- Self-Immolative System for Disclosure of Reactive Electrophilic Alkylating Agents: Understanding the Role of the Reporter Group
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The development of stable, efficient chemoselective self-immolative systems, for use in applications such as sensors, requires the optimization of the reactivity and degradation characteristics of the self-immolative unit. In this paper, we describe the effect that the structure of the reporter group has upon the self-immolative efficacy of a prototype system designed for the disclosure of electrophilic alkylating agents. The amine of the reporter group (a nitroaniline unit) was a constituent part of a carbamate that functioned as the self-immolative unit. The number and position of substituents on the nitroaniline unit were found to play a key role in the rate of self-immolative degradation and release of the reporter group. The position of the nitro substituent (meta- vs para-) and the methyl groups in the ortho-position relative to the carbamate exhibited an influence on the rate of elimination and stability of the self-immolative system. The ortho-methyl substituents imparted a twist on the N-C (aromatic) bond leading to increased resonance of the amine nitrogen's lone pair into the carbonyl moiety and a decrease of the leaving character of the carbamate group; concomitantly, this may also make it a less electron-withdrawing group and lead to less acidification of the eliminated β-hydrogen.
- Chippindale, Ann M.,Gavriel, Alexander G.,Hayes, Wayne,Khurana, Gurjeet S.,Leroux, Flavien,Lewis, Viliyana G.,Russell, Andrew T.,Sambrook, Mark R.
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p. 10263 - 10279
(2021/08/16)
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- Pd-Catalyzed Ortho-Directed C—H Glycosylation of Arenes Using N-linked Bidentate Auxiliaries
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A set of Pd-catalyzed ortho-directed C—H glycosylation reactions with glycosyl chloride donors using various N-linked bidentate auxiliaries has been developed for synthesis of C-aryl glycosides. A broad range of pyranose and furanose moieties can be installed on the ortho position of arylamine, carbazole, indole and benzylamine type substrates in high yield and with high regio- and diastereoselectivity. These auxiliaries can be readily installed and removed under relatively mild conditions.
- Wang, Quanquan,Zhu, Wanjun,Sun, Qikai,He, Gang,Chen, Gong
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supporting information
p. 571 - 576
(2021/02/01)
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- Ir-Catalyzed C-H Amidation Using Carbamoyl Azides for the Syntheses of Unsymmetrical Ureas
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An iridium-catalyzed C-H amidation for the syntheses of unsymmetrical urea was developed using carbamoyl azides (R(R′)N-C(O)-N3) as the nitrogen source. A combination of iridium and silver gave an active catalyst for C-N bond formation. A variety of urea derivatives were synthesized using carbamoyl azides with only dinitrogen byproducts. Finally, the use of the transient directing group strategy with carbamoyl azides extended the substrate scope of the catalytic C-H amidation to yield aldehyde-containing unsymmetrical ureas.
- Yoo, Kwangho,Lee, Jooyeon,Park, Myung Hwan,Kim, Youngjo,Kim, Hyun Jin,Kim, Min
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p. 6233 - 6241
(2020/05/22)
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- Nickel/Photo-Cocatalyzed Asymmetric Acyl-Carbamoylation of Alkenes
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An unprecedented asymmetric acyl-carbamoylation of pendant alkenes tethered on aryl carbamic chlorides with both aliphatic and aromatic aldehydes has been developed via the cooperative catalysis of a chiral nickel-PHOX complex and tetrabutylammonium decatungstate. This reaction represents the first example of merging hydrogen-atom-transfer photochemistry and asymmetric transition metal catalysis in difunctionalization of alkenes. Using this protocol, a variety of oxindoles bearing a challenging quaternary stereogenic center are furnished under mild conditions in highly enantioselective manner.
