132871-11-5Relevant articles and documents
Catalytic Asymmetric Synthesis of Morpholines. Using Mechanistic Insights to Realize the Enantioselective Synthesis of Piperazines
Lau, Ying Yin,Zhai, Huimin,Schafer, Laurel L.
, p. 8696 - 8709 (2016/10/14)
An efficient and practical catalytic approach for the enantioselective synthesis of 3-substituted morpholines through a tandem sequential one-pot reaction employing both hydroamination and asymmetric transfer hydrogenation reactions is described. Starting from ether-containing aminoalkyne substrates, a commercially available bis(amidate)bis(amido)Ti catalyst is utilized to yield a cyclic imine that is subsequently reduced using the Noyori-Ikariya catalyst, RuCl [(S,S)-Ts-DPEN] (η6-p-cymene), to afford chiral 3-substituted morpholines in good yield and enantiomeric excesses of >95%. A wide range of functional groups is tolerated. Substrate scope investigations suggest that hydrogen-bonding interactions between the oxygen in the backbone of the ether-containing substrate and the [(S,S)-Ts-DPEN] ligand of the Ru catalyst are crucial for obtaining high ee's. This insight led to a mechanistic proposal that predicts the observed absolute stereochemistry. Most importantly, this mechanistic insight allowed for the extension of this strategy to include N as an alternative hydrogen bond acceptor that could be incorporated into the substrate. Thus, the catalytic, enantioselective synthesis of 3-substituted piperazines is also demonstrated.
GLYCINE TRANSPORTER-1 INHIBITORS
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Page/Page column 78-79, (2009/07/17)
The present invention provides compounds that are glycine transporter 1 (hereinafter referred to as GlyT-1) inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of GlyT1 such as cognitive disorders associated with Schizophrenia, ADHD (attention deficit hyperactivity disorder), MCI (mild cognitive impairment), and the like. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
Structure-activity relationships of novel, highly potent, selective, and orally active CCR1 antagonists
Xie, Yun Feng,Lake, Kirk,Ligsay, Kathleen,Komandla, Mallareddy,Sircar, Ila,Nagarajan, Gobi,Li, Jian,Xu, Kui,Parise, Jason,Schneider, Lisa,Huang, Ding,Liu, Juping,Dines, Kevin,Sakurai, Naoki,Barbosa, Miguel,Jack, Rick
, p. 3367 - 3372 (2008/02/07)
Design and synthesis of a series of 3-amino-4-(2-(2-(4-benzylpiperazin-1-yl)-2-oxoethoxy)phenylamino)cyclobutenedione derivatives as novel CCR1 antagonists are described. Structure-activity relationship studies led to the identification of compound 22, which demonstrated potent binding activity, functional antagonism of CCR1 as well as good species cross-reactivity. In addition, compound 22 also showed desirable pharmacokinetic profiles and was selected for in vivo studies in the mouse collagen-induced arthritis model.
DUAL NK1/NK3 ANTAGONISTS FOR TREATING SCHIZOPHRENIA
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Page 290-291, (2008/06/13)
The use of compounds of the general formula wherein the substituents are as described in claim 1 or pharmaceutically active acid-addition salts thereof for the preparation of medicaments for the treatment of schizophrenia.
A novel and facile method to synthesize (R)- and (S)-2-methylpiperazine
Liu, Bo,Xu, Guang-Yu,Yang, Chun-Hao,Wu, Xi-Han,Xie, Yu-Yuan
, p. 4111 - 4118 (2007/10/03)
A concise and efficient synthesis of (R)- and (S)-2-methylpiperazine in only five steps from (D)- and (L)-alanine is described. The key step is reaction of benzylamine with a bifunctional molecule to build a six-membered ring.
Substituted piperazines
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, (2008/06/13)
Compounds are provided that act as potent antagonists of the CCR1 receptor, and which have been further confirmed in animal testing for inflammation, one of the hallmark disease states for CCR1. The compounds are generally aryl piperazine derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR1-mediated diseases, and as controls in assays for the identification of competitive CCR1 antagonists.
Asymmetric Synthesis of 2,6-Methylated Piperazines
Mickelson, John W.,Belonga, Kenneth L.,Jacobsen, Jon E.
, p. 4177 - 4183 (2007/10/02)
The complete series of enantiopure 2,6-methylated piperazines was synthesized utilizing two alternative reactions in the key bond-forming step.The dimethyl enantiomers, (2R,6R)- and (2S,6S)-2,6-dimethylpiperazine (1, 2), were prepared using either a diastereoselective triflate alkylation or a novel intermolecular Mitsunobu reaction to set the required stereochemistry.The monomethyl derivatives, (R)- and (S)-tert-butyl 2-methyl-1-piperazinecarboxylate (3, 4) were also synthesized employing the Mitsunobu cyclization strategy while the trimethyl compounds, (R)- and (S)-2,2,6- trimethylpiperazine (5, 6) were prepared using an enantiospecific triflate alkylation as the principal reaction.These methods represent efficient, general strategies for preparing a variety of 2,6-methylated piperazines for which the absolute stereochemistry can be readily controlled.
