Palladium‐Catalyzed Aromatic Carbon‐Nitrogen Bond Formation

Jiang, Lei; Buchwald, Stephen L.

doi:10.1002/9783527619535.ch13

Cited by 159 publications

(78 citation statements)

References 168 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Compound 28 ( Table 2) was less potent (RORc SRC1 EC 50 > 10 μM) and less metabolically stable (HLM and RLM CL hep = 18, 35 mL/min/kg, respectively) than 29 (RORc SRC1 EC 50 = 82 nM; HLM and RLM CL hep = 13, 33 mL/min/kg, respectively). Compounds 23,25,26,27,29, and 31 were evaluated in a suite of in vitro ADME assays 40 to assess their human and rat plasma-protein binding (PPB), Madin−Darby canine kidney (MDCK) cellular permeability, 41 and aqueous kinetic solubility at pH 7.4 (Table 3). We were encouraged to see that the favorable in vitro ADME profiles of the tertiary sulfonamide compounds exemplified by 31 (Table 3) were maintained in the δ-sultam subseries.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Discovery of 1-{4-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-piperazin-1-yl}-ethanone (GNE-3500): a Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C (RORc or RORγ) Inverse Agonist

Fauber¹,

René²,

Deng³

et al. 2015

J. Med. Chem.

View full text Add to dashboard Cite

Retinoic acid receptor-related orphan receptor C (RORc, RORγ, or NR1F3) is a nuclear receptor that plays a major role in the production of interleukin (IL)-17. Considerable efforts have been directed toward the discovery of selective RORc inverse agonists as potential treatments of inflammatory diseases such as psoriasis and rheumatoid arthritis. Using the previously reported tertiary sulfonamide 1 as a starting point, we engineered structural modifications that significantly improved human and rat metabolic stabilities while maintaining a potent and highly selective RORc inverse agonist profile. The most advanced δ-sultam compound, GNE-3500 (27, 1-{4-[3-fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-piperazin-1-yl}-ethanone), possessed favorable RORc cellular potency with 75-fold selectivity for RORc over other ROR family members and >200-fold selectivity over 25 additional nuclear receptors in a cell assay panel. The favorable potency, selectivity, in vitro ADME properties, in vivo PK, and dose-dependent inhibition of IL-17 in a PK/PD model support the evaluation of 27 in preclinical studies.

show abstract

Section: ■ Results and Discussionmentioning

confidence: 99%

Discovery of 1-{4-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-piperazin-1-yl}-ethanone (GNE-3500): a Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C (RORc or RORγ) Inverse Agonist

Fauber¹,

René²,

Deng³

et al. 2015

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

“…1 Despite the longstanding prevalence of palladium catalysis in this field, much interest has recently been devoted to the use of base-metal catalysis to enable coupling reactions (Figure 1). 2 Our laboratory 3 and others have focused on the use of nickel catalysis due to (a) nickel’s natural abundance and consequential low cost ($720/oz.…”

Section: Introductionmentioning

confidence: 99%

Breaking Amides using Nickel Catalysis

2017

View full text Add to dashboard Cite

Amides have been widely studied for decades, but their synthetic utility has remained limited in reactions that proceed with rupture of the amide C–N bond. Using Ni catalysis, we have found that amides can now be strategically employed in several important transformations: esterification, transamidation, Suzuki–Miyaura couplings, and Negishi couplings. These methodologies provide exciting new tools to build C–heteroatom and C–C bonds using an unconventional reactant (i.e., the amide), which is ideally suited for use in multi-step synthesis. It is expected that the area of amide C–N bond activation using nonprecious metals will continue to flourish and, in turn, will promote the growing use of amides as synthons in organic synthesis.

show abstract

“…Whereas initial efforts to develop transition metal-catalyzed C–N cross-coupling reactions focused on the use of aryl and alkenyl halides as the electrophilic coupling partner (11,12), during the past few years, alkyl halides that are not suitable substrates for classic S N 2 reactions have emerged as useful coupling partners under the combined action of light and copper catalysis (13,14). To date progress has not yet been reported in the development of an asymmetric variant of these reactions, and the use of copper as a photoredox catalyst (15) is uncommon by comparison with precious metals such as iridium and ruthenium.…”

mentioning

confidence: 99%

Asymmetric copper-catalyzed C-N cross-couplings induced by visible light

Kainz

Matier

Bartoszewicz

et al. 2016

Science

644

322

View full text Add to dashboard Cite

Despite a well-developed and growing body of work in copper catalysis, the potential of copper to serve as a photocatalyst remains underexplored. Herein, we describe a photoinduced, copper-catalyzed method for coupling readily available racemic tertiary alkyl chloride electrophiles with amines to generate fully substituted stereocenters with high enantioselectivity. The reaction proceeds at –40 °C under excitation by a blue light-emitting diode and benefits from the use of a single, Earth-abundant transition metal acting as both the photocatalyst and the source of asymmetric induction. An enantioconvergent mechanism transforms the racemic starting material into a single product enantiomer.

show abstract

Palladium‐Catalyzed Aromatic Carbon‐Nitrogen Bond Formation

Cited by 159 publications

References 168 publications

Discovery of 1-{4-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-piperazin-1-yl}-ethanone (GNE-3500): a Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C (RORc or RORγ) Inverse Agonist

Discovery of 1-{4-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-piperazin-1-yl}-ethanone (GNE-3500): a Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C (RORc or RORγ) Inverse Agonist

Breaking Amides using Nickel Catalysis

Asymmetric copper-catalyzed C-N cross-couplings induced by visible light

Contact Info

Product

Resources

About