347368-07-4Relevant articles and documents
A segmented flow platform for on-demand medicinal chemistry and compound synthesis in oscillating droplets
Hwang, Ye-Jin,Coley, Connor W.,Abolhasani, Milad,Marzinzik, Andreas L.,Koch, Guido,Spanka, Carsten,Lehmann, Hansjoerg,Jensen, Klavs F.
, p. 6649 - 6652 (2017/07/10)
We report an automated flow chemistry platform that can efficiently perform a wide range of chemistries, including single/multi-phase and single/multi-step, with a reaction volume of just 14 μL. The breadth of compatible chemistries is successfully demonstrated and the desired products are characterized, isolated, and collected online by preparative HPLC/MS/ELSD.
Transamidation of carboxamides with amines over nanosized zeolite beta under solvent-free conditions
Durgaiah, Chevella,Naresh, Mameda,Swamy, Peraka,Srujana, Kodumuri,Rammurthy, Banothu,Narender, Nama
, p. 29 - 32 (2016/05/02)
A highly efficient approach to transamidation of carboxamides with amines over nanosized zeolite beta under solvent-free conditions has been successfully demonstrated. Transamidation of a variety of amides with amines produced the respective N-alkyl amides in moderate to excellent yields.
A Heterogeneous Niobium(V) Oxide Catalyst for the Direct Amidation of Esters
Ali, Md. Ayub,Siddiki, S. M. A. Hakim,Kon, Kenichi,Shimizu, Ken-Ichi
, p. 2705 - 2710 (2015/09/15)
This study reports the first example of a heterogeneous catalytic system for the direct amidation of various esters with amines. Of 25 types of catalyst, Nb2O5 shows the highest activity in the amidation of methyl benzoate with aniline. Nb2O5 gives high yields in the amidation of various esters and amines under solvent-free conditions, is reusable, and shows higher turnover numbers than previously reported homogeneous catalysts such as La(OTf)3. IR spectroscopic studies of ethyl acetate adsorbed on the catalysts show a strong acid-base interaction between the Nb5+ Lewis acid site and carbonyl oxygen, which can result in high reactivity of the ester with a nucleophile (amine) and, thus, high activity of Nb2O5. Kinetic results show that the activity of Nb2O5 does not markedly decrease with increasing aniline concentration, in contrast to reference catalysts TiO2 and La(OTf)3. The relatively low negative impact of basic molecules on the Lewis acid catalysis of Nb2O5 also enables its high activity.
Catalytic amidation of unactivated ester derivatives mediated by trifluoroethanol
Caldwell, Nicola,Jamieson, Craig,Simpson, Iain,Watson, Allan J. B.
supporting information, p. 9495 - 9498 (2015/06/08)
A catalytic amidation method has been developed, employing 2,2,2-trifluoroethanol to facilitate condensation of unactivated esters and amines, enabling the synthesis of a range of amide products in good to excellent yields. Mechanistic studies indicate the reaction proceeds through a trifluoroethanol-derived active ester intermediate.
B(OCH2CF3)3-mediated direct amidation of pharmaceutically relevant building blocks in cyclopentyl methyl ether
Karaluka, Valerija,Lanigan, Rachel M.,Murray, Paul M.,Badland, Matthew,Sheppard, Tom D.
supporting information, p. 10888 - 10894 (2015/11/17)
The use of B(OCH2CF3)3 for mediating direct amidation reactions of a wide range of pharmaceutically relevant carboxylic acids and amines is described, including numerous heterocycle-containing examples. An initial screen of solvents for the direct amidation reaction suggested that cyclopentyl methyl ether, a solvent with a very good safety profile suitable for use over a wide temperature range, was an excellent replacement for the previously used solvent acetonitrile. Under these conditions amides could be prepared from 18 of the 21 carboxylic acids and 18 of the 21 amines examined. Further optimisation of one of the low yielding amidation reactions (36% yield) via a design of experiments approach enabled an 84% yield of the amide to be obtained.
