brodyagin, Nikita,Mackay, James A.,Kennedy, Scott D.,Katkevics, Martins,Rozners, Eriks
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p. 13276 - 13298
(2019/10/16)
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- Ultrasound assisted nitratobis(triphenyl phosphine) copper(I) catalyzed conjugate addition of alkyl or aryl bromides to α,β-unsaturated cyanoester
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The α,β-unsaturated cyanoester was obtained from p-methoxy benzaldehyde and ethyl cyano acetate by reported method. The conjugated addition products were synthesized from alkyl or aryl bromides and α,β-unsaturated cyanoester in the presence of 10 mol % Cu(I) catalyst in high yields within 17-21 min under ultrasound irradiation.
- Pise, Ashok S.,Burungale, Arvind S.,Devkate, Santosh S.,Gawade, Ramesh B.,Jadhav, Sunil D.
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p. 348 - 352
(2019/01/19)
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- RORGAMMA MODULATORS AND USES THEREOF
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The present invention provides novel compounds that are modulators of RORgamma. These compounds, and pharmaceutical compositions comprising the same, are suitable means for treating any disease wherein the modulation of RORgamma has therapeutic effects, for instance in autoimmune diseases, autoimmune-related diseases, inflammatory diseases, metabolic diseases, fibrotic diseases, or cholestatic diseases.
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Page/Page column 35; 45-46
(2018/09/08)
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- RORGAMMA MODULATORS AND USES THEREOF
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The present invention provides novel compounds of formula (la) that are modulators of RORgamma. These compounds, and pharmaceutical compositions comprising the same, are suitable means for treating any disease wherein the modulation of RORgamma has therapeutic effects, for instance in autoimmune diseases, autoimmune-related diseases, inflammatory diseases, metabolic diseases, fibrotic diseases, or cholestatic diseases.
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Page/Page column 41; 59
(2018/08/20)
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- BENZODIAZEPINES AS BROMODOMAIN INHIBITORS
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The present invention provides novel benzodiazepine derivatives of Formula I or pharmaceutically acceptable derivatives, polymorphs, salts or prodrugs thereof. Said compounds have potential as bromodomain (BRD) inhibitors.
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Page/Page column 100
(2017/02/28)
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- 3-PHOSPHOGLYCERATE DEHYDROGENASE INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 00657; 00658
(2017/10/06)
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- 3-PHOSPHOGLYCERATE DEHYDROGENASE INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 00541; 00542
(2017/09/27)
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- Chemically Diverse Group i p21-Activated Kinase (PAK) Inhibitors Impart Acute Cardiovascular Toxicity with a Narrow Therapeutic Window
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p21-activated kinase 1 (PAK1) has an important role in transducing signals in several oncogenic pathways. The concept of inhibiting this kinase has garnered significant interest over the past decade, particularly for targeting cancers associated with PAK1 amplification. Animal studies with the selective group I PAK (pan-PAK1, 2, 3) inhibitor G-5555 from the pyrido[2,3-d]pyrimidin-7-one class uncovered acute toxicity with a narrow therapeutic window. To attempt mitigating the toxicity, we introduced significant structural changes, culminating in the discovery of the potent pyridone side chain analogue G-9791. Mouse tolerability studies with this compound, other members of this series, and compounds from two structurally distinct classes revealed persistent toxicity and a correlation of minimum toxic concentrations and PAK1/2 mediated cellular potencies. Broad screening of selected PAK inhibitors revealed PAK1, 2, and 3 as the only overlapping targets. Our data suggest acute cardiovascular toxicity resulting from the inhibition of PAK2, which may be enhanced by PAK1 inhibition, and cautions against continued pursuit of pan-group I PAK inhibitors in drug discovery.
