- Contra-thermodynamic Hydrogen Atom Abstraction in the Selective C-H Functionalization of Trialkylamine N-CH3 Groups
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We report a simple one-pot protocol that affords functionalization of N-CH3 groups in N-methyl-N,N-dialkylamines with high selectivity over N-CH2R or N-CHR2 groups. The radical cation DABCO+?, prepared in situ by oxidation of DABCO with a triarylaminium salt, effects highly selective and contra-thermodynamic C-H abstraction from N-CH3 groups. The intermediates that result react in situ with organometallic nucleophiles in a single pot, affording novel and highly selective homologation of N-CH3 groups. Chemoselectivity, scalability, and recyclability of reagents are demonstrated, and a mechanistic proposal is corroborated by computational and experimental results. The utility of the transformation is demonstrated in the late-stage site-selective functionalization of natural products and pharmaceuticals, allowing rapid derivatization for investigation of structure-activity relationships.
- Barham, Joshua P.,John, Matthew P.,Murphy, John A.
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supporting information
p. 15482 - 15487
(2016/12/09)
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- HETEROARYL DERIVATIVES
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Compounds of formula (I) described herein are both phosphodiesterase 4 (PDE4) enzyme inhibitors and muscarinic M3 receptor antagonists and are useful for the prevention and/or treatment of diseases of the respiratory tract characterized by airway obstruction.
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Paragraph 0506; 0507
(2015/06/17)
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- HETEROARYL DERIVATIVES FOR THE TREATMENT OF RESPIRATORY DISEASES
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The invention relates to novel compounds of formula (I) which are both phosphodiesterase 4 (PDE4) enzyme inhibitors and muscarinic M3 receptor antagonists, methods of preparing such compounds, compositions containing them and therapeutic use thereof.
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Page/Page column 118; 119
(2015/06/18)
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- Synthesis and sigma receptor binding affinities of 8-azabicyclo[3.2.1]octan-3α-yl and 9-azabicyclo[3.3.1]nonan-3α-yl phenylcarbamates
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A series of N-(8-benzyl-8-azabicyclo[3.2.1]octan-3α-yl)carbamates and N-(9-benzyl-9-azabicyclo[3.3.1]nonan-3α-yl)carbamates was prepared and their affinities for sigma (σ1 and σ2) and serotonin 5-HT3 and 5-HT4 receptors was measured in vitro. The results of this structure-activity relationship study identified a novel compound, N-(9-benzyl-9-aza-bicyclo[3.3.1]nonan-3α-yl)N′- (2-methoxy-5-methylphenyl)carbamate (4i), having a high affinity and moderate selectivity for σ2 versus σ1 receptors and a low affinity for 5-HT3 and 5-HT4 receptors. The results of this structure-activity relationship study should provide valuable information for the preparation of σ2-selective ligands that can be used to further characterize the functional role of this receptor in vivo.
- Mach,Yang,Wu,Kuhner,Whirrett,West
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p. 339 - 355
(2007/10/03)
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- Synthesis and microbial hydroxylation of some azabicycloalkanes
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N-Substituted 7-azabicyclo[2.2.1]heptanes have been synthesized in a short route. These compounds containing benzamide or benzenesulfonamide groups are good substrates for microbial oxidation of unactivated carbons by B. bassiana.
- Olivo, Horacio F.,Hemenway, Michael S.,Gezginci, Mikail H.
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p. 1309 - 1312
(2007/10/03)
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