cas 3466-82-8, 2-PHENYL-AZEPANE | Articles data

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Direct access to functionalized azepanes by cross-coupling with α-halo eneformamides
The synthesis of functionalized azepanes was accomplished through the palladium-mediated cross-coupling of α-halo eneformamides with mostly unactivated nucleophiles under mild conditions. Alkenylations proceeded with excellent stereoselectivitiy. In most
Beng, Timothy K.,Wilkerson-Hill, Sidney M.,Sarpong, Richmond
p. 916 - 919
(2014)
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Discovery, synthesis and exploration of N-benzylsulfonyl-2-phenylazepanes as inhibitors of Bim expression in a mouse embryonic fibroblast model
Chronic activation of beta-adrenergic receptors by the sympathetic nervous system results in the apoptosis of cardiomyocytes. Due to the inability of cardiomyocytes to regenerate, this can result in heart failure. Upregulation of the pro-apoptotic protein Bim has been implicated as the cause of cardiomyocyte apoptosis. Beta blockers are the frontline drug used to negate this apoptotic pathway, as no direct inhibitors of Bim expression currently exist. Unfortunately, treatment of heart failure using beta blockers is not optimal. Therefore, direct inhibition of Bim expression is an attractive strategy to provide protection against stress-induced apoptosis of cardiomyocytes. Herein we explore a class of N-benzylsulfonyl-2-phenylazepanes to obtain anti-apoptotic compounds capable of reducing Bim expression levels to 7% of the control at 10 μM in cardiomyocytes under conditions of chronic beta-adrenergic receptor activation with little inhibitory effect upon protein kinase A activity and minimal toxicity.
Abbott, Belinda M.,Dahanayake, Darani,Glab, Jason A.,Mbogo, George W.,Puthalakath, Hamsa,Richards, Benjamin J.,Smith, Brian J.
(2022/02/07)

Direct α-C-H bond functionalization of unprotected cyclic amines
Cyclic amines are ubiquitous core structures of bioactive natural products and pharmaceutical drugs. Although the site-selective abstraction of C-H bonds is an attractive strategy for preparing valuable functionalized amines from their readily available parent heterocycles, this approach has largely been limited to substrates that require protection of the amine nitrogen atom. In addition, most methods rely on transition metals and are incompatible with the presence of amine N-H bonds. Here we introduce a protecting-group-free approach for the α-functionalization of cyclic secondary amines. An operationally simple one-pot procedure generates products via a process that involves intermolecular hydride transfer to generate an imine intermediate that is subsequently captured by a nucleophile, such as an alkyl or aryl lithium compound. Reactions are regioselective and stereospecific and enable the rapid preparation of bioactive amines, as exemplified by the facile synthesis of anabasine and (-)-solenopsin A.
Chen, Weijie,Ma, Longle,Paul, Anirudra,Seidel, Daniel
p. 165 - 169
(2018/02/06)

Chemoenzymatic Synthesis of Substituted Azepanes by Sequential Biocatalytic Reduction and Organolithium-Mediated Rearrangement
Enantioenriched 2-aryl azepanes and 2-arylbenzazepines were generated biocatalytically by asymmetric reductive amination using imine reductases or by deracemization using monoamine oxidases. The amines were converted to the corresponding N′-aryl ureas, which rearranged on treatment with base with stereospecific transfer of the aryl substituent to the 2-position of the heterocycle via a configurationally stable benzyllithium intermediate. The products are previously inaccessible enantioenriched 2,2-disubstituted azepanes and benzazepines.
Zawodny, Wojciech,Montgomery, Sarah L.,Marshall, James R.,Finnigan, James D.,Turner, Nicholas J.,Clayden, Jonathan
supporting information
p. 17872 - 17877
(2019/01/04)

A One-Pot Process for the Enantioselective Synthesis of Amines via Reductive Amination under Transfer Hydrogenation Conditions
(Equation presented) Cyclic amines may be prepared via a sequence of deprotection followed by intramolecular reductive amination of t-Boc-protected amino ketones under asymmetric transfer hydrogenation conditions. In cases where the corresponding imine reaction proceeds with high enantioselectivity, this is reflected in the one-step process.
Williams, Glynn D.,Pike, Richard A.,Wade, Charles E.,Wills, Martin
p. 4227 - 4230
(2007/10/03)

