- Lewis acid catalyzed nitrile synthesis from aldehyde
-
In DMA solvent, the one-pot conversion of aldehydes to their corresponding nitriles was studied in Lewis acid catalyst's system (Ca(OTf)2/Bu4NPF6) and hydroxylamine hydrochloride at 120 °C. The developed synthesis method w
- Bariya, Dipakkumar,Mishra, Satyendra
-
supporting information
(2022/03/16)
-
- N-skatyltryptamines-dual 5-ht6r/d2r ligands with antipsychotic and procognitive potential
-
A series of N-skatyltryptamines was synthesized and their affinities for serotonin and dopamine receptors were determined. Compounds exhibited activity toward 5-HT1A, 5-HT2A, 5-HT6, and D2 receptors. Substitution patterns resulting in affinity/activity switches were identified and studied using homology modeling. Chosen hits were screened to determine their metabolism, permeability, hepatotoxicity, and CYP inhibition. Several D2 receptor antagonists with additional 5-HT6R antagonist and agonist properties were identified. The former combination resembled known antipsychotic agents, while the latter was particularly interesting due to the fact that it has not been studied before. Selective 5-HT6R antagonists have been shown previously to produce procognitive and promnesic effects in several rodent models. Administration of 5-HT6R agonists was more ambiguous-in naive animals, it did not alter memory or produce slight amnesic effects, while in rodent models of memory impairment, they ameliorated the condition just like antagonists. Using the identified hit compounds 15 and 18, we tried to sort out the difference between ligands exhibiting the D2R antagonist function combined with 5-HT6R agonism, and mixed D2/5-HT6R antagonists in murine models of psychosis.
- Bojarski, Andrzej J.,Bugno, Ryszard,Cie?lik, Paulina,Duszyńska, Beata,Handzlik, Jadwiga,Hogendorf, Adam S.,Hogendorf, Agata,Kaczorowska, Katarzyna,Kurczab, Rafa?,Latacz, Gniewomir,Lenda, Tomasz,Sata?a, Grzegorz,Staroń, Jakub,Szewczyk, Bernadeta
-
-
- Fe-catalyzed Fukuyama-type indole synthesis triggered by hydrogen atom transfer
-
Fe, Co, and Mn hydride-initiated radical olefin additions have enjoyed great success in modern synthesis, yet the extension of other hydrogen radicalophiles instead of olefins remains largely elusive. Herein, we report an efficient Fe-catalyzed intramolec
- Huang, Hanmin,Yu, Min,Zhang, Tianze
-
p. 10501 - 10505
(2021/08/20)
-
- Iron-Catalyzed α-C-H Cyanation of Simple and Complex Tertiary Amines
-
This manuscript details the development of a general and mild protocol for the α-C-H cyanation of tertiary amines and its application in late-stage functionalization. Suitable substrates include tertiary aliphatic, benzylic, and aniline-type substrates and complex substrates. Functional groups tolerated under the reaction conditions include various heterocycles and ketones, amides, olefins, and alkynes. This broad substrate scope is remarkable, as comparable reaction protocols for α-C-H cyanation frequently occur via free radical mechanisms and are thus fundamentally limited in their functional group tolerance. In contrast, the presented catalyst system tolerates functional groups that typically react with free radicals, suggesting an alternative reaction pathway. All components of the described catalyst system are readily available, allowing implementation of the presented methodology without the need for lengthy catalyst synthesis.
- Yilmaz, Ozgur,Dengiz, Cagatay,Emmert, Marion H.
-
supporting information
p. 2489 - 2498
(2021/02/06)
-
- Asymmetric Dearomatizing Fluoroamidation of Indole Derivatives with Dianionic Phase-Transfer Catalyst
-
Asymmetric dearomatizing fluorocyclization of indole derivatives was investigated using a dicarboxylate phase-transfer catalyst. This reaction proceeds under mild reaction conditions to provide fluoropyrroloindoline derivatives in a highly enantioselective manner. Various substitution patterns on the indole ring are well tolerated. To facilitate the reaction and ensure reproducibility, the addition of water is essential, and its possible role is discussed.