- Fan, Pei,Lan, Yun,Zhang, Chang,Wang, Chuan
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supporting information
p. 2180 - 2186
(2020/03/03)
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- Method for continuously synthesizing buprofezin
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The invention discloses a method for continuously synthesizing buprofezin, and belongs to the technical field of chemical synthesis. The method for continuously synthesizing buprofezin comprises the following steps: S1, continuously acylating N-methylaniline and phosgene in a solvent, and continuously deacidifying to obtain an acyl chloride solution; S2, carrying out continuous chlorination and continuous deacidification on the acyl chloride solution and chlorine under the action of an initiator to obtain a chloride solution; S3, adding buprothiourea, a catalyst and an acid-binding agent intothe chloride solution, carrying out continuous mixing reaction, crystallizing and drying a reaction product to obtain buprofezin of which the content is greater than or equal to 99.0% and the total yield is greater than or equal to 88% based on N-methylaniline. The method for continuously synthesizing buprofezin solves the defects caused by batch production in China, has the advantages of continuous reaction, high automation degree, small equipment size, high operation safety, few side reaction products, high conversion rate and good product quality, can effectively improve the production efficiency and reduce the production cost, and has very good popularization and application values.
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Paragraph 0043-0061
(2020/12/30)
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- Chemoenzymatic Synthesis of Substituted Azepanes by Sequential Biocatalytic Reduction and Organolithium-Mediated Rearrangement
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Enantioenriched 2-aryl azepanes and 2-arylbenzazepines were generated biocatalytically by asymmetric reductive amination using imine reductases or by deracemization using monoamine oxidases. The amines were converted to the corresponding N′-aryl ureas, which rearranged on treatment with base with stereospecific transfer of the aryl substituent to the 2-position of the heterocycle via a configurationally stable benzyllithium intermediate. The products are previously inaccessible enantioenriched 2,2-disubstituted azepanes and benzazepines.
- Zawodny, Wojciech,Montgomery, Sarah L.,Marshall, James R.,Finnigan, James D.,Turner, Nicholas J.,Clayden, Jonathan
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supporting information
p. 17872 - 17877
(2019/01/04)
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- Rhodium catalyzed regioselective arene homologation of aryl urea via double C–H bond activation and migratory insertion of alkyne
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A convenient rhodium catalyzed oxidative arene homologation of aniline derivatives with symmetrical or unsymmetrical alkynes using Cu(OAc)2as oxidant is described. Urea group is shown to be effective as a directing group for initial ortho C–H activation. Two migratory insertion events of alkyne into Rh–C bond occur successively, both with complete regioselectivity. This method is particularly useful for synthesis of polyarenes with different substituents, which has not been reported with conventional protocol. A mechanism has been proposed to explain the observed data.
- Wang, Yan,Zhou, Hao,Xu, Ke,Shen, Mei-Hua,Xu, Hua-Dong
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- Synthesis of 3- and 29-substituted celastrol derivatives and structure-activity relationship studies of their cytotoxic activities
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A series of 3-carbamate and 29-ester celastrol derivatives (compounds 1–26) were designed and synthesized. These analogues were evaluated for their cytotoxic activities against several cancer cell lines. Cytotoxicity data revealed that the properties of substituents and substitution position had important influence on cytotoxic activity. Modification of C-3 hydroxyl with size-limited groups did not reduce the activity obviously. The introduction of polarity group like piperazine could improve the solubility. Compound 23 was chosen to further evaluate anti-tumor efficacy in vivo. It showed higher inhibition rate and better safety than celastrol during in vivo experiment by intragastric administration. The preliminary antitumor studies of compound 23 in vivo showed that it might be promising for the development of new antitumor agents.
- Shan, Wei-Guang,Wang, Han-Guang,Chen, Yan,Wu, Rui,Wen, Yan-Tao,Zhang, Li-Wen,Ying, You-Min,Wang, Jian-Wei,Zhan, Zha-Jun
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supporting information
p. 3450 - 3453
(2017/07/07)
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- Buprofenzin process for the preparation of
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The invention relates to a preparation method of buprofezin, which comprises the following steps of actinism, chlorination, synthesis and distillation crystallization. The actinism step employs dioxane or chloroform, the chlorination step employs dioxane or N-chloromethyl-N-phenyl carbamyl chloride as a solvent; and the synthesis step employs organic amine to participate in condensation. According to the invention, dioxane, chloroform or N-chloromethyl-N-phenyl carbamyl chloride are employed as the solvents, so that good dissolving performance is provided to the raw material, and the dioxane, chloroform or N-chloromethyl-N-phenyl carbamyl chloride has little solubility to HCL and is in favor of reaction, the production yield can reach as high as more than 82%; organic amine is employed for replacing ammonium bicarbonate as alkali for synthesis reaction, and can be recovered so that the discharge of ammonia nitrogen in waste water is reduced.
