771-51-7Relevant articles and documents
Lewis acid catalyzed nitrile synthesis from aldehyde
Bariya, Dipakkumar,Mishra, Satyendra
supporting information, (2022/03/16)
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
Fe-catalyzed Fukuyama-type indole synthesis triggered by hydrogen atom transfer
Huang, Hanmin,Yu, Min,Zhang, Tianze
, p. 10501 - 10505 (2021/08/20)
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
N-skatyltryptamines-dual 5-ht6r/d2r ligands with antipsychotic and procognitive potential
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
, (2021/08/17)
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.
Iron-Catalyzed α-C-H Cyanation of Simple and Complex Tertiary Amines
Yilmaz, Ozgur,Dengiz, Cagatay,Emmert, Marion H.
supporting information, p. 2489 - 2498 (2021/02/06)
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.
Asymmetric Dearomatizing Fluoroamidation of Indole Derivatives with Dianionic Phase-Transfer Catalyst
Egami, Hiromichi,Hotta, Ryo,Otsubo, Minami,Rouno, Taiki,Niwa, Tomoki,Yamashita, Kenji,Hamashima, Yoshitaka
supporting information, p. 5656 - 5660 (2020/07/14)
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.
Tryptamine Synthesis by Iron Porphyrin Catalyzed C?H Functionalization of Indoles with Diazoacetonitrile
Hock, Katharina J.,Knorrscheidt, Anja,Hommelsheim, Renè,Ho, Junming,Weissenborn, Martin J.,Koenigs, Rene M.
supporting information, p. 3630 - 3634 (2019/02/13)
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.
Substitution of the Dimethylamino Group in Gramines and One-Pot Cyclization to Tetrahydro-β-carbolines Using a Triazine-Based Activating Agent
Fujita, Hikaru,Nishikawa, Riho,Sasamoto, Ozora,Kitamura, Masanori,Kunishima, Munetaka
, p. 8380 - 8391 (2019/07/08)
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.
Photoredox-Catalyzed Cα-H Cyanation of Unactivated Secondary and Tertiary Aliphatic Amines: Late-Stage Functionalization and Mechanistic Studies
Yilmaz, Ozgur,Oderinde, Martins S.,Emmert, Marion H.
, p. 11089 - 11100 (2018/09/12)
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.
Synthesis of α-aminonitriles using aliphatic nitriles, α-amino acids, and hexacyanoferrate as universally applicable non-toxic cyanide sources
Nauth, Alexander M.,Konrad, Tim,Papadopulu, Zaneta,Vierengel, Nina,Lipp, Benjamin,Opatz, Till
supporting information, p. 4217 - 4223 (2018/09/29)
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.
Corresponding amine nitrile and method of manufacturing thereof
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, (2018/05/07)
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.
