Replacement of dichloromethane within chromatographic purification : a guide to alternative solvents

Replacement of dichloromethane as the bulk medium within chromatographic purification has been evaluated with a broad range of molecules containing functionality common within Medicinal Chemistry programmes. Analysis of the data set has generated a set of general guidelines to assist in the selection of alternative solvents for CH2Cl2 as the bulk media in these ubiquitously employed processes

Regiospecific synthesis of N2-aryl 1,2,3-triazoles from 2,5-disubstituted tetrazoles via photochemically generated nitrile imine intermediates

The synthesis of N2-aryl 1,2,3-triazoles from 2,5-disubstituted tetrazoles was achieved under photochemical conditions. This simple and mild one-step reaction provides regiospecific access to 2,4,5-substituted 1,2,3-triazoles via a nitrile imine intermediate. Syntheses of alkyl and heterocylic derivatives were also investigated

How does electronic fetal heart rate monitoring affect labor and delivery outcomes?

Continuous electronic fetal monitoring (EFM) reduces the risk of neonatal seizure by 50% compared with intermittent auscultation (IA) (strength of recommendation [SOR]: A, systematic review of randomized controlled trials [RCTs]). EFM increases the incidence of cesarean section by 66% and the incidence of operative vaginal delivery by 16% (SOR: A, systematic review of RCTs). It has no effect on the rates of cerebral palsy or neonatal mortality (SOR: A, systematic review of RCTs). An estimate from a Cochrane meta-analysis suggests that a cohort of 628 women receiving EFM could expect to experience 1 less neonatal seizure and 11 more cesarean sections compared with IA controls

A one-pot Suzuki-hydrogenolysis protocol for the modular synthesis of 2,5-diaryltetrazoles

2,5-Diaryltetrazoles are a diverse range of compounds of considerable interest within the field of photochemistry as a valuable precursor of the nitrile imine 1,3-dipole. Current literature approaches toward this heterocycle remain unsuitable for the practical synthesis of a library of these derivatives. Herein, we disclose the development of a modular approach toward 2,5-diaryltetrazoles compatible with an array-type protocol, facilitated by a tandem Suzuki-hydrogenolysis approach

Positive allosteric modulators of the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor

L-glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) and plays a fundamental role in the control of motor function, cognition and mood. The physiological effects of glutamate are mediated through two functionally distinct receptor families. While activation of metabotropic (G-protein coupled) glutamate receptors results in modulation of neuronal excitability and transmission, the ionotropic glutamate receptors (ligand-gated ion channels) are responsible for mediating the fast synaptic response to extracellular glutamate

Palladium-catalyzed synthesis of aryl amides through silanoate-mediated hydrolysis of nitriles

A procedure for the formation of aryl amides through the palladium-catalyzed coupling of nitriles and aryl bromides, via the formation of intermediary silanoate derived imidate species is reported. Optimization was undertaken and examples of the process are described that furnish the products in up to 86% isolated yield

Transition metal-free coupling of 1,3-dipoles and boronic acids as a sustainable approach to C-C bond formation

The need for alternative, complementary approaches to enable C-C bond formation within organic chemistry is an on-going challenge in the area. Of particular relevance are transformations that proceed in the absence of transition metal reagents. In the current study, we report a comprehensive investigation of the coupling of nitrile imines and aryl boronic acids as an approach towards sustainable C-C bond formation. In situ generation of the highly reactive 1,3-dipole facilitates a Petasis-Mannich-type coupling via a nucleophilic boronate complex. The introduction of hydrazonyl chlorides as a complementary nitrile imine source to the 2,5-tetrazoles previously reported by our laboratory further broadens the scope of the approach. Additionally, we exemplify for the first time the extension of this protocol into another 1,3-dipole, through the synthesis of aryl ketone oximes from aryl boronic acids and nitrile Noxides

Catalytic amidation of unactivated ester derivatives mediated by trifluoroethanol

A catalytic amidation method has been developed, employing 2,2,2-trifluoroethanol to facilitate condensation of unactivated esters and amines, enabling the synthesis of a range of amide products in good to excellent yields. Mechanistic studies indicate the reaction proceeds through a trifluoroethanol-derived active ester intermediate

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

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 crosscoupling and Cacchi-type annulations