- Egami, Hiromichi,Hotta, Ryo,Otsubo, Minami,Rouno, Taiki,Niwa, Tomoki,Yamashita, Kenji,Hamashima, Yoshitaka
-
supporting information
p. 5656 - 5660
(2020/07/14)
-
- Substitution of the Dimethylamino Group in Gramines and One-Pot Cyclization to Tetrahydro-β-carbolines Using a Triazine-Based Activating Agent
-
A new method for the substitution of 3-[(dimethylamino)methyl]indoles (gramines) with malonate-based nucleophiles was developed using 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) as the activating agent for the dimethylamino group. The reaction was completed in 1.5-6 h at room temperature in the presence of a tert-amine base and lithium salt. CDMT afforded superior results to methyl iodide, a common activating agent for the dimethylamino group in Mannich bases, particularly in the reactions of 1-substituted gramines. The reactivity of the possible intermediates, bis(indol-3-ylmethyl)dimethylammonium salts, was examined to obtain mechanistic insights on the reaction. This substitution method with CDMT enabled the sequential transformation of gramines: substitution with (N-alkylidene)aminomalonates followed by the Pictet-Spengler reaction under acidic conditions afforded 1,2,3,4-tetrahydro-β-carboline derivatives in one pot.
- Fujita, Hikaru,Nishikawa, Riho,Sasamoto, Ozora,Kitamura, Masanori,Kunishima, Munetaka
-
p. 8380 - 8391
(2019/07/08)
-
- Tryptamine Synthesis by Iron Porphyrin Catalyzed C?H Functionalization of Indoles with Diazoacetonitrile
-
The functionalization of C?H bonds with non-precious metal catalysts is an important research area for the development of efficient and sustainable processes. Herein, we describe the development of iron porphyrin catalyzed reactions of diazoacetonitrile with N-heterocycles yielding important precursors of tryptamines, along with experimental mechanistic studies and proof-of-concept studies of an enzymatic process with YfeX enzyme. By using readily available FeTPPCl, we achieved the highly efficient C?H functionalization of indole and indazole heterocycles. These transformations feature mild reaction conditions, excellent yields with broad functional group tolerance, can be conducted on gram scale, and thus provide a unique streamlined access to tryptamines.
- Hock, Katharina J.,Knorrscheidt, Anja,Hommelsheim, Renè,Ho, Junming,Weissenborn, Martin J.,Koenigs, Rene M.
-
supporting information
p. 3630 - 3634
(2019/02/13)
-
- Photoredox-Catalyzed Cα-H Cyanation of Unactivated Secondary and Tertiary Aliphatic Amines: Late-Stage Functionalization and Mechanistic Studies
-
This paper describes the development and mechanistic studies of a general, high-yielding amine Cα-H cyanation protocol via photoredox catalysis. Inexpensive NaCN is employed as the cyanide source and air is the external oxidant, resulting in mild and highly functional group tolerant conditions. Notably, efficient Cα-H cyanations of secondary and tertiary aliphatic amines and of complex, biologically active compounds (drugs) can be performed using the established methodology. Mechanistic studies suggest that the carboxylic acid additive has three effects: formation of a stabilizing hemiaminal intermediate, prevention of catalyst decomposition by protonating the substrate, and modulation of fluorescence quenching of the photoexcited catalyst species.
- Yilmaz, Ozgur,Oderinde, Martins S.,Emmert, Marion H.
