- Reaction of Diisobutylaluminum Borohydride, a Binary Hydride, with Selected Organic Compounds Containing Representative Functional Groups
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The binary hydride, diisobutylaluminum borohydride [(iBu)2AlBH4], synthesized from diisobutylaluminum hydride (DIBAL) and borane dimethyl sulfide (BMS) has shown great potential in reducing a variety of organic functional groups. This unique binary hydride, (iBu)2AlBH4, is readily synthesized, versatile, and simple to use. Aldehydes, ketones, esters, and epoxides are reduced very fast to the corresponding alcohols in essentially quantitative yields. This binary hydride can reduce tertiary amides rapidly to the corresponding amines at 25 °C in an efficient manner. Furthermore, nitriles are converted into the corresponding amines in essentially quantitative yields. These reactions occur under ambient conditions and are completed in an hour or less. The reduction products are isolated through a simple acid-base extraction and without the use of column chromatography. Further investigation showed that (iBu)2AlBH4 has the potential to be a selective hydride donor as shown through a series of competitive reactions. Similarities and differences between (iBu)2AlBH4, DIBAL, and BMS are discussed.
- Amberchan, Gabriella,Snelling, Rachel A.,Moya, Enrique,Landi, Madison,Lutz, Kyle,Gatihi, Roxanne,Singaram, Bakthan
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supporting information
p. 6207 - 6227
(2021/05/06)
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- GPR40 receptor stimulant, and preparation method, pharmaceutical composition and application thereof
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The invention discloses a GPR40 receptor stimulant, and a preparation method, a pharmaceutical composition and application thereof. The invention particularly discloses a GPR40 receptor stimulant shown in general formula (I) and pharmacologically acceptable salt thereof, a preparation process of the compound, a pharmaceutical composition containing the compound of general formula (I), and application of the compound and the pharmaceutical composition in anti-diabetes.
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Paragraph 0163-0168
(2019/10/15)
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- COMPOUNDS
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Provided are benzoxazolinone sulfonamide derivatives that inhibit Na v1.7 activity, pharmaceutical compositions containing them and their use in therapy for the treatment of diseases mediated by Na v1.7 activity.
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Page/Page column 58
(2018/12/03)
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- Design, synthesis and biological evaluation of a series of novel GPR40 agonists containing nitrogen heterocyclic rings
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A novel series of GPR40 agonists is designed by introducing nitrogen-containing heterocyclic ring at the terminal phenyl ring of TAK-875 with the aim of decreasing its lipophilicity. Three different β-substituted phenylpropionic acids were investigated as the acidic components. A total of 34 compounds have been synthesized, among which, compound 30 exhibited comparable GPR40 agonistic activity in vitro with TAK-875 and relatively lower lipophilicity through calculation (30, EC50 = 1.2 μM, cLogP = 1.3; TAK-875: EC50 = 5.1 μM, cLogP = 3.4). Moreover, compound 30 was able to enhance the insulin secretion of primary islets isolated from normal ICR mice and showed no obvious inhibition against cytochromes P450 in vitro. In vivo, compound 30 exhibited efficacy in oral glucose tolerance test (oGTT) in normal ICR mice.
- Sun, Zhaozhu,Zhou, Tian,Pan, Xuan,Yang, Ying,Huan, Yi,Xiao, Zhiyan,Shen, Zhufang,Liu, Zhanzhu
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supporting information
p. 3050 - 3056
(2018/08/11)
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- Fe3O4-SiO2-P4VP pH-sensitive microgel for immobilization of nickel nanoparticles: An efficient heterogeneous catalyst for nitrile reduction in water
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Fe3O4 magnetic nanoparticles (MNPs) were modified with (3-aminopropyl)triethoxysilane through silanization. An atom transfer radical polymerization-initiating site immobilized onto amine-functionalized Fe3O4 MNPs. The surface-initiated atom transfer radical polymerization of 4-vinylpyridine was then performed in the presence of Fe 3O4-SiO2-Br nanoparticles, which led to the formation of Fe3O4-SiO2-P4VP [P4VP=poly(4-vinylpyridine)] hybrid microgels cross-linked with Fe 3O4 MNPs. Our approach uses polymer microgels as templates for the synthesis of nickel nanoparticles (NiNPs). The tunable properties of synthesized NiNPs@Fe3O4-SiO2-P4VP pH-sensitive microgels were used in the catalytic reduction of aliphatic and aromatic nitriles. Moreover, the catalytic activity of metal nanocomposites that can be modulated by the volume transition of microgel structures with changing pH has been evaluated. TEM, X-ray photoelectron spectroscopy, thermogravimetric analysis, atomic absorption spectroscopy, XRD, UV/Vis spectroscopy, and FTIR spectroscopy were used to characterize the resultant catalyst. Mystery solved: Our approach uses polymer microgels as templates for the synthesis of nickel nanoparticles. The tunable properties of synthesized NiNPs@Fe3O 4-SiO2-P4VP [NiNPs=nickel nanoparticles; P4VP=poly(4-vinylpyridine)] pH-sensitive microgels are used in the catalytic reduction of aliphatic and aromatic nitriles. Moreover, the catalytic activity of metal nanocomposites that can be modulated by the volume transition of microgel structures with changing pH has been evaluated. Copyright
- Nabid, Mohammad Reza,Bide, Yasamin,Niknezhad, Mahvash
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p. 538 - 546
(2014/03/21)
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- Concise copper-catalyzed synthesis of tricyclic biaryl ether-linked aza-heterocyclic ring systems
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A new method for the synthesis of tricyclic biaryl ether-linked ring systems incorporating seven-, eight-, and nine-membered ring amines is presented. In the presence of catalytic quantities of copper(I), readily accessible acyclic precursors undergo an intramolecular carbon-oxygen bond-forming reaction facilitated by a templating chelating nitrogen atom. The methodology displays a broad substrate scope, is practical, and generates rare and biologically interesting tricyclic heteroaromatic products that are difficult to access by other means.