Studies on pyrazine derivatives, XLV: Synthesis, reactions, and tuberculostatic activity of N-methyl-N′-(pyrazine-2-carbonyl)- hydrazinecarbodithioic acid methyl ester
Gobis, Katarzyna,Foks, Henryk,Zwolska, Zofia,Augustynowicz-Kopec, Ewa
, p. 965 - 975 (2007/10/03)
Methyldithiocarbonyl derivative 2 of pyrazine-2-carboxylic acid N′-methylhydrazide 1 was synthesized by methylation of CS2 adduct. Benzylamine caused the decomposition of compound 2 to pyrazine-2-carboxylic acid benzylamide 5 and 1,3-dibenzylthiourea, 6. N-methyl-N'′-(pyrazine-2-carbonyl)-hydrazinecarbodithioic acid methyl ester 2 were evidenced to cyclize to 3-methyl-5-pyrazin-2-yl-3H-[1,3,4] oxadiazole-2-thione 8 in the presence of triethylamine. In the reactions with secondary amines such as morpholine, pyrrolidine and phenylpiperazine pyrazinoyl derivatives (9-11) of thiosemicarbazide were obtained. Hydrazine, methylhydrazine, aminoalcohols, and N-alkylamino-substituted cyclic amines reacted with cyclization to 4-substituted 1,2,4-triazole-3-thiones 12, 13, and 18-22. Synthesized compounds exhibited low tuberculostatic activity in vitro (MIC 50-100 μg/mL). Copyright Taylor & Francis Group, LLC.
Enhancing Reductive Cleavage of Aromatic Carboxamides
Ragnarsson, Ulf,Grehn, Leif,Maia, Hernani L. S.,Monteiro, Luis S.
, p. 2021 - 2022 (2007/10/03)
(matrix presented) A set of aromatic and especially heteroaromatic N-benzyl carboxamides, derived from naphthalene, pyridine, pyrazine, and quinoline, and the corresponding tert-butyl acylcarbamates have been synthesized and studied by cyclic voltammetry with respect to facilitated reduction. The latter undergo regiospecific cleavage of their C(O)-N bonds under very mild reductive conditions with formation of Boc-protected (benzyl)-amine in most cases in nearly quantitative yields. Examples of preparative cleavage by controlled potential electrolysis, activated aluminum, and NaBH4 are given.
Amino acid derivatives with anticonvulsant activity
Paruszewski,Strupinska,Stables,Swiader,Czuczwar,Kleinrok,Turski
, p. 629 - 631 (2007/10/03)
A series of benzylamides of N-alkylated, N-acylated or free nine cyclic and one linear amino acids as potential anticonvulsants have been synthesized. The structures of the obtained compounds were designed on the basis of the previously determined structure and physicochemical properties/anticvonvulsant activity relationship of the formerly synthesized compounds of this type. The obtained compounds were evaluated in mice after intraperitoneal (ip) administration, by maximal electroshock seizure test (MES test), subcutaneous (sc) pentylenetetrazol test (sc PTZ test) and by the rotarod neurotoxicity test (Tox test). The results were the basis for their classification into one of three classes of the Anticonvulsant Screening Project (ASP) of the Antiepileptic Drug Development Program (ADDP) of the NIH. Three selected compounds were tested quantitatively in rats after oral administration. The MES ED50, sc PTZ ED50, Tox TD50 were determined and their protective index (PI) values were calculated. Anticonvulsant activity of the most promising compound (15) was examined in different seizure models. The respective ED50 and PI values of this compound were as follows: against bicuculline, 73 and 1.4; against PTZ, 47 and 2.2; against strychnine, 73 and 1.4; against pilocarpine 156, and 0.7; against kainic acid (2-carboxy-4-isopropenyl-3-pyrrolidineacetic acid), 39 and 2.6; against AMPA (α-amino-3-hydroxy-5methyl-4-isoxazolepropionic acid), 10 and 10.3 and against NMDA (N-methyl-D-Aspartic acid), 114 and 0.9.