-
p. 11089 - 11100
(2018/09/12)
-
- Synthesis of α-aminonitriles using aliphatic nitriles, α-amino acids, and hexacyanoferrate as universally applicable non-toxic cyanide sources
-
In cyanation reactions, the cyanide source is often directly added to the reaction mixture, which restricts the choice of conditions. The spatial separation of cyanide release and consumption offers higher flexibility instead. Such a setting was used for the cyanation of iminium ions with a variety of different easy-to-handle HCN sources such as hexacyanoferrate, acetonitrile or α-amino acids. The latter substrates were first converted to their corresponding nitriles through oxidative decarboxylation. While glycine directly furnishes HCN in the oxidation step, the aliphatic nitriles derived from α-substituted amino acids can be further converted into the corresponding cyanohydrins in an oxidative C-H functionalization. Mn(OAc)2 was found to catalyze the efficient release of HCN from these cyanohydrins or from acetone cyanohydrin under acidic conditions and, in combination with the two previous transformations, permits the use of protein biomass as a non-toxic source of HCN.
- Nauth, Alexander M.,Konrad, Tim,Papadopulu, Zaneta,Vierengel, Nina,Lipp, Benjamin,Opatz, Till
-
supporting information
p. 4217 - 4223
(2018/09/29)
-
- Synthesis method of tryptamine and derivative thereof
-
The invention discloses a synthesis method of tryptamine and derivative thereof. The method includes the steps of: (1) in the presence of an acid anhydride compound, subjecting chromamine andits derivatives, including the following steps: (1) in the presence of anhydride compounds, and subjecting aryl sulfoxide shown as structural formula (I) and an alpha-tin substituted nitrile compoundshown as structural formula (II) to rearrangement reaction to synthesize an intermediate A shown as structural formula (III); (2) under the action of magnesium powder and alkali, subjecting the intermediate A to alkali hydrolysis to obtain an intermediate B shown as structural formula (IV); (3) in a tetrahydrofuran solution of the intermediate B, and adding triethyl silicane, trimethylchlorosilane and palladium chloride in order for reaction to obtain an intermediate C shown as structural formula (V); and (4) under the action of lithium aluminum hydride, carrying out reduction reaction on theintermediate C so as to obtain tryptamine or derivative thereof shown as structural formula (VI). The method provided by the invention has the advantages of mild reaction conditions, good selectivity, high yield, easy separation of product, simple operation and the like.
- -
-
-
- Corresponding amine nitrile and method of manufacturing thereof
-
The invention relates to a manufacturing method of nitrile. Compared with the prior art, the manufacturing method has the characteristics of significantly reduced using amount of an ammonia source, low environmental pressure, low energy consumption, low production cost, high purity and yield of a nitrile product and the like, and nitrile with a more complex structure can be obtained. The invention also relates to a method for manufacturing corresponding amine from nitrile.
- -
-
-
- Iron nitrate/TEMPO: A superior homogeneous catalyst for oxidation of primary alcohols to nitriles in air
-
A highly practical, one-step, facile synthesis of aromatic, heteroaromatic, allylic and aliphatic nitriles from primary alcohols catalyzed by ferric nitrate [Fe(NO3)3·9H2O] in the presence of TEMPO, aqueous ammonia and air at room temperature is described.
- Dighe, Shashikant U.,Chowdhury, Deepan,Batra, Sanjay
-
p. 3892 - 3896
(2015/01/09)
-
- Synthesis of novel 3,4-diaryl-5-aminopyrazoles as potential kinase inhibitors
-
Synthesis of a diverse series of novel 3,4-diaryl-5-aminopyrazoles as candidates in the development of new protein kinase inhibitors is reported for the first time. In the course of a wider study into bisindolylmaleimide (BIM) derivatives, we examined a novel 5-aminopyrazole heterocyclic moiety as a structural analogue of the highly potent VEGF-R2/3 inhibitor pyrrole-2-one (8). The versatile nature of this pharmacophore allows considerable scope for derivatisation and hence exploration of structure activity relationships. Consequently, a variety of structural modifications were used in order to diversify the aminopyrazole ring substituents. Bicyclic derivatives of the parent aminopyrazoles (11, 12) were also synthesised as a means of probing the kinase active site, leading to formation of complex planar pyrimidine moieties. This work provides the framework for new explorations into kinase inhibition and critical investigations into selectivity of inhibitory activity.