- Mestichelli, Paola,Scott, Matthew J.,Galloway, Warren R. J. D.,Selwyn, Jamie,Parker, Jeremy S.,Spring, David R.
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p. 5448 - 5451
(2013/11/19)
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- Improved protocol for indoline synthesis via palladium-catalyzed intramolecular C(sp2)-H amination
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An efficient method has been developed for the synthesis of indoline compounds from picolinamide (PA)-protected β-arylethylamine substrates via palladium-catalyzed intramolecular amination of ortho-C(sp2)-H bonds. These reactions feature high efficiency, low catalyst loadings, mild operating conditions, and the use of inexpensive reagents.
- He, Gang,Lu, Chengxi,Zhao, Yingsheng,Nack, William A.,Chen, Gong
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supporting information; experimental part
p. 2944 - 2947
(2012/08/28)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Page/Page column 180; 181
(2011/04/14)
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- Reductions of aliphatic and aromatic nitriles to primary amines with diisopropylaminoborane
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Diisopropylaminoborane [BH2Nf)Pr)2] in the presence of a catalytic amount of lithium borohydride (LiBH4) reduces a large variety of aliphatic and aromatic nitriles in excellent yields. BH 2NOPr)2 can be prepared by two methods: first by reacting diisopropylamineborane [(iPr)2N)BH3] with 1.1 equiv of n-butylhthium (n-BuLi) followed by methyl iodide (MeI), or reacting iPrN:BH 3 with 1 equiv of n-BuLi followed by trimethylsilyl chloride (TMSCl). BH2N(ZPr)2 prepared with MeI was found to reduce benzonitriles to the corresponding benzylamines at ambient temperatures, whereas diisopropylaminoborane prepared with TMSCl does not reduce nitriles unless a catalytic amount of a lithium ion source, such as LiBH4 or lithium tetraphenylborate (LiBPh4), is added to the reaction. The reductions of benzonitriles with one or more electron-withdrawing groups on the aromatic ring generally occur much faster with higher yields. For example, 2,4-dichlorobenzonitrile was successfully reduced to 2,4-dichlorobenzylamine in 99% yield after 5 h at 25 °C. On the other hand, benzonitriles containing electron-donating groups on the aromatic ring require refluxing in tetrahydrofuran (THF) for complete reduction. For instance, 4- methoxybenzonitrile was successfully reduced to 4-methoxybenzylamine in 80% yield. Aliphatic nitriles can also be reduced by the BH2N(iPr) 2/cat. LiBH4 reducing system. Benzyl cyanide was reduced to phenethylamine in 83% yield. BH2NOPr)2 can also reduce nitriles in the presence of unconjugated alkenes and alkynes such as the reduction of 2-hexynenitrile to hex-5-yn-l-amine in 80% yield. Unfortunately, selective reduction of a nitrile in the presence of an aldehyde is not possible as aldehydes are reduced along with the nitrile. However, selective reduction of the nitrile group at 25 °C in the presence of an ester is possible as long as the nitrile group is activated by an electron-withdrawing substituent. It should be pointed out that lithium aminoborohydrides (LABs) do not reduce nitriles under ambient conditions and behave as bases with aliphatic nitriles as well as nitriles containing acidic a-protons. Consequently, both LABs and BH2NOPr)2 are complementary to each other and offer methods for the selective reductions of multifunctional compounds.
- Haddenham, Dustin,Pasumansky, Lubov,DeSoto, Jamie,Eagon, Scott,Singaram, Bakthan
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experimental part
p. 1964 - 1970
(2009/07/01)
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- Lewis acid-catalyzed intramolecular amination via 1,3-chirality transfer
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Direct intramolecular amination of the chiral non-racemic allylic alcohol 1 conjugated with a benzene ring afforded the tetrahydroisoquinoline 2 possessing a newly formed alkene in the presence of a catalytic amount of Lewis acid.