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Paragraph 0010-0011; 0015-0016; 0020-0021; 0025-0026; 0030
(2019/11/28)
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- Optimization of 1,2,5-thiadiazole carbamates as potent and selective ABHD6 inhibitors
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At present, inhibitors of α/β-hydrolase domain 6 (ABHD6) are viewed as a promising approach to treat inflammation and metabolic disorders. This article describes the development of 1,2,5-thiadiazole carbamates as ABHD6 inhibitors. Altogether, 34 compounds were synthesized, and their inhibitory activity was tested using lysates of HEK293 cells transiently expressing human ABHD6 (hABHD6). Among the compound series, 4-morpholino-1,2,5-thiadiazol-3-yl cyclooctyl(methyl)carbamate (JZP-430) potently and irreversibly inhibited hABHD6 (IC50 = 44 nM) and showed ~ 230-fold selectivity over fatty acid amide hydrolase (FAAH) and lysosomal acid lipase (LAL), the main off-targets of related compounds. Additionally, activity-based protein profiling indicated that JZP-430 displays good selectivity among the serine hydrolases of the mouse brain membrane proteome. JZP-430 has been identified as a highly selective, irreversible inhibitor of hABHD6, which may provide a novel approach in the treatment of obesity and type II diabetes.
- Patel, Jayendra Z.,Nevalainen, Tapio J.,Savinainen, Juha R.,Adams, Yahaya,Laitinen, Tuomo,Runyon, Robert S.,Vaara, Miia,Ahenkorah, Stephen,Kaczor, Agnieszka A.,Navia-Paldanius, Dina,Gynther, Mikko,Aaltonen, Niina,Joharapurkar, Amit A.,Jain, Mukul R.,Haka, Abigail S.,Maxfield, Frederick R.,Laitinen, Jarmo T.,Parkkari, Teija
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p. 253 - 265
(2015/02/05)
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- A novel and efficient strategy for the synthesis of various carbamates using carbamoyl chlorides under solvent-free and grinding conditions using microwave irradiation
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We present an efficient, fast and simple strategy of generating the intermediate carbamoyl chlorides from secondary amines using stoichiometric amounts of bis(trichloromethyl)carbonate (BTC) in solution and solvent-free conditions with excellent yields. The results obtained showed the yield increasing on whether a base was used. Finally, an efficient and rapid synthesis of variety carbamate derivatives was developed by the reaction with a high variety of different alcohols, phenols, diols and this intermediate at room temperature with grinding and in solvent-free conditions under microwave irradiation. The presence of various safe bases is shown to be effective in reducing the reaction times, increasing the yields and easing purification. The present method does not involve any hazardous phosgene.