- Pierce, Larry T.,Cahill, Michael M.,McCarthy, Florence O.
-
experimental part
p. 4601 - 4611
(2011/07/08)
-
- Indolyl-3-acetaldoxime dehydratase from the phytopathogenic fungus Sclerotinia sclerotiorum: Purification, characterization, and substrate specificity
-
The purification and characterization of indolyl-3-acetaldoxime dehydratase produced by the plant fungal pathogen Sclerotinia sclerotiorum is described. The substrate specificity indicates that it is an indolyl-3-acetaldoxime dehydratase (IAD, EC 4.99.1.6), which catalyzes transformation of indolyl-3-acetaldoxime to indolyl-3-acetonitrile. The enzyme showed Michaelis-Menten kinetics and had an apparent molecular mass of 44 kDa. The amino acid sequence of IAD, determined using LC-ESI-MS/MS, identified it as the protein SS1G-01653 from S. sclerotiorum. IADSs was highly homologous (84% amino acid identity) to the hypothetical protein BC1G-14775 from Botryotinia fuckeliana B05.10. In addition, similarity to the phenylacetaldoxime dehydratases from Gibberella zeae (33% amino acid identity) and Bacillus sp. (20% amino acid identity) was noted. The specific activity of IADSs increased about 17-fold upon addition of Na2S2O4 under anaerobic conditions, but in the absence of Na2S2O 4 no significant change was observed, whether aerobic or anaerobic conditions were used. As with other aldoxime dehydratases isolated from microbes, the role of IADSs in fungal plant pathogens is not clear, but given its substrate specificity, it appears unlikely that IADSs is a general xenobiotic detoxifying enzyme.
- Pedras, M. Soledade C.,Minic, Zoran,Thongbam, Premila D.,Bhaskar, Vangala,Montaut, Sabine
-
experimental part
p. 1952 - 1962
(2011/06/26)
-
- Remarkable incorporation of the first sulfur containing indole derivative: Another piece in the biosynthetic puzzle of crucifer phytoalexins
-
The first sulfur labelled compound, [2H4, 34S]indolyl-3-acetothiohydroxamic acid, is incorporated into the phytoalexins cyclobrassinin and spirobrassinin and the indole glucosinolate glucobrassicin, indicating that both bi
- Pedras, M. Soledade C.,Okinyo, Denis P. O.
-
-
- Iminyl radicals from α-azido o-iodoanilides via 1,5-H transfer reactions of aryl radicals: New transformation of α-azido acids to decarboxylated nitriles
-
(Chemical Equation Presented) The radical reaction of tributyltin hydride with o-iodo-N-methylanilides derived from α-azido acids provides an excellent access to α-(aminocarbonyl)iminyl radicals through 1,5-hydrogen transfer reaction of initially formed aryl radicals followed by β-elimination of dinitrogen from ensuing α-azido-α- (aminocarbonyl)alkyl radicals. The outcoming iminyls display a peculiar tendency to form corresponding nitriles by β-elimination of aminocarbonyl radicals.
- Bencivenni, Giorgio,Lanza, Tommaso,Leardini, Rino,Minozzi, Matteo,Nanni, Daniele,Spagnolo, Piero,Zanardi, Giuseppe
-
p. 4721 - 4724
(2008/09/21)
-
- Cleavage of alkoxycarbonyl protecting groups from carbamates by t-BuNH2
-
An efficient, simple protocol for the selective cleavage of a variety of N-alkoxycarbonyl protecting groups by t-BuNH2/MeOH is described. The scope of the procedure was explored for a series of indole, aniline and pyrrolidine carbamate derivatives containing other potentially reactive functional groups affording a clean cleavage of the carbamate group.
