- Oxidative Synthesis of Quinazolinones under Metal-free Conditions
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A metal-free procedure for the synthesis of quinazolinones under oxidative conditions has been developed. In the presence of DABCO and TBHP, the desired products can be obtained in moderate yields with 2-fluorobenzaldehydes and 2-aminopyridines as the substrates.
- Feng, Jian-Bo,Wu, Xiao-Feng
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- An Alternative Approach to the Hydrated Imidazoline Ring Expansion (HIRE) of Diarene-Fused [1.4]Oxazepines
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A four-step approach to the “hydrated imidazoline ring expansion” (HIRE) is presented. In most cases, the ring expansion was the sole process. However, for the first time, an alternative course of the hydrated imidazoline evolution was discovered which gave N-aminoethyl derivatives. These can, in principle, be converted into the target HIRE products under sufficiently forcing conditions. The approach offers improved flexibility with respect to the peripheral substituents and is also applicable to the synthesis of eleven-membered lactams. We observed that the latter can exist in two stable isomeric forms due to lactam–amide bond isomerization. The latter finding further demonstrates the value of medium-sized rings as multiple-conformer probes for biological target interrogation.
- Grintsevich, Sergey,Sapegin, Alexander,Reutskaya, Elena,Peintner, Stefan,Erdélyi, Máté,Krasavin, Mikhail
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p. 5664 - 5676
(2020/07/21)
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- One-pot synthesis of substituted dibenzoxazepinones and pyridobenzoxazepinones using octacarbonyldicobalt as an effective CO source
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A facile one-pot protocol for the synthesis of substituted dibenzoxazepinones and pyridobenzoxazepinones from commercially available aryl/heteroaryl halides and amino phenols using octacarbonyldicobalt (Co2(CO)8) as an effective metal carbonyl source has been demonstrated. This method proceeds via the sequential coupling of aryl/heteroaryl halides with aminophenol by amidation and intramolecular cyclization to give dibenzoxazepinones/pyridobenzoxazepinones.
- Anchan, Kavitha,Baburajan, Poongavanam,Puttappa, Nagaswarupa H.,Kumar Sarkar, Sujit
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supporting information
p. 348 - 360
(2019/12/03)
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- Palladium-Catalyzed Carbonylative Synthesis of N-Heterocycles from 1-Chloro-2-fluorobenzenes
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A simple and efficient synthesis of pyrido-fused quinazolinones and dibenzoxazepinones by palladium-catalyzed annulation of commercially available substituted 1-chloro-2-fluorobenzenes and 2-aminopyridines or 2-aminophenols has been developed. The reaction involves carbonylation/aromatic nucleophilic substitution sequential in a one-pot manner.
- Yuan, Yang,Wu, Xiao-Feng
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supporting information
p. 2172 - 2175
(2019/03/17)
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- Design of Conjugated Molecules Presenting Short-Wavelength Luminescence by Utilizing Heavier Atoms of the Same Element Group
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The introduction of heavy atoms into conjugated molecules often induces a redshift in the emission spectra. Conversely, we report here a blueshifting effect in the absorption and emission bands of a conjugated organic dye by employing a heavier atom from the same element group. Boron complexes having oxygen- and sulfur-bridged structures in the ligand moiety were synthesized, and their optical properties were compared. Significant optical bands in the absorption and luminescence spectra of the sulfur-bridged complex were observed in a shorter wavelength region than those of the oxygen-bridged complex. Theoretical calculations suggest that replacement of the bridging atom by a heavier one should reduce molecular planarity because of the larger atom size. As a result, the degree of electronic conjugation decreases, and this is followed by a blueshift in the optical bands. Finally, a blue-emissive crystal is demonstrated.
