- Reaction of 1,3-dioxanes with acetone cyanohydrin
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The reaction of 4-phenyl- and 4,4-dimethyl-1,3-dioxanes with acetone cyanohydrin leads to hydrolytically unstable 2-(1-hydroxy-1-methylethyl)-5,6-dihydro-1,3-oxazines, which are readily saponified in alkaline medium to the corresponding 1,3-amino alcohols
- Kuznetsov,Brusilovskii
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Read Online
- Site-Specific C(sp3)–H Aminations of Imidates and Amidines Enabled by Covalently Tethered Distonic Radical Anions
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The utilization of N-centered radicals to synthesize nitrogen-containing compounds has attracted considerable attention recently, due to their powerful reactivities and the concomitant construction of C?N bonds. However, the generation and control of N-centered radicals remain particularly challenging. We report a tethering strategy using SOMO-HOMO-converted distonic radical anions for the site-specific aminations of imidates and amidines with aid of the non-covalent interaction. This reaction features a remarkably broad substrate scope and also enables the late-stage functionalization of bioactive molecules. Furthermore, the reaction mechanism is thoroughly investigated through kinetic studies, Raman spectroscopy, electron paramagnetic resonance spectroscopy, and density functional theory calculations, revealing that the aminations likely involve direct homolytic cleavage of N?H bonds and subsequently controllable 1,5 or 1,6 hydrogen atom transfer.
- Fang, Yuanding,Fu, Kang,Shi, Lei,Zhao, Rong,Zhou, Jia
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p. 20682 - 20690
(2020/09/07)
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- Base-induced Sommelet–Hauser rearrangement of N-(α-(2-oxyethyl)branched)benzylic glycine ester-derived ammonium salts via a chelated intermediate
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The base-induced Sommelet–Hauser (S–H) rearrangement of N-(α-branched)benzylic glycine ester-derived ammonium salts 1 was investigated. When the α-branched substituent was a simple alkyl, such as a methyl or butyl, desired S–H rearrangement product 2 was obtained in low yield with formation of the [1,2] Stevens rearranged 4 and Hofmann eliminated products 5 and 6. However, when the α-branched substituent had a 2-oxy moiety, such as 2-acetoxyethyl or 2-benzoyloxyethyl, the yields of 2 were improved. These results could be explained by formation of chelated intermediate C that stabilizes the carbanionic ylide, and the subsequent initial dearomative [2,3] sigmatropic rearrangement would be accelerated. The existence of C was supported by mechanistic experiments. This enhancement effect is not very strong or effective; however, it will expand the synthetic usefulness of ammonium ylide rearrangements.
- Baba, Souya,Hirano, Kazuki,Tayama, Eiji
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- Method for preparing amino alcohol compound by using halogenated intermediate
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The invention discloses a method for preparing an amino alcohol compound by utilizing a halogenated intermediate. According to the method, an oxygen-halogen bond can be prepared by utilizing cyclic diacyl peroxide and halogenated salt under an illumination condition, and the oxygen-halogen bond is prone to homolysis under an illumination condition to form an active free radical, so the amino alcohol is finally prepared. The novel method for synthesizing the amino alcohol is high in atom utilization rate, simple in synthesis method and high in yield, so the consumption of halide for reactions with synthesis values is reduced, and the purposes of environmental protection and green chemistry are better achieved.
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- COMPOUNDS AND USES THEREOF
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The present invention features compounds useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.
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Paragraph 1222
(2019/11/11)
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- Lipophilic NHC assisted one-pot synthesis of syncarpamide analogues in aqueous medium
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Lipophilic NHC catalysis in aqueous medium was reported for the synthesis of biologically relevant (a)symmetrically substituted and unsymmetrically substituted syncarpamide analogues. All the reported reactions were performed in the absence of any expensive metal salts or additives. A diverse array of syncarpamide analogues was obtained in good yields. Lipophilic NHC catalysis was also extended to chemoselective transesterification reactions.
- Suresh, Pavithira,Selva Ganesan, Subramaniapillai
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p. 6257 - 6261
(2019/04/25)
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- Synthesis, separation-purification, and salt forming method of dapoxetine
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The invention provides a novel synthesis, gradient separation-purification, and salt forming method of dapoxetine. Easily available and cheap benzaldehyde is taken as the primary raw material of the synthesis route. The whole reaction conditions are mild. The synthesis route is short. No highly toxic or explosive raw material is used. The problem of chiral separation is well solved in the route. During the separation process, the product is purified. Finally, chlorinated hydromethyl tert-butyl ether which does not have any side or toxic effect is used to carry out salt forming. A large amount of labor, material, and time is saved. The production cost is reduced. The synthesis does not need any special equipment. The operation is simple and convenient. The method has a good industrial application prospect.