- Zare, Hassan,Ghanbari, Mohammad Mehdi,Jamali, Marzieh,Aboodi, Abdollah
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scheme or table
p. 883 - 886
(2012/08/28)
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- Unexpected zirconium-mediated multicomponent reactions of conjugated 1,3-butadiynes and monoynes with acyl cyanide derivatives
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Going ber(zirc): Zirconium-butadiyne complexes react with acyl cyanide derivatives through diverse reaction pathways. The complexes react with two molecules of carbamoyl cyanide to form 1,4-benzodiazepin-2-one-derivatives containing azazirconacycles. Reac
- Yu, Shasha,You, Xu,Liu, Yuanhong
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supporting information
p. 13936 - 13940
(2013/01/15)
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- Synthetic routes to, transformations of, and rather surprising stabilities of (N-Methyl-N-phenylcarbamoyl)sulfenyl Chloride, ((N-Methyl-N-phenylcarbamoyl) dithio)carbonyl chloride, and related compounds
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(Figure presented) The title compound classes, (carbamoyl)sulfenyl chlorides and ((carbamoyl)dithio)carbonyl chlorides, have been implicated previously as unstable, albeit trappable, intermediates in organosulfur chemistry. The presentwork reports for each of these functional groups: (i) several routes to prepare it in the N-methylaniline family; (ii) its direct structural characterization by several spectroscopic techniques; (iii) its rather unexpected stability and its ultimate fatewhen it decomposes; (iv) a series of further chemical transformations that give highly stable derivatives, each in turn subject to thorough characterization. Relevant kinetic and mechanistic experiments were carried out, including some with p-methyl- and 2,6-dimethyl-substituted N-methylanilines. Given that the title compounds can be isolated and are relatively stable, they may find applications in the preparation of thiolyzable and/or photolabile protecting groups for the sulfhydryl function of cysteine and for the development of new protein synthesis and modification reagents
- Schrader, Alex M.,Schroll, Alayne L.,Barany, George
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p. 7882 - 7892
(2011/12/14)
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- Iridium-catalyzed annulation of N -arylcarbamoyl chlorides with internal alkynes
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An iridium complex successfully catalyzed the annulation of various N-arylcarbamoyl chlorides with internal alkynes to afford 2-quinolones in good to excellent yields. The present reaction is widely applicable to substrates with various functionalities. An amide-iridacycle complex was isolated, and it is likely that such an iridacycle species is a key intermediate in the catalytic reaction.
- Iwai, Tomohiro,Fujihara, Tetsuaki,Terao, Jun,Tsuji, Yasushi
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supporting information; experimental part
p. 9602 - 9603
(2010/08/22)
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- 1-Amido-1-phenyl-3-piperidinylbutanes - CCR5 antagonists for the treatment of HIV. Part 1
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The development of a new class of CCR5 antagonist replacing the tropane core of maraviroc by piperidine with a branched N-substituent is described. Compound 15h shows good whole cell antiviral activity together with microsomal stability and only weak activity at the hERG ion channel.
- Barber, Christopher G.,Blakemore, David C.,Chiva, Jean-Yves,Eastwood, Rachel L.,Middleton, Donald S.,Paradowski, Kerry A.
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scheme or table
p. 1075 - 1079
(2009/08/07)
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- One-pot radiosynthesis of [13N]urea and [13N] carbamate using no-carrier-added [13N]NH3
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The aim of this study was to develop a practical labeling method of [ 13N]ligands using no-carrier-added [13N]NH3 with high specific activity. [13N]urea analogues [13N]1a and [13N]2a or [13N]carbamate [13N]3a were synthesized by reacting isocyanate 5a, carbamoyl chloride 6a or chloroformate 7a with [13N]NH3. The precursors 5a-7a were prepared by treating amines 8a and 9a and alcohol 10a with triphosgene in situ. These reaction mixtures were not purified and were used directly for [ 13N]ammonolysis, respectively. Using the one-pot method, we synthesized [13N]carbamazepine ([13N]4), a putative positron emission tomography ligand for brain imaging. Copyright
- Kumata, Katsushi,Takei, Makoto,Ogawa, Masanao,Kato, Koichi,Suzuki, Kazutoshi,Zhang, Ming-Rong
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experimental part
p. 166 - 172
(2010/07/02)
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- Electronic interactions in tertiary oligophenylureas
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The syntheses, structures, and spectroscopy of a series of oligomeric tertiary oligophenylureas possessing one to five phenyl rings are reported. A convergent synthetic method employing tertiary monoamine and diamine building blocks is employed. NMR and molecular modeling are indicative of folded structures for all of the oligophenylureas in which adjacent phenyl rings have a splayed face-to-face geometry. NMR chemical shifts, absorption and emission maxima, and electrochemical oxidation potentials are all dependent upon the number of phenyl rings. The addition of a first inner phenyl has a pronounced effect on the chemical shifts, while a second and third inner phenyl have diminished effects. The oxidation potentials of the oligophenylureas display an abrupt decrease upon the addition of the second inner phenyl. The absorption and emission spectra are relatively insensitive to the addition of one to three inner phenyl rings. The electronic structures of the oligophenylureas possessing one to eight rings have been analyzed using ZINDO calculations. The frontier orbitals of the ureas with one to three phenyl rings are localized on a single phenyl ring (the inner ring for the three-ring urea), whereas the frontier orbitals of the higher oligomers are delocalized over two phenyl rings. In all cases, urea-localized n,π* transitions are lower in energy than the phenyl-localized n,π* transitions. The changes in properties with added phenyl rings parallel those previously observed for multilayered cyclophanes; however, they are less pronounced because of weaker coupling between the phenyl rings of the oligophenylureas.