- Yamaguchi, Madoka,Tanaka, Kazuo,Chujo, Yoshiki
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p. 1342 - 1347
(2018/04/30)
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- Dibenzo[b,f][1,4]oxazepines and dibenzo[b,e]oxepines: Influence of the chlorine substitution pattern on the pharmacology at the H1R, H4R, 5-HT2AR and other selected GPCRs
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Inspired by VUF6884 (7-Chloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine), reported as a dual H1/H4 receptor ligand (pKi: 8.11 (human H1R (hH1R)), 7.55 (human H4R (hH4R))), four known and 28 new oxazepine and related oxepine derivatives were synthesised and pharmacologically characterized at histamine receptors and selected aminergic GPCRs. In contrast to the oxazepine series, within the oxepine series, the new compounds showed high affinity to the hH1R (pKi: 6.8–8.7), but no or moderate affinity to the hH4R (pKi: ≤ 5.3). For one oxepine derivative (1-(2-Chloro-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-4-methylpiperazine), the enantiomers were separated and the R-enantiomer was identified as the eutomer at the hH1R (pKi: 8.83 (R), 7.63 (S)) and the guinea-pig H1R (gpH1R) (pKi: 8.82 (R), 7.41 (S)). Molecular dynamic studies suggest that the tricyclic core of the compounds is bound in a similar mode into the binding pocket, as described for doxepine in the hH1R crystal structure. Moreover, docking studies of all oxepine derivatives at the hH1R indicate that the oxygen and the position of the chlorine in the tricyclic core determines, if the R- or the S-enantiomer is the eutomer. For some of the oxazepines and oxepines the affinity to other aminergic GPCRs is in the same range as to hH1R or hH4R, thus, those compounds have to be classified as dirty drugs. However, one oxazepine derivative (3,7-Dichloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine was identified as dual hH1/h5-HT2A receptor ligand (pKi: 9.23 (hH1R), 8.74 (h5-HT2AR), ≤7 at other analysed GPCRs), whereas one oxepine derivative (1-(3,8-Dichloro-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-4-methylpiperazine) was identified as selective hH1R antagonist (pKi: 8.44 (hH1R), ≤6.7 at other analyzed GPCRs). Thus, the pharmacological results suggest that the oxazepine/oxepine moiety and additionally the chlorine substitution pattern toggles receptor selectivity and specificity.
- Naporra, Franziska,Gobleder, Susanne,Wittmann, Hans-Joachim,Spindler, Julia,Bodensteiner, Michael,Bernhardt, Günther,Hübner, Harald,Gmeiner, Peter,Elz, Sigurd,Strasser, Andrea
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p. 610 - 625
(2016/10/12)
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- Synthesis method of diaryloxazepine ketone compound
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The invention relates to a synthesis method of a diaryloxazepine ketone compound. The synthesis method specifically includes the steps that ortho-hydroxy aryl methyl alcohol, ortho-haloaromaticamine, a ruthenium catalyst, copper salt, a phosphine ligand and alkali are taken and added into an organic solvent, heating is conducted, extraction, drying by distillation and recrystallization are conducted after the reaction is over, and the diaryloxazepine ketone product is obtained. The diaryl and ox-azepine ketone compound is synthesized through one step, the method is easy to operate, economical and efficient, the range of a reaction substrate is wide, the yield is high, and application prospects are wide.
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Paragraph 0014
(2018/02/04)
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- MeOTf- and TBD-Mediated Carbonylation of ortho-Arylanilines with CO2 Leading to Phenanthridinones
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Carbonylation of o-arylanilines utilizing CO2 as a carbonyl source for the synthesis of important phenanthridinones with a free (NH)-lactam motif has been described under metal-free condition. A range of o-arylanilines were transformed to the corresponding phenanthridinones in high yields.
- Wang, Sheng,Shao, Peng,Du, Gaixia,Xi, Chanjuan
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p. 6672 - 6676
(2016/08/16)
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- Tricyclic dihydrobenzoxazepine and tetracyclic indole derivatives can specifically target bacterial DNA ligases and can distinguish them from human DNA ligase I
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DNA ligases are critical components for DNA metabolism in all organisms. NAD+-dependent DNA ligases (LigA) found exclusively in bacteria and certain entomopoxviruses are drawing increasing attention as therapeutic targets as they differ in their cofactor requirement from ATP-dependent eukaryotic homologs. Due to the similarities in the cofactor binding sites of the two classes of DNA ligases, it is necessary to find determinants that can distinguish between them for the exploitation of LigA as an anti-bacterial target. In the present endeavour, we have synthesized and evaluated a series of tricyclic dihydrobenzoxazepine and tetracyclic indole derivatives for their ability to distinguish between bacterial and human DNA ligases. The in vivo inhibition assays that employed LigA deficient E. coli GR501 and S. typhimurium LT2 bacterial strains, rescued by ATP-dependent T4 DNA ligase or Mycobacterium tuberculosis NAD+-dependent DNA ligase (Mtb LigA), respectively, showed that the compounds can specifically inhibit bacterial LigA. The in vitro enzyme inhibition assays using purified MtbLigA, human DNA ligase I & T4 DNA ligase showed specific inhibition of MtbLigA at low micromolar range. Our results demonstrate that tricyclic dihydrobenzoxazepine and tetracyclic indole derivatives can distinguish between bacterial and human DNA ligases by ~5-folds. In silico docking and enzyme inhibition assays identified that the compounds bind to the cofactor binding site and compete with the cofactor. Ethidium bromide displacement and gel-shift assays showed that the inhibitors do not exhibit any unwanted general interactions with the substrate DNA. These results set the stage for the detailed exploration of this compound class for development as antibacterials.