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- A S - west reaches anchors the sandbank and its salt synthesis method
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The invention discloses a synthetic method for S-dapoxetine. The synthetic method comprises the following steps: (1) resolving 1-phenyl-3-(naphthyl-1-oxy)propylamine for at least once with a resolving agent to obtain a resolved mixed system; (2) separating the resolved mixed system to obtain S-1-phenyl-3-(naphthyl-1-oxy)propylamine, and recycling mother liquor; (3) performing methylation on the S-1-phenyl-3-(naphthyl-1-oxy)propylamine to obtain S-dapoxetine. Compared with the conventional industrial production method, residual intermediate (R)-phenyl-3-(naphthyl-1-oxy)propylamine in the resolved mother liquor is firstly recycled on the basis of the prior art, then resolved again through D-(-) tartaric acid after racemization, and recycled, so that the yield is increased, the product waste is avoided, and the economic benefits are improved.
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- Synthesis and biological evaluation of novel piperidin-4-ol derivatives
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A series of novel piperidin-4-ol derivatives were designed, synthesized, and evaluated for potential treatment of HIV. The compounds were obtained via an efficient synthetic route in excellent yields and have been characterized by 1H NMR, 13C NMR, MS, and elemental analysis. The CCR5 antagonistic activities of the compounds have also been evaluated.
- Weng, Zhiyong,Wei, Wei,Dong, Xiaowu,Hu, Yongzhou,Huang, Shufang,Liu, Tao,Xie, Xin
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scheme or table
p. 303 - 308
(2012/07/03)
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- PROCESSES FOR THE PREPARATION OF (+)-N,N-DIMETHYL-2-[1-(NAPHTHALENYLOXY) ETHYL] BENZENE METHANAMINE AND INTERMEDIATES THEREOF
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The present invention relates to processes for the preparation of S(+)-N,N-dimethyl-2-[1-(naphthalenyloxy)ethyl]benzene methanamine and intermediates thereof. More particularly the present invention relates to preparation of the compound 3(S)-(+)-N,N-dimethylamino-3-phenyl propanol useful as intermediate in the synthesis of pharmaceutically active compounds.
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Page/Page column 24
(2012/01/13)
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- Synthesis of heterocycles through a ruthenium-catalyzed tandem ring-closing metathesis/isomerization/N-acyliminium cyclization sequence
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Tandem bicycle: In the title reaction double bonds created during ring-closing metathesis isomerize to generate reactive iminium intermediates that undergo intramolecular cyclization reactions with tethered heteroatom and carbon nucleophiles. In this way, a series of biologically interesting heterocyclic compounds can be made, including a known precursor for the total synthesis of the antiparasitic natural product harmicine. Copyright
- Ascic, Erhad,Jensen, Jakob F.,Nielsen, Thomas E.
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supporting information; experimental part
p. 5188 - 5191
(2011/06/26)
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- Efficient and regioselective synthesis of 5-hydroxy-2-isoxazolines: Versatile synthons for isoxazoles, β-lactams, and γ-amino alcohols
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"Chemical Equation Presented" An efficient and highly regioselective protocol was developed for the preparation of 5-hydroxy2-isoxazolines, which have been proved to be versatile synthons for isoxazles, β-hydroxy oximes, and γ-amino alcohols. β-Lactams, commonly embedded in the skeletons of bioactive natural products, were also synthesized in two steps from β-hydroxy oximes, providing a new strategy for the synthesis of this kind of compounds.
- Tang, Shibing,He, Jinmei,Sun, Yongquan,He, Liuer,She, Xuegong
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supporting information; experimental part
p. 1961 - 1966
(2010/06/20)
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- Novel phosphorus-containing prodrug
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Novel cyclic phosphoramidate prodrugs of parent drugs MH of formula I their use in delivery of drugs to the liver, their use in enhancing oral bioavailability, and their method of preparation are described.
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Page/Page column 66
(2010/11/08)
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- Lipase-catalyzed resolution of chiral 1,3-amino alcohols: application in the asymmetric synthesis of (S)-dapoxetine
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The enzymatic resolution of 3-amino-3-phenylpropan-1-ol derivatives has been studied through acylation processes. Candida antarctica lipase A (CAL-A) has been identified as the best biocatalyst for the transesterification reaction of 3-amino-3-phenyl-1-tert-butyldimethylsilyloxy-propan-1-ol using ethyl methoxyacetate as acylating agent and tert-butyl methyl ether as solvent. This enzymatic study has allowed us to obtain a valuable intermediate for the production of (S)-dapoxetine, which has been synthesized in good overall yield and high enantiomeric excess.
