Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Improved Syntheses of the Mglu? Antagonists MMPEP and MTEP Using Sonogashira Cross-Coupling.

ABSTRACT: The Sonogashira cross-coupling, a key step in the syntheses of the mGlu? antagonists MMPEP and MTEP, provided an improved three-step method for the preparation of MMPEP in 62% overall yield. Using Spartan molecular modeling kit an explanation for the failure to employ analogues method in the synthesis of MTEP was sought. The DFT calculations indicated that meaningful isolated yields were obtained when the HOMO energy of the aryl halide was lower than the HOMO energy of the respective alkyne.

SUBMITTER: Mu B

PROVIDER: S-EPMC5874720 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Improved Syntheses of the Mglu₅ Antagonists MMPEP and MTEP Using Sonogashira Cross-Coupling.

Mu Boshuai B Mu Linjing L Schibli Roger R Ametamey Simon M SM Milicevic Sephton Selena S

Pharmaceuticals (Basel, Switzerland) 20180220 1

The Sonogashira cross-coupling, a key step in the syntheses of the mGlu₅ antagonists MMPEP and MTEP, provided an improved three-step method for the preparation of MMPEP in 62% overall yield. Using Spartan molecular modeling kit an explanation for the failure to employ analogues method in the synthesis of MTEP was sought. The DFT calculations indicated that meaningful isolated yields were obtained when the HOMO energy of the aryl halide was lower than the HOMO energy of the respective alkyne. ...[more]

PMID: 29461503

Similar Datasets

Decarbonylative Sonogashira Cross-Coupling of Carboxylic Acids.

Project description:Decarbonylative Sonogashira cross-coupling of carboxylic acids by palladium catalysis is presented. The carboxylic acid is activated in situ by the formation of a mixed anhydride and further decarbonylates using the Pd(OAc)2/Xantphos system to provide an aryl-Pd intermediate, which is intercepted by alkynes to access the traditional Pd(0)/(II) cycle using carboxylic acids as ubiquitous and orthogonal electrophilic cross-coupling partners. The methodology efficiently constructs new C(sp2)-C(sp) bonds and can be applied to the derivatization of pharmaceuticals. Mechanistic studies give support to decarbonylation preceding transmetalation in this process.

| S-EPMC9069321 | biostudies-literature

Alkynylation of graphene via the Sonogashira C-C cross-coupling reaction on fluorographene.

Project description:We report successful grafting of alkynyl groups onto graphene via the Sonogashira reaction between fluorographene and terminal alkynes. Theoretical calculations revealed that fluorographene can efficiently bind and oxidize the palladium catalyst on electrophilic sites activated by fluorine atoms. This paves the way towards conductive and mechanically robust 3D covalent networks.

| S-EPMC6350624 | biostudies-literature

Electronic Coupling in π-Conjugated Molecule-Bridged Silicon Quantum Dot Clusters Synthesized by Sonogashira Cross-Coupling Reaction.

Project description:π-Conjugated molecule-bridged silicon quantum dot (Si QD) clusters were first synthesized by Sonogashira cross-coupling reaction between 4-ethynylstyryl and octyl co-capped Si QDs (4-Es/Oct Si QDs) and 2,5-dibromo-3-hexylthiophene. The formation of Si QD clusters was confirmed by field emission transmission electron microscopy. The electronic coupling between the QDs in the Si QD cluster is significantly enhanced as compared with that for 4-Es/Oct Si QDs, which is verified from the red shift in ultraviolet-visible absorption and photoluminescence spectra of the Si QD cluster with the possibility of exciton transport, the increased charging effect found in the core-level photoemission spectra, the shift to lower binding energy of the valence band photoemission spectrum, and more decisively, the increase in electrical conductance of the Si QD cluster thin film. To investigate the physical origin of the temperature dependence of the electrical conductance, we have merged the microscopic viewpoint, Marcus theory, on the electron transfer (W) between the adjacent QDs, with macroscopic concepts, such as the conductance (G), mobility (μ), and diffusion coefficient (D). The effective reorganizational energies of charge transfer between the neighboring Si QDs in 4-Es/Oct Si QD and Si QD cluster thin films are estimated to be 170 and 140 meV, respectively, while the ratio of the effective electronic coupling of the latter to that of the former is determined to be 7.3:1.

| S-EPMC6648244 | biostudies-literature

Syntheses of ?-pyrones using gold-catalyzed coupling reactions.

Project description:Sequential alkyne activation of terminal alkynes and propiolic acids by gold(I) catalysts yields compounds having ?-pyrone skeletons. Novel cascade reactions involving propiolic acids are reported that give rise to ?-pyrones with different substitution patterns.

| S-EPMC3103191 | biostudies-literature

Palladium Catalyst Recycling for Heck-Cassar-Sonogashira Cross-Coupling Reactions in Green Solvent/Base Blend.

Project description:The identification of a green, versatile, user-friendly, and efficient methodology is necessary to facilitate the use of Heck-Cassar-Sonogashira (HCS) cross-coupling reaction in drug discovery and industrial production in the pharmaceutical segment. The Heck-Cassar and Sonogashira protocols, using N-hydroxyethylpyrrolidone (HEP)/water/N,N,N',N'-tetramethyl guanidine (TMG) as green solvent/base mixture and sulfonated phosphine ligands, allowed to recycle the catalyst, always guaranteeing high yields and fast conversion under mild conditions, with aryl iodides, bromides, and triflates. No catalyst leakage or metal contamination of the final product were observed during the HCS recycling. To our knowledge, a turnover number (TON) up to 2375, a turnover frequency (TOF) of 158 h-1 , and a process mass intensity (PMI) around 7 that decreased around 3 after solvent, base, and palladium recovery, represent one of the best results to date using a sustainable protocol. The Heck-Cassar protocol using sSPhos was successfully applied to the telescoped synthesis of Erlotinib (TON: 1380; TOF: 46 h-1 ).

| S-EPMC8251985 | biostudies-literature

One-Pot Iridium Catalyzed C-H Borylation/Sonogashira Cross-Coupling: Access to Borylated Aryl Alkynes.