- Yadav, Nisha,Khanam, Taran,Shukla, Ankita,Rai, Niyati,Hajela, Kanchan,Ramachandran, Ravishankar
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p. 5475 - 5487
(2015/05/20)
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- A highly-efficient palladium-catalyzed aminocarbonylation/SNAr approach to dibenzoxazepinones
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A convenient procedure for the synthesis of dibenzoxazepinones has been developed. Utilizing the protocol of one-pot palladium-catalyzed aminocarbonylation/aromatic nucleophilic substitution (SNAr) sequence, with 2-aminophenols and 2-bromofluorobenzenes as the substrates, the desired dibenzo[b,e][1,4]oxazepin-11(5H)-ones were prepared in moderate to excellent yields. The broad substrate scope and functional group tolerance of the reaction makes this approach a practical method for the synthesis of valuable dibenzoxazepinone and its derivatives. Mechanistic studies suggest that aminocarbonylation proceeds prior to SNAr.
- Shen, Chaoren,Neumann, Helfried,Wu, Xiao-Feng
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supporting information
p. 2994 - 2999
(2015/05/27)
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- [bipy.H] hosted by Al-MCM-41: An efficient dibenzo[b,f][1,4]oxazepine (CR) decontamination nano-reactor
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Encapsulation of [Fe(bipy)Cl4][bipy.H] (1) (where bipy is 2,2′-bipyridine) in the Al-MCM-41 molecular sieve by using a "ship in a bottle synthesis" approach was achieved and the product characterized by X-ray diffraction, FTIR, DRS, TG, EDS and BET analysis. Encapsulation of the complex into the channels of Al-MCM-41, did not affect the morphology of the host as is evident from SEM and TEM micrographs. The obtained nanocatalyst in combination with K2S2O8 as the oxidant, was successfully used in selective catalytic conversion of dibenzo[b,f][1,4]oxazepine (CR, riot control agent) to dibenzo[b,f][1,4]oxazepin-11(10H)-one as a potential decontamination route. Good selectivity was also obtained toward formation of benzil in the oxidation of trans-stilbene. This journal is
- Khorshidi, Alireza,Heidari, Sirous
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p. 32804 - 32812
(2015/04/27)
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- Iodine(III)-mediated construction of the dibenzoxazepinone skeleton from 2-(aryloxy)benzamides through oxidative C-N formation
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Dibenzoxazepinone compounds were conveniently synthesized from 2-(aryloxy)benzamides through hypervalent iodine(iii)-mediated oxidative cyclization under mild reaction conditions.
- Guo, Xuliang,Zhang-Negrerie, Daisy,Du, Yunfei
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p. 94732 - 94736
(2015/11/24)
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- Concise palladium-catalyzed synthesis of dibenzodiazepines and structural analogues
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A general and highly efficient protocol for the synthesis of dibenzodiazepines and their structural analogues is reported. In the presence of catalytic quantities of palladium, readily accessible precursors are cross-coupled with ammonia and then spontaneously undergo an intramolecular condensation to form the corresponding dibenzodiazepines in one step. This new strategy is applicable to the construction of a wide variety of dibenzooxazepines and other structurally related heterocycles.
- Tsvelikhovsky, Dmitry,Buchwald, Stephen L.
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supporting information; experimental part
p. 14228 - 14231
(2011/10/31)
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- Synthesis of dibenzo[ b, f ][1,4]oxazepin-11(10 H)-ones via intramolecular cyclocarbonylation reactions using PdI2/Cytop 292 as the catalytic system
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Figure presented. The intramolecular cyclocarbonylation of substituted 2-(2-iodophenoxy)anilines was catalyzed by PdI2 and 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phospha-adamantane (Cytop 292) in an efficient manner. A series of substituted dibenzo[b,f][1,4]oxazepin-11(10H)- ones were prepared in good yields under mild reaction conditions.
- Yang, Qian,Cao, Hong,Robertson, Al,Alper, Howard
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supporting information; experimental part
p. 6297 - 6299
(2010/11/17)
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- N-Hydroxyamides Omege-Substituted with Tricyclic Groups as Histone Deacetylase Inhibitors, Their Preparation and Use in Pharmaceutical Formulations
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New N-hydroxyamides of n-alkyl carboxylic acids omega substituted with suitable tricyclic systems characterised by a central 7-membered ring, having activity as inhibitors of histone deacetylase (HDAC).