- Torre, Oliver,Gotor-Fernandez, Vicente,Gotor, Vicente
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p. 860 - 866
(2007/10/03)
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- Preparation of enantiomerically pure (R)- and (S)-3-amino-3-phenyl-1- propanol via resolution with immobilized penicillin G acylase
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Ethyl 2,4-dioxo-4-phenylbutyrate, obtained by condensation of acetophenone with diethyl oxalate, was converted to 3-oxo-3-phenyl-1-propanol in 90% yield by reaction with baker's yeast. Reductive amination with sodium cyanoborohydride in the presence of ammonium acetate gave the racemic 3-amino-3-phenyl-1-propanol in 65% yield. Enzymatic resolution of the corresponding N-phenylacetyl derivative with penicillin G acylase, immobilized on an epoxy resin gave (S)-amide and (R)-amino alcohol in high enantiomeric purity (ee >99%) and >45% yields for each enantiomer.
- Fadnavis, Nitin W.,Radhika, Kasiraman R.,Vedamayee Devi
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p. 240 - 244
(2007/10/03)
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- Structure-activity relationships of 1,3,5-triazine-2,4,6-triones as human gonadotropin-releasing hormone receptor antagonists
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SAR studies of 1,3,5-triazine-2,4,6-triones as human gonadotropin-releasing hormone receptor antagonists resulted in potent compounds. The best compound from the series had a binding affinity of 2 nM.
- Guo, Zhiqiang,Wu, Dongpei,Zhu, Yun-Fei,Tucci, Fabio C.,Regan, Collin F.,Rowbottom, Martin W.,Struthers, R. Scott,Xie, Qiu,Reijmers, Shelby,Sullivan, Susan K.,Sai, Yang,Chen, Chen
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p. 3685 - 3690
(2007/10/03)
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- TUBULIN INHIBITORS
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Compounds of general formula (I), (II) (III) and (V) are described for use in modulating microtubule polymerisation and in the treatment of associated disease states. Use of compounds (I), (III) and (V) in the treatment of kinase-associated disease states is also described. Further described are novel compounds of formula (II), (III) and (V).
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Page/Page column 42
(2008/06/13)
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- A convenient synthesis of dihydro- and tetrahydro-1,3-thiazine derivatives from β-aryl-β-amino acids
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A facile synthesis of 2-alkyl-4-aryl-5,6-dihydro-4H-1,3-thiazines and cis-2-alkyl-4-aryl-3,4,5,6-tetrahydro-2H-1,3-thiazines with potential therapeutic interest was achieved starting from readily accessible β-aryl-β-amino acids.
- Leflemme, Nicolas,Dallemagne, Patrick,Rault, Sylvain
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p. 1503 - 1505
(2007/10/03)
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- PYRAZINE-BASED TUBULIN INHIBITORS
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A compound of general formula (I) or pharmaceutically acceptable prodrugs, salts, hydrates, solvates, crystal forms or diastereomers thereof is described. A method of treating a hyperproliferation-related disease state or disorder in a subject using a compound of formula (I) is also described
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- Dutch Resolution: Separation of enantiomers with families of resolving agents. A status report
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Dutch Resolution is the term given to the use of mixtures (families) of resolving agents in classical resolutions. In this status report an overview is given of the latest results and new (possible) families of resolving agents are introduced. The concept of families is discussed as well as the factors that come into play on use of families. Practical aspects of Dutch Resolution in particular and resolutions in general are discussed.
- Kellogg, Richard M.,Nieuwenhuijzen, Jose W.,Pouwer,Vries, Ton R.,Broxterman, Quirinus B.,Grimbergen, Reinier F.P.,Kaptein, Bernard,La Crois, Rene M.,De Wever, Ellen,Zwaagstra, Karen,Van Der Laan, Alexander C.
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p. 1626 - 1638
(2007/10/03)
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- Studies on the asymmetric reduction of β-oximino methyl ether boronates: Reagent control, double diastereocontrol and transmitted remote asymmetric induction
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High asymmetric induction (94% ee) could be obtained in the reduction of the achiral E-oxime ether boronate 5 with a homochiral oxazaborolidine 13-BH3-THF complex. Application of this homochiral reducing agent system to non-aromatic oxime ethers 21 produced low to moderate asymmetric induction. Application of the same homochiral reducing agent system to reduction of homochiral boronate E-oximes 3 and 4 produced extreme double diastereo-selection effects, i.e. 8 and 95% ee respectively, which demonstrated that remote asymmetry was being 'transmitted' by a suitable choice of a 'partner' molecule from the boronate moiety to the oxime during reduction. However, attempts to obtain direct remote asymmetric induction in the reduction of homochiral β-oximino boronate methyl ethers 3 and 4 to the corresponding amines produced zero, with for example BH3-THF complex, up to 28% ee with an Et3N-BH3-THF mixture (after oxidative boronate ester cleavage).