- Lewis, Frederick D.,Kurth, Todd L.,Delos Santos, Grace B.
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p. 4893 - 4899
(2008/03/14)
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- Radical Chain Reaction or Benzenethiol with Pentynylthiol Esters: Production of Aldehydes under Stannane/Silane-Free Conditions
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The radical chain reaction of benzenethiol with accessible 4-pentynylthiol esters provides a new stannane/silane-free protocol for the production of aromatic and aliphatic aldehydes. The procedure is especially useful for the aryl and primary aldehydes, even in the presence of substituents highly sensitive to reductive conditions, and is also of some utility for the vinylic and secondary ones, The protocol is instead not applicable to the tertiary aldehydes, owing to preferential alkane-forming decarbonylation, although the tertiary ones derived from bridgehead precursors can still be usefully produced.
- Benati, Luisa,Leardini, Rino,Minozzi, Matteo,Nanni, Daniele,Scialpi, Rosanna,Spagnolo, Piero,Zanardi, Giuseppe
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p. 985 - 990
(2007/10/03)
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- Debenzylation of tertiary amines using phosgene or triphosgene: An efficient and rapid procedure for the preparation of carbamoyl chlorides and unsymmetrical ureas. Application in carbon-11 chemistry
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Efficient and rapid preparations of carbamoyl chlorides and unsymmetrical ureas from tertiary amines and phosgene or its safe equivalent triphosgene [bis(trichloromethyl)carbonate, BTC] are described. First, the reaction of stoichiometric amounts of phosgene with secondary amines was revisited, and it was shown that the formation of carbamoyl chlorides in high yields required careful adjustments of experimental conditions and the use of pyridine as an HCl scavenger. A phosgene-mediated dealkylation of triethylamine was observed when this base was used instead of pyridine. Taking advantage of this observation, a strategy of synthesis of carbamoyl chlorides from tertiary amines and phosgene has been developed. N-Alkyl-N-benzyl(substituted)tetrahydroisoquinolines, -piperazines, -piperidines, or -anilines were treated with stoichiometric amounts of phosgene (or BTC) in CH2Cl2. Tertiary amines bearing electron-enriched benzyl group(s) afforded carbamoyl chlorides in excellent yields and without any contamination by symmetrical ureas. Subsequent additions of primary or secondary amines to these carbamoyl chlorides produced unsymmetrical ureas in single-pot and high-yielding operations. This methodology was applied in 11C-chemistry. From [ 11C]phosgene, a common precursor used in the preparation of radiotracers for positron emission tomography, a rapid and efficient synthesis of 11C-carbamoyl chlorides and 11C-unsymmetrical ureas derived from tetrahydroisoquinoline and piperazine is described. The first example of 11C-amide formation from the reaction of a 11C-carbamoyl chloride and an organometallic (cyanocuprate or a Grignard reagent in the presence of a nickel catalyst) is also presented.
- Lemoucheux, Laurent,Rouden, Jacques,Ibazizene, Me?ziane,Sobrio, Franck,Lasne, Marie-Claire
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p. 7289 - 7297
(2007/10/03)
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- New class of biphenylene dibenzazocinones as potent ligands for the human EP1 prostanoid receptor
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A new class of potent and selective ligands for the human EP1 prostanoid receptor is described. SAR studies reported herein allowed the identification of several potent dibenzazocinones bearing an acylsulfonamide side chain. The binding affinity of these compounds on all eight human prostanoid receptors is reported.