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Page/Page column 6
(2008/12/08)
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- Synthesis and evaluation of antipsychotic activity of 11-(4-aryl-1- piperazinyl)-dibenz [b, f][1,4] oxazepines and their 8-chloro analogues
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Atypical drugs reduce positive and negative symptoms of schizophrenia, without inducing EPS, but they exert other undesirable side effects. We have gone for synthesis of novel derivatives of Loxapine which are devoid of catalepsy and have decreased metabolic demethylation which is the prominent factor for bioavailability of the drug. While doing so we have also been successful in retaining the antipsychotic activity of the drug. Condensation of 8,11-dichlorodibenzoxazepine and 11-chlorodibenzoxazepine with 1-aryl piperazines was carried to give 8-chloro-11-(4-aryl-1-piperazinyl)-dibenz[b,f] [1,4]oxazepines and 11-(4-aryl-1-piperazinyl)-dibenz[b,f][1,4]oxazepines respectively. These derivatives were found as active as Clozapine.
- Wagh,Patil,Jain,Harak,Wagh
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p. 165 - 172
(2008/02/12)
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- N-HYDROXYAMIDES OMEGA-SUBSTITUTED WITH TRICYCLIC GROUPS AS HISTONE DEACETYLASE INHIBITORS, THEIR PREPARATION AND USE IN PHARMACEUTICAL FORMULATIONS
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New N-hydroxyamides of n-alkyl carboxylic acids omega substituted with suitable tricyclic systems characterised by a central 7-membered ring, having activity as inhibitors of histone deacetylase (HDAC).
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Page/Page column 16
(2010/11/23)
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- Dibenzo-fused seven-membered nitrogen heterocycles by a tandem reduction-lactamization reaction
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Efficient syntheses of dibenz[b,f][1,4]oxazepin-11(10H)-one, 5,10-dihydro-11H-dibenzo[b,e][1,4]-diazepin-11-one and 5,11-dihydro-6H-dibenz[b, e]azepin-6-one are described using a tandem reduction-lactamization sequence. Precursors for these ring systems are available in 1-3 steps using nucleophilic aromatic substitution and Ullmann coupling methodology. Direct reduction-lactamization of these compounds using iron powder in acetic acid at 115° affords the target heterocycles in ≥90% yield.
- Bunce, Richard A.,Schammerhorn, James E.
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p. 1031 - 1035
(2007/10/03)
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- Synthesis of dibenzo[b,f][1,4]oxazepin-11(10H)-ones from 2-nitrobenzoic acids
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Base-catalyzed intramolecular nucleophilic substitution for the 2-nitro group in 2-hydroxyanilides of 2-nitrobenzoic acids gave dibenzo[b,f][1,4] oxazepin-11(10H)-ones. In particular, 3-nitrodibenzo[b, f][1,4]oxazepin-11(10H)- one was obtained from N-(2-hydroxyphenyl)-2,4-dinitrobenzamide. The nitro group in the product could also be replaced under the action of O- and S-nucleophiles.
- Samet,Kislyi,Marshalkin,Semenov
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p. 549 - 553
(2007/10/03)
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- Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives
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A series of dibenzodiazepine derivatives was synthesized to probe the binding site of the recently discovered histamine H4 receptor (H 4R). Optimization of the lead structure clozapine (2) resulted in (E)-7-chloro-11(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine (7j), a potent H4R agonist (H4R, pK, = 7.6). Pharmacological data suggests that the series of nonimidazole compounds can be used to describe the orthosteric binding site of the H4R because both 2 and 7j displace [3H]histamine in a competitive manner. Furthermore, it is demonstrated that the effects of 7j are competitively antagonized by the selective H4R antagonist JNJ 7777120 (1), indicating considerable overlap of their binding sites. On the basis of the derived structure-activity relationships and additional pharmacological results, a pharmacophore model was constructed, which will be the premise for the design of novel H4R ligands.
- Smits, Rogier A.,Lim, Herman D.,Stegink, Bart,Bakker, Remko A.,De Esch, Iwan J. P.,Leurs, Rob
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p. 4512 - 4516
(2007/10/03)
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- Loxapine analogs and methods of use thereof
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The invention relates to novel compounds and methods of using them for modulating sleep.