- Suárez-Castillo, Oscar R.,Montiel-Ortega, Luis Alberto,Meléndez-Rodríguez, Myriam,Sánchez-Zavala, Maricruz
-
-
- NOVEL TRICYCLIC HETEROCYCLE COMPOUND
-
―The present invention relates to the compound represented by formula (I) ????????A―X―Y―Z―B?????(I) (wherein A is a cyclic group which may have a substituent(s); X is a single bond or a spacer; Y is a single bond or a spacer; Z is a single bond or a spacer; B is a hydrocarbon group which may have a substituent(s) or a cyclic group which may have a substituent(s)), a salt thereof, a solvate thereof or a prodrug thereof. The compound represented by formula (I), a salt thereof, a solvate thereof or a prodrug thereof is useful for preventive and/or therapeutic agent for a disease caused by stress.
- -
-
Page/Page column 58
(2008/06/13)
-
- Mapping the melatonin receptor. 7. Subtype selective ligands based on β-substituted N-acyl-5-methoxytryptamines and β-Substituted N-acyl-5-methoxy-1-methyltryptamines
-
A series of β-substituted and β,β-disubstituted N-acyl 5-methoxy-1-methyltryptamines and 5-methoxytryptamines have been prepared as melatonin analogues to investigate the nature of the binding site of the melatonin receptor. The affinity of analogues was determined in a radioligand binding assay using cloned human MT1 and MT2 receptor subtypes expressed in NIH 3T3 cells. Agonist and antagonist potency of all analogues was measured using the pigment aggregation response of a clonal line of Xenopus laevis melanophores, β-Methylmelatonin (17a) and β,β-dimethylmelatonin (17b), though showing a slight decrease in binding at human receptors, show an increase in potency on Xenopus, N-Butanoyl 5-methoxy-1-methyl-β,β-trimethylenetryptamine (12c) is an antagonist at human MT1 receptors but an agonist at MT2, while N-butanoyl 5-methoxy-1-methyl-β,β-tetramethylenetryptamine (13c) is an antagonist at MT1 but had no action at MT2 and is one of the first examples of an MT1 selective antagonist.
- Tsotinis, Andrew,Vlachou, Margarita,Papahatjis, Demetris P.,Calogeropoulou, Theodora,Nikas, Spyros P.,Garratt, Peter J.,Piccio, Vincent,Vonhoff, Stefan,Davidson, Kathryn,Teh, Muy-Teck,Sugden, David
-
p. 3509 - 3519
(2007/10/03)
-
- An efficient method for the N-debenzylation of aromatic heterocycles
-
The N-debenzylation of aromatic heterocycles such as substituted pyrroles and indoles, having functional groups like ester, amide, halo, and nitrile, by using sodium in liquid ammonia in the presence of t-BuOH at -78°C cleanly affords N-debenzylated aromatic heterocycles in good yields.
- Rao, T. Srinivasa,Pandey, Pramod S.
-
p. 3121 - 3127
(2007/10/03)
-
- KINASE INHIBITORS
-
The present invention provides kinase inhibitors of Formula (I)
- -
-
Page/Page column 33
(2010/02/07)
-
- Reactions of substituted 2,3-dihydro-1H-indol-3-ones and pyrrolo[2,3-b]pyridin-3-ones with Wittig and Horner-Emmons reagents: Synthesis of 7-azatryptamine
-
The reactivity of indolinone 1 towards Wittig and Horner-Emmons reactions was reported; the influence of the nature of substituent on the nitrogen atom was examined. 7-Azaindolinone 2 reacted with diethyl cyanomethanephosphonate for giving the corresponding (7-azaindol-3-yl)acetonitrile or more unexpectedly, a C-2 alkylated product; this behavior has been extended to another nucleophilic reagent. Finally the synthesis of 7-azatryptamine was reported.
- Mérour, Jean-Yves,Gadonneix, Philippe,Malapel-Andrieu, Béatrice,Desarbre, Eric
-
p. 1995 - 2002
(2007/10/03)
-
- Simple one step syntheses of indole-3-acetonitriles from indole-3-carboxaldehydes
-
One step conversion method of indole-3-carboxaldehydes into indole-3-acetonitriles is developed. Applying the method, 4-nitro- (7 a), 4-phenyl-(7 b), 4-iodo- (7 c), 4-methoxy- (7 d), and 4-benzyloxyindole-3-acetonitrile (7 e) are available in two steps from indole-3-carboxaldehyde (4).
