- A N - benzyl ethanolamine preparation method
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A N - benzyl ethanolamine preparation method, including the use of ethanolamine and benzyl chloride as the raw material, to solid phase alkali as the reaction of the acid and alkaline catalyst, in the 40 - 120 °C under stirring to carry out the condensation reaction, the reaction after the stop of the take methylethanone, the filtrate to carry out rectification under vacuum, collecting the fraction, product N - benzyl ethanolamine. This invention adopts the solid phase alkali to [...] and catalytic, through the solid-liquid two-phase are a temperature and reaction to improve the main the selectivity of the reaction, in order to improve the synthetic yield; compared with original craft, saves the sodium hydroxide solution used for washing with ethyl acetate extraction of complex process a plurality of times; at the same time as solid phase alkali acid and alkaline catalyst with hydrogen chloride the reaction generates sodium chloride, convenient recycling, realizes the zero discharge of waste water; improves the ethanolamine utilization rate of the raw material; the invention is not only simple and convenient operation, production process economic and environmental protection, few by-products, and the synthetic yield has been raised by 25 - 30%, preparation and reducing the cost to 30 - 35%.
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Paragraph 0023-0028
(2019/06/05)
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- Photoredox-Catalyzed Site-Selective α-C(sp3)?H Alkylation of Primary Amine Derivatives
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The synthetic utility of tertiary amines to oxidatively generate α-amino radicals is well established, however, primary amines remain challenging because of competitive side reactions. This report describes the site-selective α-functionalization of primary amine derivatives through the generation of α-amino radical intermediates. Employing visible-light photoredox catalysis, primary sulfonamides are coupled with electron-deficient alkenes to efficiently and mildly construct C?C bonds. Interestingly, a divergence between intermolecular hydrogen-atom transfer (HAT) catalysis and intramolecular [1,5] HAT was observed through precise manipulation of the protecting group. This dichotomy was leveraged to achieve excellent α/δ site-selectivity.
- Ashley, Melissa A.,Yamauchi, Chiaki,Chu, John C. K.,Otsuka, Shinya,Yorimitsu, Hideki,Rovis, Tomislav
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supporting information
p. 4002 - 4006
(2019/02/24)
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- Design, synthesis and antimycobacterial activity of novel imidazo[1,2-a]pyridine-3-carboxamide derivatives
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We report herein the design and synthesis of “novel imidazo [1,2-a]pyridine-3-carboxamides (IPAs)” bearing a variety of different linkers, based on the structure of IMB-1402 discovered in our lab. Results reveal that 2,6-dimethyl-N-[2-(phenylamino)ethyl] IPAs with an electron-donating group on the benzene ring as a potent scaffold. Compounds 26g and 26h have considerable activity (MIC: 0.041–2.64 μM) against drug-sensitive/resistant MTB strains, and they have acceptable safety indices against MTB H37Rv with the SI values of 4395 and 1405, respectively. Moreover, N-[2-(piperazin-1-yl)ethyl] moiety was also identified as a potentially alternative linker (compound 31), opening a new direction for further SAR studies.
- Lv, Kai,Li, Linhu,Wang, Bo,Liu, Mingliang,Wang, Bin,Shen, Weiyi,Guo, Huiyuan,Lu, Yu
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p. 117 - 125
(2017/06/05)
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- A method for the production of primary amines
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The invention relates to the field of chemical industry and particularly relates to a method for preparing primary amine by using the raw materials including halogenated hydrocarbon (or hydrocarbon alcohol sulfonate) and ammonia water (or formamide). The method comprises the following three steps: (1) imidization: 3,4-diarylfuran-2,5-diketone (I) reacts with ammonia (or formamide) and the like to obtain 3,4-diaryl-1H-pyrrole-2,5-diketone (II); (2) N-hydrocarbylation: 3,4-diaryl-1H-pyrrole-2,5-diketone (II) generates an N-hydrocarbylation reaction with halogenated hydrocarbon (or hydrocarbon alcohol sulfonate) in the presence of alkali to obtain N-hydrocarbyl-3,4-diaryl-1H-pyrrole-2,5-diketone (III); and (3) hydrolysis: N-hydrocarbyl-3,4-diaryl-1H-pyrrole-2,5-diketone (III) is subjected to alkali hydrolysis to obtain primary amine and the generated 2,3-diaryl maleate is subjected to acid treatment and automatic ring closing to form 3,4-diaryl furan-2,5-diketone (I) which is subjected to imidization and directly applied to the N-hydrocarbylation reaction. The method provided by the invention has the characteristics that the 3,4-diaryl furan-2,5-diketone can be circularly used at a high recovery rate, the molar ratio of the raw materials is low, and the yield of the product primary amine is high.