- Rudolph, Joachim,Murray, Lesley J.,Ndubaku, Chudi O.,O'Brien, Thomas,Blackwood, Elizabeth,Wang, Weiru,Aliagas, Ignacio,Gazzard, Lewis,Crawford, James J.,Drobnick, Joy,Lee, Wendy,Zhao, Xianrui,Hoeflich, Klaus P.,Favor, David A.,Dong, Ping,Zhang, Haiming,Heise, Christopher E.,Oh, Angela,Ong, Christy C.,La, Hank,Chakravarty, Paroma,Chan, Connie,Jakubiak, Diana,Epler, Jennifer,Ramaswamy, Sreemathy,Vega, Roxanne,Cain, Gary,Diaz, Dolores,Zhong, Yu
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p. 5520 - 5541
(2016/07/06)
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- I2-Mediated 2: H -indazole synthesis via halogen-bond-assisted benzyl C-H functionalization
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I2-Mediated benzyl C-H functionalization has been developed for the synthesis of 2H-indazoles, which features high efficiency, simple conditions and no need for metals. Mechanistic experiments and DFT calculations have revealed halogen bond assistance and a radical chain process for this reaction. The azo group and the bound iodine cooperate in the hydrogen abstraction step, which circumvents the thermodynamic disfavor of direct hydrogen abstraction by a simple iodine radical.
- Yi, Xiangli,Jiao, Lei,Xi, Chanjuan
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supporting information
p. 9912 - 9918
(2016/10/31)
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- Design, Synthesis, and Biological Evaluation of First-in-Class Dual Acting Histone Deacetylases (HDACs) and Phosphodiesterase 5 (PDE5) Inhibitors for the Treatment of Alzheimer's Disease
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Simultaneous inhibition of phosphodiesterase 5 (PDE5) and histone deacetylases (HDAC) has recently been validated as a potentially novel therapeutic approach for Alzheimer's disease (AD). To further extend this concept, we designed and synthesized the first chemical series of dual acting PDE5 and HDAC inhibitors, and we validated this systems therapeutics approach. Following the implementation of structure- and knowledge-based approaches, initial hits were designed and were shown to validate our hypothesis of dual in vitro inhibition. Then, an optimization strategy was pursued to obtain a proper tool compound for in vivo testing in AD models. Initial hits were translated into molecules with adequate cellular functional responses (histone acetylation and cAMP/cGMP response element-binding (CREB) phosphorylation in the nanomolar range), an acceptable therapeutic window (>1 log unit), and the ability to cross the blood-brain barrier, leading to the identification of 7 as a candidate for in vivo proof-of-concept testing (Cuadrado-Tejedor, M.; Garcia-Barroso, C.; Sánchez-Arias, J. A.; Rabal, O.; Mederos, S.; Ugarte, A.; Franco, R.; Segura, V.; Perea, G.; Oyarzabal, J.; Garcia-Osta, A. Neuropsychopharmacology 2016, in press, doi: 10.1038/npp.2016.163).
- Rabal, Obdulia,Sánchez-Arias, Juan A.,Cuadrado-Tejedor, Mar,De Miguel, Irene,Pérez-González, Marta,García-Barroso, Carolina,Ugarte, Ana,Estella-Hermoso De Mendoza, Ander,Sáez, Elena,Espelosin, Maria,Ursua, Susana,Haizhong, Tan,Wei, Wu,Musheng, Xu,Garcia-Osta, Ana,Oyarzabal, Julen
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supporting information
p. 8967 - 9004
(2016/10/22)
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- NOVEL COMPOUNDS FOR USE IN COGNITION IMPROVEMENT
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Novel compounds for use in cognition improvement It relates to certain compounds having a polycyclic structure and a -(C=O)NRaRb moiety, wherein the polycyclic structure comprises at least three ring systems, wherein one ring system is a polycyclic ring system comprising from 2 to 4 rings; at least one ring is an aromatic ring; and wherein the structure comprises at least 3 nitrogen atoms and 1 oxygen atom. It also relates to pharmaceutical compositions containing them, and to their use in medicine, in particular in the treatment and/or prevention of neurological disorders coursing with a cognition deficit or impairment, or neurodegenerative diseases.
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Page/Page column 47; 48
(2016/04/19)
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- Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-pKa Polar Moiety
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Signaling pathways intersecting with the p21-activated kinases (PAKs) play important roles in tumorigenesis and cancer progression. By recognizing that the limitations of FRAX1036 (1) were chiefly associated with the highly basic amine it contained, we devised a mitigation strategy to address several issues such as hERG activity. The 5-amino-1,3-dioxanyl moiety was identified as an effective means of reducing pKa and logP simultaneously. When positioned properly within the scaffold, this group conferred several benefits including potency, pharmacokinetics, and selectivity. Mouse xenograft PK/PD studies were carried out using an advanced compound, G-5555 (12), derived from this approach. These studies concluded that dose-dependent pathway modulation was achievable and paves the way for further in vivo investigations of PAK1 function in cancer and other diseases.
