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6 results on '"Ilias Dorziotis"'

1. Synthesis of a Muscarinic Receptor Antagonist via a Diastereoselective Michael Reaction, Selective Deoxyfluorination and Aromatic Metal−Halogen Exchange Reaction

Author

David M. Tschaen, Thoa Hoang, Yoshiaki Kato, Atsushi Akao, Joseph J. Lynch, Audrey Molina, Takayuki Nemoto, Koji Tomimoto, Ralph P. Volante, Toshiaki Mase, Daniel Zewge, Fengrui Lang, Paul J. Reider, Takehiko Iida, Toshihiro Wada, Keisuke Kamei, Shinji Kato, Jaemoon Lee, Takahiro Itoh, Ilias Dorziotis, Peter E. Maligres, Khateeta M. Emerson, Shigemitsu Okada, Masashi Kawasaki, Jake Z. Song, Ioannis N. Houpis, and Robert A. Reamer

Subjects
Receptor, Muscarinic M3, chemistry.chemical_classification, Ketone, Hydrocarbons, Fluorinated, Chemistry, Stereochemistry, Metalation, Organic Chemistry, Stereoisomerism, Muscarinic Antagonists, Amides, Receptors, Muscarinic, Combinatorial chemistry, Reductive amination, chemistry.chemical_compound, Dioxolane, Michael reaction, Animals, Humans, Moiety, Amine gas treating, Amination
Abstract

An efficient synthesis of a structurally unique, novel M(3) antagonist 1 is described. Compound 1 is conveniently disconnected retrosynthetically at the amide bond to reveal the acid portion 2 and the amine fragment 3. The synthesis of key intermediate 2 is highlighted by a ZnCl(2)-MAEP complex 19 catalyzed diastereoselective Michael reaction of dioxolane 7 with 2-cyclopenten-1-one (5) to establish the contiguous quaternary-tertiary chiral centers and a subsequent geminal difluorination of ketone 17 using Deoxofluor in the presence of catalytic BF(3).OEt(2). The synthesis of the amine moiety 3 is highlighted by the discovery of a novel n-Bu(3)MgLi magnesium-halogen exchange reaction for selective functionalization of 2,6-dibromopyridine. This new and practical metalation protocol obviated cryogenic conditions and upon quenching with DMF gave 6-bromo-2-formylpyridine (26) in excellent yield. Further transformations afforded the amine fragment 3 via reductive amination with 35, Pd-catalyzed aromatic amination, and deprotection. Finally, the highly convergent synthesis of 1 was accomplished by coupling of the two fragments. This synthesis has been used to prepare multi-kilogram quantities of the bulk drug.

Published
2001

2. Ni-catalyzed nucleophilic conjugate additions of Grignard and organozincate reagents to substituted 4-vinylpyridines. General synthesis of phosphodiesterase IV inhibitors

Author

Jaemoon Lee, Audrey Molina, Bob Reamer, Ioannis N. Houpis, Paul J. Reider, Ralph P. Volante, and Ilias Dorziotis

Subjects
chemistry.chemical_classification, Olefin fiber, Aryl, Organic Chemistry, Biochemistry, Medicinal chemistry, Catalysis, chemistry.chemical_compound, chemistry, Nucleophile, Yield (chemistry), Reagent, Drug Discovery, Organic chemistry, Alkyl, Conjugate
Abstract

Alkyl, aryl, and vinyl Grignard reagents were added to olefin II under Ni(acac) 2 or Cl 2 Ni(PPh 3 ) 2 catalysis to give products with the general formula I in 74–95% yield. Organozincates gave similar results with Ni(acac) 2 as the catalyst.

Published
1998

3. Nickel catalyzed addition of organozincates to optically pure vinylic sulfoxides. Synthesis of the phosphodiesterase IV inhibitor L-765,527 (CDP-840)

Author

Robert A. Reamer, Ilias Dorziotis, Ralph P. Volante, Paul J. Reider, Ioannis N. Houpis, and Audrey Molina

Subjects
Organic Chemistry, chemistry.chemical_element, Sulfoxide, Biochemistry, Catalysis, Flue-gas desulfurization, Phosphodiesterase IV, chemistry.chemical_compound, Nickel, chemistry, Yield (chemistry), Drug Discovery, Organic chemistry, Enantiomeric excess
Abstract

Ph3ZnMgCl was added to the optically pure sulfoxide 3 in the presence of Ni(acac)2 to give, after desulfurization, the phosphodiesterase IV inhibitor 1 in good yield and 92% enantiomeric excess.

Published
1997

4. ChemInform Abstract: Nickel-Catalyzed Addition of Organozincates to Optically Pure Vinylic Sulfoxides. Synthesis of the Phosphodiesterase IV Inhibitor L-765,527 (CDP-840)

Author

Robert A. Reamer, Ioannis N. Houpis, Paul J. Reider, Ralph P. Volante, Audrey Molina, and Ilias Dorziotis

Subjects
Phosphodiesterase IV, chemistry.chemical_compound, Nickel, chemistry, Yield (chemistry), chemistry.chemical_element, Sulfoxide, General Medicine, Enantiomeric excess, Medicinal chemistry, Catalysis, Flue-gas desulfurization
Abstract

Ph3ZnMgCl was added to the optically pure sulfoxide 3 in the presence of Ni(acac)2 to give, after desulfurization, the phosphodiesterase IV inhibitor 1 in good yield and 92% enantiomeric excess.

Published
2010

5. ChemInform Abstract: Ni-Catalyzed Nucleophilic Conjugate Additions of Grignard and Organozincate Reagents to Substituted 4-Vinylpyridines. General Synthesis of Phosphodiesterase IV Inhibitors

Author

Ralph P. Volante, Bob Reamer, Jaemoon Lee, Ioannis N. Houpis, Ilias Dorziotis, Audrey Molina, and Paul J. Reider

Subjects
chemistry.chemical_classification, chemistry.chemical_compound, Olefin fiber, chemistry, Nucleophile, Aryl, Yield (chemistry), Reagent, General Medicine, Medicinal chemistry, Alkyl, Conjugate, Catalysis
Abstract

Alkyl, aryl, and vinyl Grignard reagents were added to olefin II under Ni(acac) 2 or Cl 2 Ni(PPh 3 ) 2 catalysis to give products with the general formula I in 74–95% yield. Organozincates gave similar results with Ni(acac) 2 as the catalyst.

Published
2010

6. Synthesis of a Muscarinic Receptor Antagonist via a Diastereoselective Michael Reaction, Selective Deoxyfluorination and Aromatic Metal-Halogen Exchange Reaction

Author

Toshiaki Mase, Ioannis N. Houpis, Atsushi Akao, Ilias Dorziotis, Khateeta Emerson, Thoa Hoang, Takehiko Iida, Takahiro Itoh, Keisuke Kamei, Shinji Kato, Masashi Kawasaki, Fengrui Lang, Jaemoon Lee, Joseph Lynch, Peter Maligres, Audrey Molina, Takayuki Nemoto, Shigemitsu Okada, Robert Reamer, Zhiguo J. Song, David Tschaen, Toshihiro Wada, David Zewge, R. P. Volante, Paul J. Reider, and Koji Tomimoto

Subjects
Organic Chemistry
Published
2001

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