- Ruel, Rejean,Lacombe, Patrick,Abramovitz, Mark,Godbout, Claude,Lamontagne, Sonia,Rochette, Chantal,Sawyer, Nicole,Stocco, Rino,Tremblay, Nathalie M.,Metters, Kathleen M.,Labelle, Marc
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p. 2699 - 2704
(2007/10/03)
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- Process for the preparation of 1-4-disubstituted-5 (4H)-tetrazolinones
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1,4-Disubstituted-5(4H)-tetrazolinones of the formula (I) STR1 wherein R1, R2 and R3 have the meanings given in the specification), which are known to be useful as herbicides, can be obtained in very good yields by reacting the corresponding 1-substituted-5(4H)-tetrazolinones with the corresponding carbamoyl chlorides in the presence of 4-dimethylaminopyridine.
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- Mesolimbic selective antipsychotic arylcarbamates
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4-(6-Fluoro-1,2-benzisoxazol-3-yl)piperidine has been linked to various arylcarbamates to obtain compounds having affinity for dopamine-D1 and -D2, serotonin 5HT(2A) and α1-adrenoceptors. When linkers with restricted flexibility are used, the biological activity is reduced indicating that a bended conformation is needed in this series of bioactive molecules. Compounds with a relatively low D2/5HT(2A) affinity ratio in receptor binding experiments and high affinity for the α1-adrenoceptors exhibit a pharmacological profile which suggests a preferential effect on the mesocorticolimbic dopaminergic system and an 'atypical' antipsychotic activity.
- Hansen, John Bondo,Fink-Jensen, Anders,Christensen, Birgitte V.,Gronvald, Frederick C.,Jeppesen, Lone,Mogensen, John P.,Nielsen, Erik B.,Scheideler, Mark A.,White, Francis J.,Zhang, Xu-Feng
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p. 839 - 858
(2007/10/03)
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- Synthesis of symmetrical and unsymmetrical ureas using unsymmetrical diaryl carbonates
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Appropriately substituted unsymmetrical diaryl carbonates react smoothly with primary amines to give the carbamates derived by nucleophilic displacement of the less electron rich aromatic substituent. Subsequent treatment of the carbamates with primary and secondary amines gives either symmetrical or unsymmetrical ureas in excellent yield and the overall process can be carried out as a 'one pot' operation. Acetonitrile is the preferred solvent and addition of DBU facilitates the carbamate → urea transformation.
- Freer, Richard,McKillop, Alexander
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p. 331 - 349
(2007/10/03)
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- CORRELATION BETWEEN THE STRUCTURE AND ACTIVITY OF AMINOSTIGMINE DERIVATIVES CONTAINING VARIOUS SUBSTITUENTS AT THE NITROGEN ATOM OF THE CARBAMOYL GROUP
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Sixteen aminostigmine derivatives containing various substituents at the nitrogen atom of the carbamoyl group have been prepared, and their anticholine esterase activity in vitro, ionization constants, hydrophobicity, and toxicity have been determined.
- Prozorovskii, V. B.,Pavlova, L. V.,Suslova, I. M.,Belozerova, L. V.,Kokushkina, A. V.,Sazonova, A. V.
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p. 589 - 593
(2007/10/03)
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- 4-[diaryl)hydroxymethyl]-1-piperidinealkylcarboxylic acids, salts and esters useful in the treatment of allergic disorders
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Novel compounds useful in the treatment of allergic disorders and having the formula: STR1 where Ar and Ar1 are pyridinyl, phenyl, or substituted phenyl and where Y is --OH,--O? M≈ m,--O--loweralkyl, --O--Aryl, or NR1 R2 (R1, R2 =H, loweralkyl, aryl) are herein disclosed.
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- Pesticidal cyclic malonylphosphonic diamides
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Novel pesticidally active cyclic malonylphosphonic diamides of the formula STR1 in which X represents O or S, R1 represents alkyl, alkenyl, alkinyl, cycloalkyl, aryl or heteroaryl, each of which can be optionally substituted, R2 represents hydrogen, alkyl, aryl or aralkyl, R3 represents hydrogen, alkyl, aryl or aralkyl, and R4 represents an acyl radical, or salts thereof, Many intermediates are new,
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- Anthelmintic 1-(substituted phenyl)-3-alkanimidoyl ureas
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The compounds of this invention are novel imidoylureas having anthelmintic activity and imidoylthioureas having antifertility activity. They are prepared by the reaction of appropriate amidines with appropriate isocyanates or isothiocyanates.
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