544708-10-3Relevant academic research and scientific papers
Asymmetric synthesis of 3-substituted tetrahydro-2-benzazepines
Quick, Matthias P.,Fr?hlich, Roland,Schepmann, Dirk,Wünsch, Bernhard
, p. 7265 - 7281 (2015/07/01)
The enantiomerically and diastereomerically pure tricyclic oxazolidine cis-10 was prepared in a five step synthesis starting with 1-bromo-2-iodobenzene. Me3SiCN and allylSiMe3 reacted with cis-10 in the presence of TiCl4 to form the nitrile (3S)-11 and the allyl derivative (3S)-12 with high diastereoselectivity. The hydrogenolytic removal of the chiral auxiliary failed, since the endocyclic benzyl-N-bond was cleaved simultaneously. Therefore the N-(hydroxyethyl)amide of (3S)-12 was transformed into the enamide 27, which was hydrolyzed to afford the secondary amide 28. The enamide strategy to remove the chiral auxiliary from (3S)-11 led to complete racemization due to fast deprotonation in α-position of the cyano moiety. Two pairs of enantiomers 30a-b/ent-30a-b with prototypical σ substituents at the N-atom were prepared. The low σ1 affinity of the tetrahydro-2-benzazepines (ent-30b, Ki = 407 nM) is attributed to the short distance between the two lipophilic aromatic moieties.
(3R,11aR)-3-Phenyl-2,3,11,11a-tetrahydro-[1,3]oxazolo[3,2-b]-[2]benzazepin-5(10H)-one as a chiral building block for the asymmetric synthesis of 3-substituted 2-benzazepines
Quick, Matthias P.,Froehlich, Roland,Wuensch, Bernhard
scheme or table, p. 524 - 526 (2010/07/20)
A five-step synthesis of the chiral building block cis-2 is described. Key steps in the synthesis were a Heck reaction of 1-bromo-2-iodobenzene with allyl alcohol, the introduction of a carboxy group after Br/Li-exchange, and the diastereoselective format
Synthesis and SAR studies of 3-substituted 1′-benzylspiro[[2]benzoxepine1,4′-piperidines]
Maier, Christoph A.,Wuensch, Bernhard
, p. 714 - 720 (2007/10/03)
The preparation of the hitherto unknown spiro[[2]benzoxepine-1,4′-piperidine] ring system is described. The synthesis consists of a Wittig reaction of 2-bromobenzaldehyde (4) and (1,3-dioxolan-2-ylmethyl)triphenylphosphonium bromide (5) to yield an α,β-unsaturated acetal. The double bond of 6 was subsequently hydrogenated. The resulting brominated acetal 7 was treated with n-butyllithium and then with 1-benzylpiperidin-4-one (9) to yield the hydroxy acetal 10. Acid-catalyzed cyclization of 10 with p-toluenesulfonic acid or aqueous HCl resulted in the formation of the 1′-benzylspiro[[2]benzoxepine-1,4′-piperidines] 11 and 12, respectively. The substituents in the 3-position of the spiro compounds 11 and 12 were further modified by reaction with trimethylsilyl cyanide or (cyanomethylene)triphenylphosphorane in order to introduce residues with one or two carbon atoms, respectively. The synthesized compounds were evaluated for σ1- and σ2-receptor affinity in vitro. The most potent σ1-ligand was the methoxy derivative 11 (Ki = 2.56 nM), whereas the cyanomethyl derivative 20 turned out to be the most σ1-selective compound (σ1/σ2 selectivity 768). Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