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Page/Page column 75-76
(2008/06/13)
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- Intramolecular carbonylation reactions with recyclable palladium-complexed dendrimers on silica: Synthesis of oxygen, nitrogen, or sulfur-containing medium ring fused heterocycles
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Palladium-complexed dendrimers supported on silica were evaluated as catalysts for intramolecular carbonylation reactions. The results showed that dendritic catalysts display high activity, affording oxygen, nitrogen, or sulfur-containing seven- or eight-membered ring fused heterocycles in excellent yields. Moreover, these catalysts have competitive advantages in that they can be easily recovered by simple filtration in air and reused for up to eight cycles with only a slight loss of activity.
- Lu, Shui-Ming,Alper, Howard
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p. 14776 - 14784
(2007/10/03)
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- Desulfonylation of amides using tributyltin hydride, samarium diiodide or zinc/titanium tetrachloride. A comparison of methods
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Deprotection of N-sulfonylated amides can be achieved by reaction with Bu3SnH, SmI2 or TiCl4/Zn. All three methods gave good yields (typically >60%) when using N-benzoyl or related amides while the corresponding N~acetyl derivatives proved to be inert to deprotection under the same reaction conditions. The mechanistic implications of this are discussed. (C) 2000 Elsevier Science Ltd.
- Knowles, Haydn S.,Parsons, Andrew F.,Pettifer, Robert M.,Rickling, Stéphane
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p. 979 - 988
(2007/10/03)
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- A radical approach to debenzylation of amides
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The deprotection of N-benzylamides can be achieved under neutral conditions by reaction with N-bromosuccinimide in boiling chlorobenzene or ethyl acetate. Good to excellent yields are obtained using either acyclic or cyclic amides.
- Baker, S. Richard,Parsons, Andrew F.,Wilson, Michelle
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p. 331 - 332
(2007/10/03)
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- Desulfonylation of Amides Using Samarium Iodide
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The desulfonylation of N-sulfonyl amides can be achieved in reasonable to excellent yield by reaction with samarium(II) iodide (SmI2) in THF at room temperature. Deprotection of acyclic and cyclic amides bearing aryl and alkylsulfonyl groups is possible.
- Knowles, Haydn,Parsons, Andrew F.,Pettifer, Robert M.
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p. 271 - 272
(2007/10/03)
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- A radical approach to N-desulfonylation
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The deprotection of N-sulfonylated amides can be achieved under neutral conditions by reaction with tributyltin hydride. Good yields are obtained using N-benzoyl and related amides while the corresponding N-acetyl derivatives are inert under the same reaction conditions. The mechanistic implications of this are discussed.
- Parsons, Andrew F.,Pettifer, Robert M.
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p. 1667 - 1670
(2007/10/03)
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- A highly selective protocol for the deprotection of BOC-protected amides and carbamates
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A BOC-protected amide or carbamate undergoes mild and selective deprotection by treatment with catalytic Mg(ClO4)2 in acetonitrile. Simple BOC-protected amines are not affected by these conditions.
- Stafford, Jeffrey A.,Brackeen, Marcus F.,Karanewsky, Donald S.,Valvano, Nicole L.
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p. 7873 - 7876
(2007/10/02)
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- Novel Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase. 2. Tricyclic Pyridobenzoxazepinones and Dibenzoxazepinones
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Dibenzoxazepin-11(10H)-ones (III), pyridobenzoxazepin-6(5H)-ones (IV), and pyridobenzoxazepin-5(6H)-ones (V) were found to inhibit human immunodeficiency virus type 1 reverse transcriptase with IC50 values as 19 nM.A-ring substitution has a profound effect on activity, with appropriate substituents at the positions ortho and para to the lactam nitrogen providing dramatically enhanced potency.Substitution in the C-ring is generally neutral or detrimental to activity.Although a C-ring amino substituent at the position meta to the lactam carbonyl is generally beneficial to activity, it has essentially no effect when the A-ring is optimally substituted.Like the dipyridodiazepinone nevirapine, compounds III-V are specific for HIV-1 RT, exhibiting no inhibitory activity against HIV-2 RT or other virial reverse transcriptase enzymes.
- Klunder, Janice M.,Hargrave, Karl D.,West, MaryAnn,Cullen, Ernest,Pal, Kollol,et al.
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p. 1887 - 1897
(2007/10/02)
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- Synthesis of 11-Oxo and 11,11-Diphenyl Derivatives of Dibenzothiazepines, Dibenzooxazepines and Dibenzodiazepines
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11-Oxo (IIa-c) and 11,11-diphenyl (IVa-c) derivatives of dibenzothiazepine, dibenzooxazepine and dibenzodiazepine have been prepared by treating the lithiated intermediates with carbon dioxide and benzophenone respectively.
- Shete, N. R.
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p. 581 - 582
(2007/10/02)
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