- Sailes, Helen E.,Watts, John P.,Whiting, Andrew
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p. 3362 - 3374
(2007/10/03)
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- Synthesis, X-ray crystal-structure analysis, and NMR studies of (η3- allyl)palladium(II) complexes containing a novel dihydro(phosphinoaryl)oxazine ligand: Application in palladium-catalyzed asymmetric synthesis
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The novel chiral P,N-ligand 2-[2-(diphenylphosphino)phenyl]-5,6-dihydro- 4-phenyl-4H-1,3-oxazine (4) was synthesized. The corresponding {dihydro[(phosphino-κP)aryl]oxazine-κN} (η3-diphenylallyl)palladium(II) hexafluorophosphate 5 and the analogous [Pd(η3-1,3-dimethylallyl)] complex 6 were investigated by X-ray analysis and 1D- and 2D-NMR spectroscopy. The complex 5 exists as 'exo'-syn-syn isomer in the solid state (Fig. 1). In solution, the same isomer exceeds with 90%. The X-ray crystal structure of 6 reveals that the dihydro(phosphinoaryl)oxazine ligand coordinates in a pseudo-enantiomeric conformation compared with that of 5 (Fig. 3). A syn-anti arrangement of the allyl substituents of 6 is favored in the solid state. 1H-NMR Spectroscopic investigations suggest that the auxiliary 6 adopts two conformations. This conformational instability together with 'exo'/'endo' and syn/anti isomerization leads to the formation of 6 isomers (Fig. 4). The asymmetric allylic substitution reaction of 1,3-diphenylallyl acetate with dimethyl malonate in the presence of 4 proceeds with a selectivity of 99% ee. The ee induced by 4 in the catalytic allylic substitution of 1-methylbut-2- enyl acetate is moderate (54%).
- Liu, Shuangying,Mueller, Juergen F. K.,Neuburger, Markus,Schaffner, Silvia,Zehnder, Margareta
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p. 1256 - 1267
(2007/10/03)
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- Oxazolidinones as alpha 1A receptor antagonists
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This invention is directed to oxazolidinone compounds which are selective antagonists for human alpha 1A receptors. This invention is also related to uses of these compounds for lowering intraocular pressure, inhibiting cholesterol synthesis, relaxing lower urinary tract tissue, the treatment of benign prostatic hyperplasia, impotency, cardiac arrhythmia and for the treatment of any disease where the antagonism of the alpha 1A receptor may be useful. The invention further provides a pharmaceutical composition comprising a therapeutically effective amount of the above-defined compounds and a pharmaceutically acceptable carrier.
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- Regiospecific Opening of Oxetanes with Trimethylsilyl Cyanide - Zinc Iodide. A General Approach to γ-Amino Alcohols.
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Trimethylsilyl ethers of γ-hydroxy isonitriles were formed regiospecifically in the opening of oxetanes with trimethylsilyl cyanide - zinc iodide.Deprotection and hydrolysis of the initially formed ring cleavage products gave γ-amino alcohols.
- Gassman, Paul G.,Haberman, Leonard M.
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p. 4971 - 4974
(2007/10/02)
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- ADDITION OF NITRILES TO OXETANES
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The reaction of oxetanes with acrylonitrile and benzonitrile in the presence of concentrated sulfuric acid leads to the formation of the corresponding 5,6-dihydro-1,3-oxazines.
- Pavel', T. M.
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p. 157 - 159
(2007/10/02)
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- Synthesis via Isoxazolines, 5. - 1,3-Asymmetric Induction in the reduction of 3,5-Disubstituted 2-Isoxazolines; Diastereoselective Synthesis and Configurational Assignment of γ-Amino Alcohols
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The cycloaddition of nitrile oxides to alkenes, followed by reduction of the ensuing 2-isoxazolines 3, yields γ-amino alcohols 4 in a regioselective manner.The stereoselectivity of the reduction step is examined; it is highest with LiAlH4 as the reducing agent. 1,3-Asymmetric induction by isoxazoline ring substituents leads to β-4:α-4 ratios of ca. 85:15 for 5-methyl and ca. 95:5 for 5-phenyl. (CH3)2S-BH3, less selectively, furnishes 60:40, Na-Hg and Na/ethanol reduction give rise to 40:60 diastereomer mixtures.From these, two amino alcohols of the α-series are isolated. 3a is reduced by NaBH3CN to give cis/trans-isoxazolines 11. - The relative configurations of β- and α-4 and, consequently, the steric course of these reductions, are established by 1H- and 13C-NMR studies of 4 as well as of cyclic derivatives (azetidine 7, tetrahydro-1,3-oxazine 10).In addition, conformations of the free amino alcohols 4 are suggested on the basis of 13C-NMR data.
- Jaeger, Volker,Buss, Volker
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p. 101 - 121
(2007/10/02)
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