- Ndubaku, Chudi O.,Crawford, James J.,Drobnick, Joy,Aliagas, Ignacio,Campbell, David,Dong, Ping,Dornan, Laura M.,Duron, Sergio,Epler, Jennifer,Gazzard, Lewis,Heise, Christopher E.,Hoeflich, Klaus P.,Jakubiak, Diana,La, Hank,Lee, Wendy,Lin, Baiwei,Lyssikatos, Joseph P.,Maksimoska, Jasna,Marmorstein, Ronen,Murray, Lesley J.,O'Brien, Thomas,Oh, Angela,Ramaswamy, Sreemathy,Wang, Weiru,Zhao, Xianrui,Zhong, Yu,Blackwood, Elizabeth,Rudolph, Joachim
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supporting information
p. 1241 - 1246
(2015/12/23)
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- SERINE/THREONINE KINASE INHIBITORS
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Compounds having the formula I wherein R1, R2, R3, R4, R5, Ra, Rb, Rc, Rd, Re, n, r, s and t are as defined herein and which compounds are inhibitors of PAK1. Also disclosed are compositions and methods for treating cancer and hyperproliferative disorders.
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Paragraph 0349
(2015/02/19)
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- Synthesis of Azepines via a [6 + 1] Annulation of Ynenitriles with Reformatsky Reagents
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A protocol for the direct synthesis of azepines using a hafnium(III)-catalyzed [6 + 1] annulation of N-tethered ynenitriles with Reformatsky reagents is reported. A broad range of 3-amino-2,7-dihydro-1H-azepine-4-carboxylates 4aa-4he were obtained in high yields and with excellent functional group tolerance. The copper-mediated reactions of isolable Blaise intermediates (enamino esters 3), uniquely underwent 5-endo cyclization to afford the β-2,5-dihydropyrrolyl α,β-unsaturated esters 5aa-5fc, which exhibit anticancer activity.
- Yoshimatsu, Mitsuhiro,Tanaka, Miki,Fujimura, Yu,Ito, Yukiteru,Goto, Yusuke,Kobayashi, Yuka,Wasada, Hiroaki,Hatae, Noriyuki,Tanabe, Genzoh,Muraoka, Osamu
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p. 9480 - 9494
(2015/10/12)
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- NOVEL COMPOUNDS AS DUAL INHIBITORS OF PHOSPHODIESTERASES AND HISTONE DEACETYLASES
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It relates to certain compounds having a polycyclic structure and a hydroxamic acid moiety, wherein the polycyclic structure comprises at least three ring systems, wherein one ring system is a polycyclic ring system comprising from 2 to 4 rings; at least one ring is an aromatic ring; and wherein the structure comprises at least 3 nitrogen atoms and 1 oxygen atom. It also relates to a process for their preparation, as well as to pharmaceutical compositions containing them, and to their use in medicine, in particular in the treatment and/or prevention of neurological disorders coursing with a cognition deficit or impairment, or neurodegenerative diseases. wherein B1 is a radical selected from the group consisting of formula (A"), formula (B"), formula (C"), and formula (D"):
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Page/Page column 77; 78
(2014/09/16)
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- 6-(5-HYDROXY-1H-PYRAZOL-1-YL)NICOTINAMIDE DERIVATIVES AND THEIR USE AS PHD INHIBITORS
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The present invention provides compounds of formula (I) which are useful as inhibitors of PHD, pharmaceutical compositions thereof, methods for treatment of conditions associated with HIF, processes for making the compounds and intermediates thereof.
- -
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Paragraph 0136; 0137
(2014/10/15)
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- Reaction of organozinc halides with aryl isocyanates
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Reformatsky reagent, benzylzinc bromide or alkylzinc iodides react with aryl isocyanates directly to give corresponding N-substituted carbamates under mild reaction conditions. However, the reaction of allylzinc bromide or propargylzinc bromide with aryl isocyanates produces the corresponding N-substituted amides. The reactions provide alternative methods for the synthesis of N-substituted carbamates or amides.
