- Attempt to Synthesize Hindered 2,4,6-Tri-Aryloxy-s-Triazines: Bis(2,4-di-tert-Butylphenyl) Carbonate – Crystal Structure
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Some less hindered 2,4,6-tri-aryloxy-s-triazines were synthesized through the reaction of the corresponding phenols as a starting materials with cyanogen bromide (BrCN) to obtain the corresponding arylcyanates and then trimerized. Unexpectedly, 2,4-di-tert-butyl-1-cyanatobenzene derived from 2,4-di-tert-butylphenol did not trimerize but, indeed, yielded bis(2,4-di-tert-butylphenyl) carbonate. The structures of 2,4,6-tri-aryloxy-s-triazines and bis(2,4-di-tert-butylphenyl) carbonate were characterized by means of IR, 1H, and 13C NMR spectroscopies. Also the structure of the latter compound was studied by X-ray crystallography.
- Noroozi Pesyan, Nader,Kashani, Elmira,Ghorbanzadeh, Kamaleh,Notash, Behrouz
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- Highly Enantioselective α-Cyanation with 4-Acetylphenyl Cyanate
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A highly effective asymmetric version of α-cyanation of β-keto esters and amides was developed with a Lewis-acid catalyst. Thus, by using 10 mol % of a tridentate bisoxazoline–zinc(II) complex as the catalyst, a series of chiral nitriles containing a quaternary carbon center were obtained in excellent enantioselectivities (up to 97 % enantiomeric excess) and up to 95 % yield in the presence of 4 ? molar sieve at room temperature. For the first time, mild and active 4-acetylphenyl cyanate was used instead of cyano-hyperiodinate as the cationic cyano source for catalytic asymmetric α-cyanation.
- Qiu, Jia-Shen,Wang, Yao-Feng,Qi, Gui-Rong,Karmaker, Pran G.,Yin, Hong-Quan,Chen, Fu-Xue
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- Discovery of Fragment-Derived Small Molecules for in Vivo Inhibition of Ketohexokinase (KHK)
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Increased fructose consumption and its subsequent metabolism have been implicated in hepatic steatosis, dyslipidemia, obesity, and insulin resistance in humans. Since ketohexokinase (KHK) is the principal enzyme responsible for fructose metabolism, identification of a selective KHK inhibitor may help to further elucidate the effect of KHK inhibition on these metabolic disorders. Until now, studies on KHK inhibition with small molecules have been limited due to the lack of viable in vivo pharmacological tools. Herein we report the discovery of 12, a selective KHK inhibitor with potency and properties suitable for evaluating KHK inhibition in rat models. Key structural features interacting with KHK were discovered through fragment-based screening and subsequent optimization using structure-based drug design, and parallel medicinal chemistry led to the identification of pyridine 12.
- Huard, Kim,Ahn, Kay,Amor, Paul,Beebe, David A.,Borzilleri, Kris A.,Chrunyk, Boris A.,Coffey, Steven B.,Cong, Yang,Conn, Edward L.,Culp, Jeffrey S.,Dowling, Matthew S.,Gorgoglione, Matthew F.,Gutierrez, Jemy A.,Knafels, John D.,Lachapelle, Erik A.,Pandit, Jayvardhan,Parris, Kevin D.,Perez, Sylvie,Pfefferkorn, Jeffrey A.,Price, David A.,Raymer, Brian,Ross, Trenton T.,Shavnya, Andre,Smith, Aaron C.,Subashi, Timothy A.,Tesz, Gregory J.,Thuma, Benjamin A.,Tu, Meihua,Weaver, John D.,Weng, Yan,Withka, Jane M.,Xing, Gang,Magee, Thomas V.
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- Oxidative rearrangement strategy for synthesis of 2,4,5-trisubstituted oxazoles utilizing hypervalent iodine reagent
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Hypervalent iodine (III)-intermediated direct oxidative rearrangement of 3-hydroxybut-2-enimidates affording oxazoles under mild conditions has been developed. This protocol provides a new methodology to the synthesis of compounds containing oxazole structure.
- Liu, Qing,Zhang, Xiaohui,He, Yang,Hussain, Muhammad Ijaz,Hu, Wen,Xiong, Yan,Zhu, Xiangming
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supporting information
p. 5749 - 5753
(2016/08/30)
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- Nucleophilic imidoesterification of dicarbonyl compounds with cyanatobenzenes through CC bond formation
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Under neat conditions, an efficient method for synthesis of imidoesters has been developed using cyanatobenzenes and dicarbonyl compounds. Nucleophilic addition spontaneously occurred between the two kinds of materials at room temperature with yields of up to 90%. A mechanism directed towards to the imidoester formation has been proposed.