Project description:Borylated aryl alkynes have been synthesized via one-pot iridium catalyzed C-H borylation (CHB)/Sonogashira cross-coupling of aryl bromides. Direct borylation of aryl alkynes encountered problems related to the reactivity of the alkyne under CHB conditions. However, tolerance of aryl bromides to CHB made possible a subsequent Sonogashira cross-coupling to access the desired borylated aryl alkynes.

| S-EPMC7181282 | biostudies-literature

Aminophosphine Palladium Pincer-Catalyzed Carbonylative Sonogashira and Suzuki-Miyaura Cross-Coupling with High Catalytic Turnovers.

Project description:This work documents the first palladium pincer complex-catalyzed carbonylative Sonogashira (CS) and carbonylative Suzuki-Miyaura (CSM) cross-coupling. Compared to previous protocols, which employ hazardous and toxic solvents, the aminophosphine pincer complex {[C6H3-2,6-(NHP{piperidinyl}2)2]Pd(Cl)} (III) catalyzes both the cross-coupling reactions in propylene carbonate, an eco-friendly and sustainable polar aprotic solvent. Advantageously, employing III allows the CS cross-coupling to be carried out at a palladium loading of 10-4 mol % and the CSM cross-coupling to be carried out at 10-6 mol %, thus resulting in catalytic turnovers of 105 and 107, respectively. Relative comparison of the pincer complex with conventional palladium precursors Pd(OAc)2 and PdCl2(PPh3)2 shows the efficiency and robustness of the pincer complex in effecting higher catalytic activity at low palladium loadings.

| S-EPMC6648871 | biostudies-literature

Scope and limitations of a DMF bio-alternative within Sonogashira cross-coupling and Cacchi-type annulation.

Project description:Pd-catalysed C-C bond formation is an essential tool within the pharmaceutical and agrochemical industries. Many of these reactions rely heavily on polar aprotic solvents; however, despite their utility, these solvents are incompatible with the drive towards more sustainable chemical synthesis. Herein, we describe the scope and limitations of an alternative to DMF derived from renewable sources (CyreneTM) in Sonogashira cross-coupling and Cacchi-type annulations.

| S-EPMC5082449 | biostudies-literature

Copper-Catalyzed Aza-Sonogashira Cross-Coupling To Form Ynimines: Development and Application to the Synthesis of Heterocycles.

Project description:Nitrogen-substituted alkynes, such as ynamines and ynamides, are versatile synthetic building blocks. Ynimines bearing additional nucleophilic and electrophilic centers relative to ynamines and ynamides are expected to have high synthetic potential. However, their chemical reactivity remains unexplored owing mainly to the lack of synthetic accessibility. We report herein a versatile copper-catalyzed synthesis of ynimines from readily available O-acetyl ketoximes and terminal alkynes. A wide range of O-acetyl ketoximes derived from diaryl ketones, aryl alkyl ketones and dialkyl ketones underwent cross-coupling with a diverse set of terminal alkynes to afford the ynimines in good to excellent yields. An unprecedented [5+1] heteroannulation reaction exploiting the reactivity of the ynimine generated in situ was subsequently developed for the synthesis of medicinally important heterocycles, including isoquinolines, azaindoles, azabenzofurans, azabenzothiophenes and carbolines.

| S-EPMC8596870 | biostudies-literature

Crystal structures of three 4-substituted-2,2'-bipyridines synthesized by Sonogashira and Suzuki-Miyaura cross-coupling reactions.

Project description:Facile synthetic routes for three 4-substituted 2,2'-bi-pyridine derivatives, 4-[2-(4-methyl-phenyl)-ethyn-yl]-2,2'-bi-pyridine, C19H14N2, (I), 4-[2-(pyridin-3-yl)ethyn-yl]-2,2'-bi-pyridine, C17H11N3, (II), and 4-(indol-4-yl)-2,2'-bi-pyridine, C18H13N3, (III), via Sonogashira and Suzuki-Miyaura cross-coupling reactions, respect-ively, are described. As indicated by X-ray analysis, the 2,2'-bi-pyridine core, the ethyl-ene linkage and the substituents of (I) and (II) are almost planar [dihedral angles between the two ring systems: 8.98 (5) and 9.90 (6)° for the two mol-ecules of (I) in the asymmetric unit and 2.66 (14)° for (II)], allowing π-conjugation. On the contrary, in (III), the indole substituent ring is rotated significantly out of the bi-pyridine plane [dihedral angle = 55.82 (3)°], due to steric hindrance. The crystal packings of (I) and (II) are dominated by π-π inter-actions, resulting in layers of mol-ecules parallel to (30-2) in (I) and columns of mol-ecules along the a axis in (II). The packing of (III) exhibits zigzag chains of mol-ecules along the c axis inter-acting through N-H⋯N hydrogen bonds and π-π inter-actions. The contributions of unknown disordered solvent mol-ecules to the diffraction intensities in (II) were removed with the SQUEEZE [Spek (2015 ▸). Acta Cryst. C71, 9-18] algorithm of PLATON. The given chemical formula and other crystal data do not take into account these solvent mol-ecules.

| S-EPMC5382633 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data