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Paragraph 0237; 0307
(2016/10/09)
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- An Iodine-Catalyzed Hofmann-L?ffler Reaction
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Iodine reagents have been identified as economically and ecologically benign alternatives to transition metals, although their application as molecular catalysts in challenging C-H oxidation reactions has remained elusive. An attractive iodine oxidation catalysis is now shown to promote the convenient conversion of carbon-hydrogen bonds into carbon-nitrogen bonds with unprecedented complete selectivity. The reaction proceeds by two interlocked catalytic cycles comprising a radical chain reaction, which is initiated by visible light as energy source. This unorthodox synthetic strategy for the direct oxidative amination of alkyl groups has no biosynthetic precedence and provides an efficient and straightforward access to a general class of saturated nitrogenated heterocycles.
- Martínez, Claudio,Mu?iz, Kilian
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supporting information
p. 8287 - 8291
(2015/07/07)
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- Synthesis and antitumor activity of 5-(5-halogenated-2-oxo-1H-pyrrolo[2,3-b]pyridin-(3Z)-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamides
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We report herein the design and synthesis of a series of novel 5-halogenated-7-azaindolin-2-one derivatives containing a 2,4-dimethylpyrrole moiety. Nine target compounds with ≥70% inhibition against MCF-7 at 30 μM were further evaluated for their in vitro antitumor activity against seven human cancer cell lines by SRB assay. Results reveal that some compounds have potent antitumor activity, and the most active 13c7 (IC50s: 4.49-15.39 μM) was found to be more active than Sunitinib (IC50s: 4.70->30 μM) against all of the tested cancer cell lines.
- Wang, Minghua,Ye, Cheng,Liu, Mingliang,Wu, Zhaoyang,Li, Linhu,Wang, Chunlan,Liu, Xiujun,Guo, Huiyuan
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p. 2782 - 2787
(2015/06/08)
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- Development of synthetic routes, via a tropinone intermediate, to a long-acting muscarinic antagonist for the treatment of respiratory disease
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This contribution describes the development of two synthetic routes to an investigational muscarinic antagonist for the treatment of chronic obstructive pulmonary disease. The first route used a starting material which was in plentiful supply within the GSK network and was used to make material for early clinical trials and safety assessment studies. Further investigations identified a second, potential long-term manufacturing route from commercially available building blocks, using substrate control to install the two stereocentres with excellent selectivity. A key step was a substrate-directed epoxide reduction which also gave rise to a minor byproduct through a skeletal rearrangement of the tropane ring. A deuterium-labeling experiment was carried out, which shed light on the origin of the byproduct, and also guided the improvement of reaction conditions.
- Bream, Robert N.,Hayes, Doug,Hulcoop, David G.,Whiteman, Alexandra J.
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p. 641 - 650
(2013/06/27)
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- Synthesis and characterization of picket porphyrin receptors that bind phosphatidylglycerol, an anionic phospholipid found in bacterial membranes
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The lipid binding ability of four urea-picket porphyrins designed to bind to both the phosphate anion portion as well as the glycerol hydroxyl groups of phosphatidylglycerol (PG) has been investigated. Isothermal titration calorimetry (ITC) and 1H NMR were used to determine the receptor's stoichiometry of binding, association constants, and both the enthalpy and entropy of binding with the PG anion. Spectral evidence shows that the phosphate anion portion of PG is hydrogen bonded to the urea groups of the receptors. This binding interaction orients the PG anion in the receptor pocket such that its glycerol hydroxyl groups can align with a third urea picket, and results are furnished that suggest this multifunctional interaction does occur. The structure of the entire picket was found to influence the enthalpy and entropy of lipid binding. The synthesis of tetrabutlyammonium phosphatidylglycerol (TBAPG), and a detailed spectral characterization of its headgroup, is also presented.
- Alliband, Amanda,Meece, Frederick A.,Jayasinghe, Champika,Burns, Dennis H.
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p. 356 - 362
(2013/02/26)
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- SELECTIVE GLYCOSIDASE INHIBITORS AND USES THEREOF
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The invention is directed to compounds for selectively inhibiting glycosidases, uses of the compounds and pharmaceutical compositions including the compounds, and methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, and/or accumulation or deficiency of O-GlcNAc.