- Ma, Hang,He, Yang,Huang, Ruo-Feng,Zhang, Xiao-Hui,Pan, Jing,Li, Jia-Qiang,He, Chao,Ling, Xue-Ge,Wang, Xuan-Lun,Xiong, Yan
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supporting information
p. 1327 - 1330
(2015/02/19)
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- Synthesis and structure of substituted 5-phenoxy-1,2,4-dithiazole-3-ones
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Seven new substituted 5-phenoxy-1,2,4-dithiazole-3-ones were prepared in modest yield (53-76%) from corresponding O-phenyl thiocarbamates and chlorocarbonylsulfenyl chloride in dry ether at-10 °C. All of the compounds were characterized by NMR and elemental analysis and some of them by X-ray diffraction. Preliminary kinetic measurements showed that the parent 5-phenoxy-1,2,4-dithiazole-3-one is a very efficient sulfurizing agent toward triphenyl phosphite. Copyright
- Ponomarov, Oleksandr,Padelkova, Zdenka,Hanusek, Jiri
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experimental part
p. 1225 - 1228
(2012/01/04)
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- PROCESSES FOR PREPARING JAK INHIBITORS AND RELATED INTERMEDIATE COMPOUNDS
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The present invention is related to processes for preparing chiral substituted pyrazolyl pyrrolo[2,3-d]pyrimidines of Formula III, and related synthetic intermediate compounds. The chiral substituted pyrazolyl pyrrolo[2,3-d]pyrimidines are useful as inhibitors of the Janus Kinase family of protein tyrosine kinases (JAKs) for treatment of inflammatory diseases, myeloproliferative disorders, and other diseases.
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Page/Page column 53
(2010/08/07)
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- Unexpected cyclotrimerization of phenyl cyanate; does Chapman rearrangement occurred in the mass spectrometric ionization of 2,4,6-triphenoxy-1,3,5-S- triazine?
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Unexpected novel cyclotrimerization of phenyl cyanate gave 2,4,6-triphenoxy-1,3,5-s-triazine 3 with excellent yield. No special catalyst is used in this reaction!. The mass spectra of 3 is investigated and it shows some fragments generated by McLafferty and Chapman rearrangements.
- Noroozi-Pesyan, Nader
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p. 329 - 336
(2007/10/03)
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- Unprecedented chemistry of an aryloxychlorodiazirine: Generation of a dihalodiazirine and diazirinone
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The reaction of p-nitrophenoxychlorodiazirine with tetrabutylammonium fluoride follows three channels: (1) ～17% of p-nitrophenoxide/fluoride exchange to chlorofluorodiazirine and p-nitrophenol, (2) ～28% of Cl/F exchange to p-nitrophenoxyfluorodiazirine, and (3) ～55% of ipso fluoride attack, affording p-nitrofluorobenzene and the previously unknown diazirinone (diazacyclopropenone). Copyright
- Moss, Robert A.,Chu, Gaosheng,Sauers, Ronald R.
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p. 2408 - 2409
(2007/10/03)
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- Interaction of aryloxychlorocarbenes with acetylenedicarboxylate: Novel formation of polyfunctional butadienes and 8-oxatricyclo[3.2.1.0 2.4]oct-6-enes
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The interaction of aryloxychlorocarbenes with dialkyl acetylenedicarboxylates has been examined. Thermolyses of 3-aryloxy-3- chlorodiazirines in the presence of acetylenedicarboxylate resulted in the formation of unexpected polyfunctional 1,3-butadienes and 8-oxatricyclo[3.2.1. 02.4]oct-6-enes or of 2-aryoxycarbonylmaleates dependent upon reaction conditions. This work confirmed the nucleophilicity of aryloxychlorocarbenes and underlined their synthetic potential.
- Cheng, Ying,Zhu, Qing,Li, Quan Song,Meth-Cohn, Otto
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p. 4840 - 4846
(2007/10/03)
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- The curtius rearrangement of acyl azides revisited - Formation of cyanate (R-O-CN)
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The Curtius rearrangement is a synthesis of isocyanates (R-N=C=O) by thermal or photochemical rearrangement of acyl acides and/or acylnitrenes. The photochemical rearrangement of benzoyl azide is now shown for the first time to produce a small amount of phenyl cyanate (Ph-O-CN) together with phenyl isocyanate. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.
- Wentrup, Curt,Bornemann, Holger
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p. 4521 - 4524
(2007/10/03)
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- Synthesis of 11-hydroxyl O-methylsterigmatocystin and the role of a cytochrome P-450 in the final step of aflatoxin biosynthesis
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The major skeletal rearrangements (anthraquinone → xanthone → coumarin) that occur in the complex biosynthesis of aflatoxin B1 are mediated by cytochromes P-450. Previous experiments have suggested that two successive monooxygenase reactions are required to convert the xanthone O-methylsterigmatocystin (OMST) to aflatoxin, a process we demonstrate is mediated by a single P-450, OrdA, in Aspergillus parasiticus in accord with findings in A. flavus. The first oxidative cycle is proposed to result in the formation of 11-hydroxy O-methylsterigmatocystin (HOMST), while the second entails aryl ring cleavage, demethylation, dehydration, decarboxylation, and rearrangement to give aflatoxin - a remarkable sequence of transformations. To test this hypothesis, HOMST has been synthesized by an alkylnitrilium variant of the Houben-Hoesch reaction. The troublesome xanthone carbonyl was protected as a butylene to allow further elaboration of the molecule, and then the product xanthone was restored in a uniquely facile peracid deprotection. Methods were devised to construct the sensitive dihydrobisfuran and to maintain the oxidation state of the partially methylated hydroquinone. Expression of ordA in a yeast membrane preparation enabled the intermediacy of HOMST both to be detected in the conversion of OMST to aflatoxin and to be established directly in the biosynthesis of the mycotoxin. Having secured the role of HOMST in aflatoxin formation, the mechanism of the second oxidative cycle of this P-450 is considered.