- Kawai, Nobuyuki,Abe, Ryuzou,Uenishi, Jun'Ichi
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scheme or table
p. 6580 - 6583
(2011/02/23)
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- The endocyclic restriction test: The geometries of nucleophilic substitutions at sulfur(VI) and sulfur(II)
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(Chemical Equation Presented) The trajectories for nucleophilic substitutions at sulfur(VI) and sulfur(II) have been investigated by the endocyclic restriction test. On the basis of double-labeling experiments, the sulfur(VI) transfer in the conversion of 1 to 2 is found to be intramolecular, while the sulfur(VI) transfer in the conversion of 3 to 4 and the sulfur(II) transfer in the conversion of 5 to 6 are found to be intermolecular. These results are taken to be consistent with transition structures for these sulfur transfer reactions which require a large angle between the entering and leaving group, a geometry analogous to apical group positions in trigonal bipyramidal transition states.
- Jarboe, Stephen G.,Terrazas, Michael S.,Beak, Peter
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supporting information; experimental part
p. 9627 - 9632
(2009/04/07)
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- A mild inter- and intramolecular amination of aryl halides with a combination of CuI and CsOAc
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A unique combination of CuI and CsOAc was found to catalyze aryl amination under mild conditions. The reaction takes place at room temperature or at 90 °C with broad functional group compatibility. The intramolecular reaction was able to form five-, six-, and seven-membered rings with various protecting groups on the nitrogen atom. The scope of the intermolecular amination, as well as its applications to unsymmetrical N,N′-dialkylated phenylenediamines, was investigated.
- Kubo, Tetsuji,Katoh, Chiharu,Yamada, Ken,Okano, Kentaro,Tokuyama, Hidetoshi,Fukuyama, Tohru
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supporting information; experimental part
p. 11230 - 11236
(2009/04/11)
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- An improved stereocontrolled route to cis-erythrinanes by combined intramolecular Strecker and Bruylants reaction
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Condensation of (2-iodophenyl)ethylamines with cyclohexanoylacetaldehyde provided the corresponding aldimines which were reduced yielding secondary phenethylcyclohexanoylethylamines. These in turn were appropriate intermediates to prepare several erythrin
- Reimann, Eberhard,Ettmayr, Christian
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p. 1143 - 1155
(2007/10/03)
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- Substituted 2-dialkylaminoalkylbiphenyl derivatives
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Substituted 2-dialkylaminoalkylbiphenyl derivatives, processes for their preparation, pharmaceutical compositions comprising these compounds and methods using these compounds for the preparation of medicaments and for the treatment of diseases.
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- Histidine-(N-benzyl glycinamide) inhibitors of protein farnesyl transferase
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Inhibitors of protein farnesyl transferase enzymes are described, as well as methods for the preparation and pharmaceutical compositions of the same, which are useful in treating cancer, restenosis, psoriasis, endometriosis, atherosclerosis, or viral infe
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- The development of efficient protocols for the palladium-catalyzed cyclization reactions of secondary amides and carbamates
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(equation presented) With the proper choice of palladium catalyst, ligand, and base, five-, six-, and seven-membered rings are formed efficiently from secondary amide or secondary carbamate precursors, offering significant improvements to currently existing methodology.
- Yang, Bryant H.,Buchwald, Stephen L.
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- Formation of a carbon-nitrogen bond via a 5-exo-trig radical cyclization onto the nitrogen of an imidate ester
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Intramolecular addition of an aryl radical to the nitrogen of an imidate ester cyclized in the 5-exo-trig mode to form the C-N bond, with no 6-endo- trig product being detected.
- McClure, Cynthia K.,Kiessling, Anthony J.,Link, Jeffrey S.
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p. 7121 - 7126
(2007/10/03)
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- Intramolecular palladium-catalyzed aryl amination and aryl amidation
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Upon treatment with a palladium catalyst and a suitable base, aromatic halides undergo intramolecular substitution to form five, six, and seven-membered rings. In a similar fashion aryl halides with pendant amides or sulfonamides are cyclized to form five and six-membered rings.
- Wolfe, John P.,Rennels, Roger A.,Buchwald, Stephen L.
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p. 7525 - 7546
(2007/10/03)
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- Free-Radical Chemistry of Imines
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Aryl radicals bearing an aldimino functional group as part of an ortho substituent cyclized by addition to C and/or N of the imino group.When the choice was between 5-exo closure to C and 6-endo closure to N, the former predominated.However, 6-endo closure to C predominated over 5-exo cyclization to N in isomeric imines.Absolute values of cyclization rate constants were determined and an explanation for the unusual 6-endo preference is offered.Chiral induction in 6-endo cyclization to C of an aldimine from D-glyceraldehyde acetonide was observed, and its sense was determined.
- Tomaszewski, Miroslaw J.,Warkentin, John,Werstiuk, Nick H.
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p. 291 - 322
(2007/10/02)
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- Schiff Bases as External and Internal Electrophiles in Reactions of Functionalized Organolithium Reagents. A New Route to Isoindoline Derivatives and 1,2,3,4-Tetrahydroisoquinolines
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Reaction of Schiff bases with certain functionalized organolithium reagents is useful in the synthesis of 1,2-diarylisoindolines and 2,3-diarylphthalimidines.Schiff bases derived from 2-(2-bromophenyl)ethylamines on halogen-metal exchange with butyllithium undergo a Parham-type cyclization to yield 1-aryl-1,2,3,4-tetrahydroisoquinolines.
- Bradsher, Charles K.,Hunt, David A.
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p. 327 - 330
(2007/10/02)
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