95141-79-0Relevant academic research and scientific papers
Palladium-Catalyzed C(sp3)?H Arylation of Primary Amines Using a Catalytic Alkyl Acetal to Form a Transient Directing Group
St John-Campbell, Sahra,Ou, Alex K.,Bull, James A.
supporting information, p. 17838 - 17843 (2018/11/23)
C?H Functionalization of amines is a prominent challenge due to the strong complexation of amines to transition metal catalysts, and therefore typically requires derivatization at nitrogen with a directing group. Transient directing groups (TDGs) permit C?H functionalization in a single operation, without needing these additional steps for directing group installation and removal. Here we report a palladium catalyzed γ-C?H arylation of amines using catalytic amounts of alkyl acetals as transient activators (e.g. commercially available (2,2-dimethoxyethoxy)benzene). This simple additive enables arylation of amines with a wide range of aryl iodides. Key structural features of the novel TDG are examined, demonstrating an important role for the masked carbonyl and ether functionalities. Detailed kinetic (RPKA) and mechanistic investigations determine the order in all reagents, and identify cyclopalladation as the turnover limiting step. Finally, the discovery of an unprecedented off-cycle free-amine directed ?-cyclopalladation of the arylation product is reported.
Site-selective C-H arylation of primary aliphatic amines enabled by a catalytic transient directing group
Liu, Yongbing,Ge, Haibo
, p. 26 - 32 (2017/03/21)
Transition-metal-catalysed direct C-H bond functionalization of aliphatic amines is of great importance in organic and medicinal chemistry research. Several methods have been developed for the direct sp 3 C-H functionalization of secondary and tertiary aliphatic amines, but site-selective functionalization of primary aliphatic amines in remote positions remains a challenge. Here, we report the direct, highly site-selective γ-arylation of primary alkylamines via a palladium-catalysed C-H bond functionalization process on unactivated sp 3 carbons. Using glyoxylic acid as an inexpensive, catalytic and transient directing group, a wide array of γ-arylated primary alkylamines were prepared without any protection or deprotection steps. This approach provides straightforward access to important structural motifs in organic and medicinal chemistry without the need for pre-functionalized substrates or stoichiometric directing groups and is demonstrated here in the synthesis of analogues of the immunomodulatory drug fingolimod directly from commercially available 2-amino-2-propylpropane-1,3-diol.
Discovery of highly potent renin inhibitors potentially interacting with the S3' subsite of renin
Sun, Xiaowei,Wen, Xiaoan,Chen, Yan-Yan,Shi, Chen,Gao, Chengzhe,Wu, Yong,Wang, Li-Jun,Yang, Xiu-Hong,Sun, Hongbin
, p. 269 - 288 (2015/09/21)
To exploit the S3′ subsite of renin active site for renin inhibitor design, 42 aliskiren derivatives with modified P2' portion were designed, synthesized and biologically evaluated. Some highly potent renin inhibitors (IC50 50 Combining double low line 0.9 nM) and 39 (IC50 Combining double low line 0.7 nM) were over 2.5-fold more potent than aliskiren (IC50 Combining double low line 2.3 nM). SAR analysis indicated that incorporation of polar hydrophilic moieties into the P2' portion of renin inhibitors generally enhanced the potency. Consistently with this, molecular modeling study revealed that the triazole part of 39 could provide additional interactions to the S3' subsite of renin active site. Moreover, in vivo evaluation in the double transgenic mouse hypertension model demonstrated that 39 produced greater reduction of the mean arterial blood pressure than ariskiren at the doses of 17.0 and 34.0 1/4mol/kg, respectively. Taken together, the S3' subsite of renin active site merits further consideration for renin inhibitor design.
Copper-catalyzed aliphatic C-H amination with an amidine moiety
Chen, Hui,Sanjaya, Stephen,Wang, Yi-Feng,Chiba, Shunsuke
supporting information, p. 212 - 215 (2013/04/23)
A method for amination of aliphatic C-H bonds of N-alkylamidines is described that utilizes Cu(OAc)2 as the catalyst in the presence of PhI(OAc)2 and K3PO4. The resulting products, dihydroimidazoles and tetrahydropyrimidines, could be converted into the corresponding diamines by hydride reduction.
Substituted indolizine-like compounds and methods of use
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, (2008/06/13)
Selected novel substituted indolizine-like compounds are effective for treatment of diseases, such as TNF-α, IL-1β, IL-6 and/or IL-8 mediated diseases, and other maladies, such as cancer, pain and diabetes. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for treatment of diseases and other maladies or conditions involving inflammation, cancer, pain, diabetes and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
Substituted pyridine and pyridazine compounds and methods of use
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, (2008/06/13)
Selected novel substituted pyridine and pyridazine compounds are effective for prophylaxis and treatment of diseases, such as TNF-α, IL-1β, IL-6 and/or IL-8 mediated diseases, and other maladies, such as cancer, pain and diabetes. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving inflammation, cancer, pain, diabetes and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