- Udwary, Daniel W.,Casillas, Linda K.,Townsend, Craig A.
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p. 5294 - 5303
(2007/10/03)
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- Spirocycles
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Spirocycles of the general structural formulae: STR1 wherein: X is O, CH2 or SOm ; R1 is AlkylSO2 NH--, AlkylO--, AlkylSO2 --, AlkylCONH--, or NO2 --; R2 is --H, --OAlkyl, or --Alkyl; R3 is --NHCOCH2 SOm Phenyl, --NHCOCH2 SOm Alkyl, --NHCOC(CH3)2 OH, or NHSO2 Alkyl; R4 and R5 are --H, or --Alkyl; R6 is STR2 R7 is --H, --CN, --NHSO2 Alkyl, --Br, --OAlkyl, --NH2, --NO2, --NHCOAlkyl, or NHCONHAlkyl; R8 is --H, --OH, --CN, --OAlkyl, --CONHAlkyl, --NHSO2 Alkyl, --NHCOAlkyl, --SOm Alkyl, or --CO2 Alkyl; and m is 0-2; or a pharmaceutically acceptable salt, hydrate or crystal form thereof; which are Class III antiarrhythmic agents.
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- NITROGEN-CONTAINING SPIROCYCLES
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Spirocycles of general structural formula: STR1 are Class III antiarrhythmic agents.
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- 2-heteroatom containing urea and thiourea ACAT inhibitors
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The present invention provides N-substituted aryl-N'-heterocyclic substituted ureas and thioureas of the formula STR1 wherein R1, R2 and R3 are hydrogen, fluorine, chlorine, bromine, alkyl, alkoxy, substituted or unsubstituted benzoyl, substituted or unsubstituted phenyl, amino, substituted amino, or a monocyclic heterocyclic, or a carboxy group; and Het is a substituted monocyclic heterocyclic group containing two hetero atoms selected from nitrogen, oxygen or sulfur; which are useful in treating hypercholesterolemia and atherosclerosis.
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- Reactive Nitrogenous Molecules from Meldrum's Acid Derivatives, Pyrrole-2,3-diones, and Isoxazolones
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Flash vacuum pyrolysis of 5-(aminomethylidene)-2,2-dimethyl-1,3-dioxane-4,6-diones (Meldrum's acid derivatives) 12 gives 4-hydroxyquinolines/4-quinolones 15 or 3-enaminoacroleins 22 in good to excellent yields.Intermediate (aminomethylene)ketenes and imidoylketenes are directly observed and their transformation into product 22 monitored by low-temperature IR spectroscopy.Imidoylketenes are also formed and observed upon thermal CO extrusion from pyrrole-2,3-diones 16.Isocyanoamines and fulminates are generated by pyrolysis of hydrazono- or oximino-Meldrum's acid derivatives 32 and 39, monitored by IR spectroscopy, and found to rearrange to cyanamides and cyanates, depending on substituents.The thermal reactions of isoxazol-5(4H)-ones and Meldrum's acid derivatives are compared and discussed.
- Briehl, Horst,Lukosch, Adelheid,Wentrup, Curt
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p. 2772 - 2779
(2007/10/02)
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- Organic Fulminates, R-O-NC
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Organic fulminates are generated by flash vacuum pyrolysis and matrix photolysis of 4-oximinoisoxazol-5(4H)-ones.
- Wentrup, Curt,Gerecht, Bernd,Laqua, Dieter,Briehl, Horst,Winter, Hans-Wilhelm,et al.
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p. 1046 - 1048
(2007/10/02)
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- Cyanic Acid Esters. 29. Bezoxazoline-thione-N-imid Esters and Their Consecutive Reactions
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Oxazoline-thiones-(2) and aryl cyanates react to form the corresponding isoureas 4.These compounds are remarkably stable against electrophilic reagents.The aminolysis of 4 proceeds two pathwais: a transformation of the imid ester residue to the amin and a ring opening reaction by attack of the amin to the C=S-bond.The hydrazinolysis causes a ring-transformation of the oxazoline- to the 1,3,4-triazole systems.
- Martin, D.,Wenzel, A.
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p. 253 - 260
(2007/10/02)
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