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Page/Page column 142
(2012/05/31)
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- PYRANO[3,2-D]THIAZOL DERIVATIVES AND USES THEREOF AS SELECTIVE GLYCOSIDASE INHIBITORS
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Pyrano[3,2-d]thiazol derivatives of formula (I) for selectively inhibiting glycosidases, uses of the compounds and pharmaceutical compositions including the compounds are disclosed. Methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc are also provided.
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Page/Page column 142; 143
(2012/05/31)
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- Anti-infective compounds
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The present invention relates to small molecule compounds and their use in the treatment of bacterial infections, in particular Tuberculosis.
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Page/Page column 14
(2011/08/04)
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- 2-AMINO-PYRIDINE DERIVATIVES AS BETA-2 ADRENORECEPTOR AGONISTS
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The invention relates to compounds of formula (1) and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such derivatives. The compounds according to the present invention are useful in
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- Nitroxyl (HNO) release from new functionalized N-hydroxyurea-derived acyl nitroso-9,10-dimethylanthracene cycloadducts
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A thermal retro-Diels-Alder decomposition of N-hydroxyurea-derived acyl nitroso compounds and 9,10-dimethylanthracene cycloadducts followed by acyl nitroso compound hydrolysis produces nitrous oxide, evidence for the formation of nitroxyl, the one-electron reduced form of nitric oxide that has drawn considerable attention for its potential roles in biological systems. EPR and NMR spectroscopy provide further evidence for nitroxyl formation and kinetic information, respectively. Such compounds may prove to be useful alternative nitroxyl donors.
- Zeng, Bu-Bing,Huang, Jinming,Wright, Marcus W.,King, S. Bruce
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p. 5565 - 5568
(2007/10/03)
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- Preparation of silk fibroin-supported Pd(0) catalyst for chemoselective hydrogenation: Reduction of palladium(II) acetate by methanol on the protein
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The Pd/fibroin (Fib) was easily prepared by the auto-reduction of the silk-fibroin conjugated Pd(OAc)2 using MeOH as a solvent and a reductant and exhibited good chemoselectivity in the hydrogenation of olefins and azides in the presence of aromatic carbonyls and/or halogens or an O-benzyl protective group.
- Sajiki, Hironao,Ikawa, Takashi,Yamada, Hiromi,Tsubouchi, Kozo,Hirota, Kosaku
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p. 171 - 174
(2007/10/03)
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- Inhibitors of protein tyrosine phosphatase
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The present invention comprises small molecular weight, non-peptidic inhibitors of formulae I-VII of Protein Tyrosine Phosphatase 1 (PTP1) which are useful for the treatment and/or prevention of Non-Insulin Dependent Diabetes Mellitus (NIDDM).
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- Development of dual-acting agents for thromboxane receptor antagonism and thromboxane synthase inhibition. 3. Synthesis and biological activities of oxazolecarboxamide-substituted ω-phenyl-ω-(3-pyridyl)alkenoic acid derivatives and related compounds
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A novel series of oxazolecarboxamide-substituted ω-phenyl-ω-(3- pyridyl)alkenoic acid derivatives was discovered as potent dual-acting agents to block the TXA2 receptor and to inhibit the thromboxane synthase (TRA/TSI). Synthesis, structure-activity relationship (SAR), and in vitro and in vivo pharmacology of this series of compounds are described. Modification of the series revolved around the oxazole moiety to increase the hydrophilicity of the compounds and to correlate the biological activity with lipophilicity of the compounds. The most potent in the series was (E)-7-[4- [4-[[(4-cyclohexylbutyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept- 6-enoic acid (14) with K(d) = 9.9 ± 0.4 nM for the thromboxane receptor antagonism and IC50 = 55.0 ± 17.9 nM for thromboxane synthase inhibition. The compound 14 was a selective TRA/TSI which exhibited desirable characteristics for oral activity, 'shunt' effect to elevate PGI2 level, and absence of agonist activity.
- Takeuchi, Kumiko,Kohn, Todd J.,True, Timothy A.,Mais, Dale E.,Wikel, James H.,Utterback, Barbara G.,Wyss, Virginia L.,Jakubowski, Joseph A.
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p. 5362 - 5374
(2007/10/03)
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- A novel type of Pd/C-catalyzed hydrogenation using a catalyst poison: Chemoselective inhibition of the hydrogenolysis for O-benzyl protective group by the addition of a nitrogen-containing base
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A mild and chemoselective hydrogenation method for a variety of reducible functional groups distinguishing front aliphatic and aromatic' benzyl ethers was accomplished by the addition of an appropriate nitrogen- containing base to the Pd/C-catalyzed hydrogenation system.