Reduction of imines via titanium-catalyzed hydromagnesation
We have recently discovered that imines can be reduced to amines via a titanium catalyzed hydromagnesation reaction. These reactions employ n-BuMgCl (1.2 eq) as the stoichiometric reducing agent and Cp2TiCl2 (3-5 mol%) as a catalyst. Reactions are run under nitrogen at ambient temperature and pressure. For most aldimine and cyclic ketimine substrates amine products are obtained in yields ranging from 69-94%. The reaction is not tolerant of bulky nitrogen substituents or primary enolizable protons on the imine substrate.
Amin, Sk. Rasidul,Crowe, William E.
p. 7487 - 7490
(2007/10/03)

A convenient preparation of 3-aza-2-phenyl bicyclo[3.2.2]nonane and related 2-substituted cyclic amines
2-Phenylazacycloalkanes are readily prepared by reaction of the corresponding unsubstituted N-chloroamines in diethyl ether with 2.5 equivalents of phenyl lithium.
Healy,Smith,Stemp
p. 3789 - 3797
(2007/10/03)

Pyrroloisoquinoline antidepressants. 2. In-depth exploration of structure-activity relationships
A series of pyrrolo[2,1-a]isoquinolines, and related compounds, were examined for antidepressant-like activity, by virtue of their antagonism of tetrabenazine-induced ptosis and sedation, and inhibition of biogenic amine uptake. Thus, we have identified some of the most potent antagonists of TBZ-induced ptosis and some of the most potent inhibitors of the uptake of dopamine, norepinephrine, and serotonin (in rat brain synaptosomes) ever reported. Compounds of particular note, in this regard, are 52b, 29b, 22b, and 48b, respectively. Biological activity was chiefly manifested by the trans isomeric class. Also, through resolution of four compounds, 7b, 24b, 37b, and 48b, biological activity was found to be associated with the (+) enantiomer subgroup (salts measured at 589 nm in MeOH), corresponding to the 6S,10bR absolute configuration for 7b, 37b, and 48b, and the 6R,10bR configuration for 24b. An X-ray determination on (+)-24b·HBr established its absolute configuration; configurations for the other compounds were verified by enantiospecific synthesis starting with (+)-(R)-2-phenylpyrrolidine. Regarding the pendant phenyl ring, diverse substitution patterns were investigated. Those substitutions that were particularly unfavorable were 3',4',5'-trimethoxy (20b), 2',3',4',5',6'-pentafluoro (34b), 2'-trifluoromethyl (38b), 3',5'-bis(trifluoromethyl) (42b), 4'-n-butyl (44b), 2'-cyano (47b), 4'-methylsulfonyl (50b), and 2'-carboxy (58b). Exceedingly potent compounds, in one way or another, were 10b-12b, 22b, 23b, 25b, 28b, 29b, 33b, 45b, 48b, 51b-53b. The pattern of aromatic substitution had a strong impact on selectivity in the uptake tests (NE vs. DA vs. 5-HT). Activity was significantly diminished by methyl substitution of 7b at the 5 (65, 66), 6 (61b), or 10b (60b) position, by changing the phenyl group of 7b to cyclohexyl (67b), benzyl (68b), or H (72), by moving the phenyl group of 7b to the 5 (69) or 10b (70) position, by expansion of ring B to an azepine (78b), and by modification of ring C to an azetidine (77b), piperidine (75b), or azepine (74b). The interaction of selected analogues with various CNS receptors is reported. Little affinity was shown for the muscarinic cholinergic receptor, suggesting a lack of anticholinergic side effects. Interestingly, 24b and 33b displayed a high affinity for the serotonin-2 receptor, analogous to mianserin and clomipramine. After the body of data was reviewed, derivatives 24b and 48b were chosen for advanced development.
Maryanoff,McComsey,Gardocki,Shank,Costanzo,Nortey,Schneider,Setler
p. 1433 - 1454
(2007/10/02)

A NEW SYNTHESIS OF IMIDOYL IODIDES VIA BECKMANN REARRANGEMENT OF OXIME SULFONATES
A new synthetic method of imidoyl iodides has been devised which involves the Beckmann rearrangement of oxime derivatives with trimethylsilyl iodide or diethylaluminum iodide.This allows a one-pot procedure for α-arylation of amines in synthetically usefu
Ishida, Yasuko,Sasatani, Satoru,Maruoka, Keiji,Yamamoto, Hisashi
p. 3255 - 3258
(2007/10/02)