74591-94-9Relevant academic research and scientific papers
Palladium-catalysed anti-Markovnikov selective oxidative amination
Kohler, Daniel G.,Gockel, Samuel N.,Kennemur, Jennifer L.,Waller, Peter J.,Hull, Kami L.
, p. 333 - 340 (2018/02/27)
In recent years, the synthesis of amines and other nitrogen-containing motifs has been a major area of research in organic chemistry because they are widely represented in biologically active molecules. Current strategies rely on a multistep approach and require one reactant to be activated prior to the carbon-nitrogen bond formation. This leads to a reaction inefficiency and functional group intolerance. As such, a general approach to the synthesis of nitrogen-containing compounds from readily available and benign starting materials is highly desirable. Here we present a palladium-catalysed oxidative amination reaction in which the addition of the nitrogen occurs at the less-substituted carbon of a double bond, in what is known as anti-Markovnikov selectivity. Alkenes are shown to react with imides in the presence of a palladate catalyst to generate the terminal imide through trans-aminopalladation. Subsequently, olefin isomerization occurs to afford the thermodynamically favoured products. Both the scope of the transformation and mechanistic investigations are reported.
Synthesis and evaluation of N-alkyl-S-[3-(piperidin-1-yl)propyl] isothioureas: High affinity and human/rat species-selective histamine H 3 receptor antagonists
Harusawa, Shinya,Sawada, Koichi,Magata, Takuji,Yoneyama, Hiroki,Araki, Lisa,Usami, Yoshihide,Hatano, Kouta,Yamamoto, Kouichi,Yamamoto, Daisuke,Yamatodani, Atsushi
, p. 6415 - 6420 (2013/11/19)
S-Alkyl-N-alkylisothiourea compounds containing various cyclic amines were synthesized in the search for novel nonimidazole histamine H3 receptor (H3R) antagonists. Among them, four N-alkyl S-[3-(piperidin-1-yl)propyl]isothioureas 18, 19, 22, and 23 were found to exhibit potent and selective H3R antagonistic activities against in vitro human H3R, but were inactive against in vitro human H 4R. Furthermore, three alkyl homologs 18-20 showed inactivity for histamine release in in vivo rat brain microdialysis, suggesting differences in antagonist affinities between species. In addition, in silico docking studies of N-[4-(4-chlorophenyl)butyl]-S-[3-piperidin-1-yl)propyl]isothiourea 19 and a shorter homolog 17 with human/rat H3Rs revealed that structural differences between the antagonist-docking cavities of rat and human H 3Rs were likely caused by the Ala122/Val122 mutation.
Convenient route to primary (Z)-allyl amines and homologs
Gerpe, Alejandra,Bollini, Mariela,Gonzalez, Mercedes,Cerecetto, Hugo
experimental part, p. 29 - 47 (2009/04/06)
A convenient two-step procedure for the synthesis of primary (Z)-allyl amines, (Z)-homoallyl amines [(Z)-but-3-enylamines], and (Z)-pent-4-enylamines using the Wittig reaction was achieved. The use of nonstabilized ylides from triphenylphosphonium salt, potassium salt, and apolar solvent produced (Z/E)-geometric isomer ratios generally greater than 1.6. The amine moiety was masked using a phtalimide group that was removed successfully in the last step of the process in two different conditions, NH2NH2/EtOH/rt or CH3NH2/EtOH/rt. However, in some cases, reduction of the C = C double bond in the deprotection with hydrazine was concomitantly observed. Copyright Taylor & Francis Group, LLC.
Bronsted acid-catalyzed intramolecular hydroamination of protected alkenylamines. Synthesis of pyrrolidines and piperidines.
Schlummer, Bjoern,Hartwig, John F
, p. 1471 - 1474 (2007/10/03)
[reaction: see text]. The cyclization of aminoalkenes bearing an electron-withdrawing group on the nitrogen atom was catalyzed by triflic or sulfuric acid in toluene. Pyrrolidines and piperidines were formed in excellent yields. N-phenylanilides also underwent cyclization to form gamma-lactams.
Synthesis and pharmacological characterization of novel 6-fluorochroman derivatives as potential 5-HT(1A) receptor antagonists
Yasunaga, Tomoyuki,Kimura, Takenori,Naito, Ryo,Kontani, Toru,Wanibuchi, Fumikazu,Yamashita, Hiroshi,Nomura, Tamako,Tsukamoto, Shin-Ichi,Yamaguchi, Tokio,Mase, Toshiyasu
, p. 2765 - 2778 (2007/10/03)
A series of novel 6-fluorochroman derivatives was prepared and evaluated as antagonists for the 5-HT(1A) receptor. N-2-[[(6-Fluorochroman-8- yl)oxy]ethyl]-4-(4-methoxyphenyl)butylamine (3; J. Med. Chem. 1997, 40, 1252- 1257) was chosen as a lead, and structural modifications were done on the aliphatic portion of the chroman ring, the tether linking the middle amine and the terminal aromatic ring, the aromatic ring, and lastly the amine. Radioligand binding assays proved that the majority of the novel compounds behaved as good to excellent ligands at the 5-HT(1A) receptor, some of which were selective with respect to α1-adrenergic and D2-dopaminergic receptors. The antagonist activity of the compounds was assessed in the forskolinstimulated adenylate cyclase assays in CHO cells expressing the human 5-HT(1A) receptors. Among the modifications attempted, introduction of an oxo or an optically active hydroxy moiety at the chroman C-4 position was effective in ameliorating the receptor selectivity. Six analogues were selected through the in vitro screens and further evaluated for their in vivo activities. A 4-oxochroman derivative (31n), having a terminal 1,3- benzodioxole ring, demonstrated antagonist activities toward 8-OH-DPAT- induced behavioral and electrophysiological responses in rats.
Role of the Through-Space 2p-3d Overlap Effect in the Wittig Reaction
McEwen, William E.,Cooney, John V.
, p. 983 - 987 (2007/10/02)
Reactions of the ylide derived from triphenyl(3-phthalimidopropyl)phosphonium bromide with aromatic aldehydes have been reported to give exclusively the Z alkenes.On the basis of the Bestmann mechanism for the Wittig reaction, and also because of the fact that a 2,6-dimethoxyphenyl group enters into a strong through-space 2p-3d overlap interaction with an adjacent phosphonio group, we postulated that the reactions of the ylide derived from (2,6-dimethoxyphenyl)diphenyl(3-phthalimidopropyl)phosphonium bromide with aromatic aldehydes would give substantial ratios of E:Z alkenes.This proved to be the case.