- Sajiki, Hironao,Hirota, Kosaku
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p. 13981 - 13996
(2007/10/03)
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- PREPARATION OF SUBSTITUTED ALKENOIC ACIDS
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This invention relates to a highly selective process for preparation of E-ω-phenyl-ω-(3-pyridyl)-ω-alkenoic acid derivatives bearing a carbamoyl substituted oxazolyl or oxazolinyl group on the phenyl ring which demonstrate utility for thromboxane receptor antagonism and/or thromboxane synthase inhibition, as well as to intermediates therefor.
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- The formation of a novel Pd/C-ethylenediamine complex catalyst: Chemoselective hydrogénation without deprotection of the o-benzyl and ZV-Cbz groups
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A Pd/C catalyst formed an isolable complex with ethylenediamine employed as the catalytic poison via one-to-one interaction between Pd metal and ethylenediamine, and this complex catalyst [Pd/ C(en)] chemoselectively hydrogenated a variety of reducible functionalities such as olefin, acetylene, nitro, benzyl ester, and azido in the presence of an O-benzyl or N-Cbz protective group. These findings reinforce the versatility potential of O-benzyl and N-Cbz as protective groups in organic synthesis, and the Pd/C(en) catalyst has been identified as a novel and chemoselective catalyst for the hydrogénation.
- Sajiki, Hironao,Hattori, Kazuyuki,Hirota, Kosaku
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p. 7990 - 7992
(2007/10/03)
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- Indole derivatives as 5-HT1-like agonists for use in migraine
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The present invention relates to 3,5-disubstituted indole compounds which are selective agonists which act on 5-hdroxytryptamine receptors useful in the treatment of migraine.
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- Carbamoyl substituted oxazoles as thromboxane receptor antagonists
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This invention relates to carbamoyl substituted heterocycles which are ω-phenyl-ω-(3-pyridyl)-ω-alkenoic acid derivatives bearing a carbamoyl substituted oxazolyl or oxazolinyl group on the phenyl ring and which demonstrate utility for thromboxane receptor antagonism and/or thromboxane synthase inhibition, as well as pharmaceutical formulations containing them, methods for their use, and processes and intermediates for their preparation.
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- Selective O-benzylation of aminoalkanols
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A simple and one-step method has been developed for selective O-benzylation of aminoalkanols. Study of steric effects shows the best selectivity in adjacent 1°-OH vs 2°-CHNH2 and decreased selectivity in 2°-OH vs 1°-CH2NH2 and non adjacent aminoalkanol.
- Hu,Cassady
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p. 907 - 913
(2007/10/02)
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- Lack of effect of the length of oligoglycine- and oligo(ethylene glycol)-derived para-substituents on the affinity of benzenesulfonamides for carbonic anhydrase II in solution
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Using 1H NMR spectroscopy, values of T2 have been determined for the methylene protons of the oligoglycine moieties of para-substituted benzenesulfonamides having structures H2NO2SC6H4CO(Gly)(n)OH (n = 1-6) bound at the active site of bovine carbonic anhydrase II (CA, EC 4.2.1.1). These values have been correlated with measurements of dissociation constants of these complexes, in order to infer motion of these ligands when bound to the enzyme. Motion of glycines 1-3 (those closest to the aryl ring) is hindered by their proximity to the protein; motion of glycines 4-6 is relatively unhindered. Despite the restriction to motion inferred for glycines 1-3, the values of K(d) for the six compounds (n = 1-6, 1-6) are indistinguishable within experimental uncertainty (± 20%): K(d) in μM (n) 0.30 (1); 0.26 (2); 0.33 (3); 0.37 (4); 0.37 (5); 0.34 (6). There is, therefore, an unexpected compensation of the loss in conformational entropy on binding by another contributor to the free energy.
- Jain, Ahamindra,Huang, Shaw G.,Whitesides, George M.
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p. 5057 - 5062
(2007/10/02)
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- THE USE OF PEARLMAN'S CATALYST FOR SELECTIVE N-DEBENZYLATION IN THE PRESENCE OF BENZYL ETHERS
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Hydrogenation with 20percent palladium hydroxide on carbon seletively removes benzyl groups from amines in high yields without cleaving benzyl ethers.
- Bernotas, Ronald C.,Cube, Rowena V.
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p. 1209 - 1212
(2007/10/02)
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