5764-82-9Relevant academic research and scientific papers
The nature of the reformatsky reagent. Crystal structure of (BrZnCH2COO-t-Bu·THF)2
Dekker, Jan,Budzelaar, Peter H. M.,Boersma, Jaap,Van Der Kerk, Gerrit J. M.,Spek, Anthony L.
, p. 1403 - 1407 (1984)
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.
Scalable Continuous Synthesis of Organozinc Reagents and Their Immediate Subsequent Coupling Reactions
Menges-Flanagan, Gabriele,Deitmann, Eva,G?ssl, Lars,Hofmann, Christian,L?b, Patrick
, p. 427 - 433 (2021/01/09)
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.
Reactions of Alkyl 2-(Bromozinc)acylates with N-Chloro- and N-Bromodiethylamines
Zaynashev, A. T.,Zorin, А. V.,Zorin, V. V.
, p. 602 - 605 (2021/06/02)
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
Iridium-catalysed C-H borylation of β-aryl-aminopropionic acids
MacDonald, Simon J. F.,Nortcliffe, Andrew,Robinson, Henry,Simelis, Klemensas,Stillibrand, Joe
supporting information, p. 6696 - 6701 (2020/09/21)
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.
COMPOUND, RESIN, RESIST COMPOSITION AND PRODUCTION METHOD OF RESIST PATTERN
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Paragraph 0223, (2020/10/27)
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
Central zinc metal-controlled regioselective: meso -bromination of zincated β-silylporphyrins - rapid access to meso,β-dual-functionalized porphyrins
Hayashi, Satoshi,Takamatsu, Rina,Takeda, Shiori,Noji, Masahiro,Takanami, Toshikatsu
supporting information, p. 9791 - 9795 (2021/01/05)
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
Fukuyama Cross-Coupling Approach to Isoprekinamycin: Discovery of the Highly Active and Bench-Stable Palladium Precatalyst POxAP
Tang, Shuang-Qi,Bricard, Jacques,Schmitt, Martine,Bihel, Frédéric
supporting information, p. 844 - 848 (2019/01/30)
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.
Inhibition of 3-phosphoglycerate dehydrogenase (PHGDH) by indole amides abrogates de novo serine synthesis in cancer cells
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.
supporting information, p. 2503 - 2510 (2019/07/23)
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.
Method for preparing Sitagliptin intermediate
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Paragraph 0059-0061, (2019/07/16)
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.
Synthesis and RNA-Binding Properties of Extended Nucleobases for Triplex-Forming Peptide Nucleic Acids
Kumpina, Ilze,Brodyagin, Nikita,Mackay, James A.,Kennedy, Scott D.,Katkevics, Martins,Rozners, Eriks
, p. 13276 - 13298 (2019/10/16)
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.