- Yamada, Fumio,Hashizume, Tomoko,Somei, Masanori
-
p. 509 - 516
(2007/10/03)
-
- Methodology for the efficient synthesis of 3,4-differentially substituted indoles. Fluoride ion-induced elimination-addition reaction of 1-triisopropylsilylgramine methiodides
-
1-Triisopropylsilylgramine methiodide reacted smoothly with a variety of nucleophiles in the presence of tetrabutylammonium fluoride to give 3-substituted indoles. The 3,4-disubstituted indoles were efficiently synthesized by sequential use of 4-selective lithiation of 1-triisopropylsilylgramine and this new substitution reaction.
- Iwao, Masatomo,Motoi, Osamu
-
p. 5929 - 5932
(2007/10/02)
-
- IDENTIFICATION OF 1-METHOXYINDOLYL-3-METHYL ISOTHIOCYANATE AS AN INDOLE GLUCOSINOLATE BREAKDOWN PRODUCT
-
The putative indole glucosinolate enzymic hydrolysis product, 1-methoxyindolyl-3-methyl isothiocyanate has been detected for the first time using low and high resolution mass spectrometry.
- Hanley, A. Bryan,Parsley, Keith R.
-
p. 769 - 771
(2007/10/02)
-
- Chemistry of Indole Glucosinolates: Intermediacy of Indol-3-ylmethyl Isothiocyanates in the Enzymic Hydrolysis of Indole Glucosinolates
-
The enzymic hydrolysis of 1-methoxyindol-3-ylmethyl glucosinolate (1b) proceeds via the corresponding isothiocyanate (2b), thus providing evidence for a previously unsubstantiated breakdown pathway and establishing a link with 1-methoxycyclobrassinin (4b) and related indole phytoalexins.
- Hanley, A. Bryan,Parsley, Keith R.,Lewis, Jenny A.,Fenwick, G. Roger
-
p. 2273 - 2276
(2007/10/02)
-
- A CONVENIENT SYNTHESIS OF TRYPTAMINES
-
Reaction of tosylmethyl isocyanide with substituted formyl indoles gave the nitrile with one more carbon atom.Hydrogenation of this nitrile afforded the corresponding tryptamine.
- Merour, J. Y.,Buzas, A.
-
p. 2331 - 2336
(2007/10/02)
-
- Synthesis and Cycloaddition Reaction of 2-Cyano-3-indoleacetonitriles
-
The reactions of 3-acylindoles with diethyl phosphorocyanidate (DEPC) in the presence of lithium cyanide (LiCN) are described.Treatment of 1 with DEPC and LiCN gave a mixture of (E)- and (Z)-3-cyanomethylene-1-diethylphosphono-2-hydroxyindolines (2 and 3).On the other hand, reaction of 12, 13, and 20a-d with DEPC and LiCN afforded 2-cyano-3-indoleacetonitrile derivatives (16, 19 and 21a-d).Strong base-induced cycloaddition reactions of 2-cyano-1-methyl-3-indoleacetonitrile (21a) with carbon-carbon triple bonds were carried out and gave the corresponding condensation products, 1-amino-4-cyanocarbazoles (22a-e), 6-amino-11-cyanobenzocarbazole (23), pyridocarbazole (25), and pyridocarbazole (26), in moderate yields.Keywords-diethyl phosphorocyanidate; cyanophosphorylation; 3-cyanomethyleneindoline; 2-cyano-3-indoleacetonitrile; orthoquinodimethane; acetylenic dienophile; 1-amino-4-cyano-carbazole; benzocarbazole; pyridocarbazole; pyridocarbazole
- Kurihara, Takushi,Hanakawa, Mitsuko,Harusawa, Shinya,Yoneda, Ryuji
-
p. 4545 - 4553
(2007/10/02)
-