- Yang, Haoran,Huang, Danfeng,Wang, Ke-Hu,Xu, Changming,Niu, Teng,Hu, Yulai
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supporting information
p. 2588 - 2593
(2013/03/28)
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- Double reformatsky reaction: Divergent synthesis of δ-hydroxy-β- ketoesters
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The double Reformatsky reaction, tandem addition of two molecules of zinc alkanoate to a carbonyl compound, and its synthetic application to a series of δ-hydroxy-β-ketoesters has been developed. The key to accelerate the double Reformatsky reaction is considered to be a complex-induced proximity effect of the in situ generated zinc alkoxide coordinated with the pyridyl group of the substrate or bidentate amines. A noteworthy feature of the reaction system is its high tolerance of functional groups due to the moderate nucleophilicity of organozinc reagents and the mild reaction conditions. Moreover, spectroscopic and crystallographic analyses of the zinc complex of the double Reformatsky product support the proposed mechanism of reaction site discrimination for ketones, aldehydes, nitriles, carboxylic acid anhydrides, and esters.
- Mineno, Masahiro,Sawai, Yasuhiro,Kanno, Kazuaki,Sawada, Naotaka,Mizufune, Hideya
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p. 5843 - 5850
(2013/07/26)
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- A rapid and diverse construction of 6-substituted-5,6-dihydro-4-hydroxy-2- pyrones through double Reformatsky reaction
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A rapid and diverse synthesis of biologically important 6-substituted-5,6-dihydro-4-hydroxy-2-pyrones through a double Reformatsky reaction of aldehydes to δ-hydroxy-β-ketoesters followed by lactonization is described. Due to the high functional group tolerance and reaction site discrimination between aldehyde, nitrile, and ester groups in the substrate, the protocol can provide the dihydropyrones with bromo, nitro, carboxylic acid, and β-ketoester groups, which are suitable for the further derivatizations. Furthermore, the protocol has been successfully applied to the rapid total synthesis of naturally occurring Yangonin.
- Mineno, Masahiro,Sawai, Yasuhiro,Kanno, Kazuaki,Sawada, Naotaka,Mizufune, Hideya
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p. 10921 - 10926
(2014/01/06)
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- A novel ketone olefination via organozinc reagents in the presence of diphenyl phosphite
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Carbonyl compounds react with organozinc reagents in the presence of diphenyl phosphite to give the corresponding olefins. A variety of 1,3-dienes and unsaturated esters were obtained in moderate to excellent yields under mild conditions. The Royal Society of Chemistry 2012.
- Cui, Hua,Li, Ying,Zhang, Songlin
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supporting information
p. 2862 - 2869
(2012/11/07)
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- PRODUCTION METHOD OF IMIDAZOLE DERIVATIVES
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The present invention provides an advantageous production method of an imidazole derivative, which is suitable for industrial production. Compound (VI) is produced by reacting compound (I) with a Grignard reagent or a magnesium reagent, and a lithium reagent, and then reacting the resulting compound with compound (V).
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Page/Page column 40
(2013/02/28)
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- PROCESS FOR PRODUCING FUSED IMIDAZOLE COMPOUND, REFORMATSKY REAGENT IN STABLE FORM, AND PROCESS FOR PRODUCING THE SAME
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The present invention provides an industrially advantageous process for producing a steroid C17,20 lyase inhibitor represented by the general formula (I): and a Reformatsky reagent in a stable form suitable for the process.In the present invention, a compound represented by the general formula (I) is produced by reducing a specific β-hydroxy ester compound derivative or a salt thereof obtained from a specific carbonyl compound in a Reformatsky reaction in the presence of a metal hydride complex and a metal halide, and then subjecting it to a ring-closing reaction. In the above Reformatsky reaction, it is useful to use a stable solution of a compound represented by the general formula BrZnCH2COOC2H5 or a crystal of the compound which is represented by the formula (BrZnCH2COOC2H5·THF)2.
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- KINASE INHIBITORS
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The present invention provides kinase inhibitors of Formula (I)
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Page/Page column 18
(2010/02/07)
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- SYNTHESE ORGANOMETALLIQUE D'α-AMINOESTERS N,N-DISUBSTITUES
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Reaction of organozinc compounds with a particular gem-aminoether ester, i.e. methyl-N,N-diethylamino methoxyacetate, leads to α-aminoesters.This method allows the synthesis of compounds having potential biological activity, viz. β-unsaturated α-aminoesters.
- Bourhis, Mireille,Bosc, Jean-Jacques,Golse, Rene
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p. 193 - 202
(2007/10/02)
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