Synthesis and biological evaluation of novel 2,3-dihydro-1H-1,5-benzodiazepin-2-ones; potential imaging agents of the metabotropic glutamate 2 receptor

A focused library of novel 2,3-dihydro-1H-1,5-benzodiazepin-2-ones containing sites for 11C-, 18F- and 123I-labelling have been prepared and evaluated against membrane expressing human recombinant metabotropic glutamate 2 receptor (mGluR2). The compounds were found to be non-competitive antagonists with nanomolar affinity. HPLC evaluation of the physiochemical properties of these compounds identified two candidates for PET and SPECT imaging of mGluR2

Activation of Pyridinium Salts for Electrophilic Acylation: a Method for Conversion of Pyridines into 3-Acylpyridines

Cyanide adducts of N-MOM pyridinium salts react with strong acylating reagents to provide 3-acyl-4-cyano-1,4-dihydropyridines that can be aromatized to 3-acylpyridines using ZnCl 2 in refluxing ethanol.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41517/1/10593_2004_Article_496956.pd

3,5-Bis(trifluoromethyl)iodobenzene

InChI = 1S/C8H3F6I/c9-7(10,11)4-1-5(8(12,13)14)3-6(15)2-4/h1-3H InChIKey = VDPIZIZDKPFXLI-UHFFFAOYSA-N (reagent used as a versatile allylation or arylation component) Physical Data: bp 59–61 °C (10 mmHg); fp 74 °C; d 1.919 g cm^(−3). Solubility: sol DMF, acetonitrile, toluene, and most organic solvents. Form Supplied in: pale pink liquid; commercially available. Purification: dried over MgSO_4 and fractionally distilled under vacuum. Handling, Storage, and Precautions: air, light, and moisture sensitive; to be handled in an inert atmosphere; stored in cool, dark, and dry conditions and away from oxidizing agents

Catalyst-Controlled Chemoselective Arylation of 2-Aminobenzimidazoles

What N would you like? The chemoselective and complementary Pd- and Cu-catalyzed N-arylation of 2-aminobenzimidazoles is described. Selective N-arylation of the amino group was achieved with a Pd-catalyzed method, while selective N-arylation of azole nitrogen was achieved with a Cu-catalyzed procedure (see scheme).National Institutes of Health (U.S.) (GM58160

Origins of High Catalyst Loading in Copper(I)-Catalysed Ullmann- Goldberg C-N Coupling Reactions

Mechanistic investigation of Ullmann-Golberg reactions using soluble and partially soluble bases led to identification of various pathways for catalyst deactivation through (i) product inhibition with amine products, (ii) byproduct inhibition with inorganic halide salts, and (iii) ligand exchange by soluble carboxylate bases. Reactions using a partially soluble inorganic bases showed variable induction periods, which is responsible for reproducibility issues in these reactons. Surprisingly, more finely milled Cs2CO3 resulted in longer induction period due to higher concentration of deprotonated amine/amide, leading to suppressed catalytic activity. These results have singificant implications on future ligand development for Ullmann-Goldberg reaction, and on the solid form of the inorganic bases as an important variable with mechanistic ramifications in many catalytic reactions

Origins of High Catalyst Loading in Copper(I)-Catalysed Ullmann- Goldberg C-N Coupling Reactions

Mechanistic investigation of Ullmann-Golberg reactions using soluble and partially soluble bases led to identification of various pathways for catalyst deactivation through (i) product inhibition with amine products, (ii) byproduct inhibition with inorganic halide salts, and (iii) ligand exchange by soluble carboxylate bases. Reactions using a partially soluble inorganic bases showed variable induction periods, which is responsible for reproducibility issues in these reactons. Surprisingly, more finely milled Cs2CO3 resulted in longer induction period due to higher concentration of deprotonated amine/amide, leading to suppressed catalytic activity. These results have singificant implications on future ligand development for Ullmann-Goldberg reaction, and on the solid form of the inorganic bases as an important variable with mechanistic ramifications in many catalytic reactions

A conceptual framework for analysing and planning synthetic approaches to diverse lead-like scaffolds.

Historically, chemists' exploration of chemical space has been exceptionally uneven and unsystematic. This feature article outlines a comprehensive conceptual framework that may be used to capture, analyse and plan synthetic approaches that may address this historically uneven exploration. Illustrative examples of synthetic approaches that target, or have potential to target, broad tracts of lead-like chemical space are presented within the context of this conceptual framework. Particular emphasis is placed on synthetic approaches that enable the combinatorial variation of molecular scaffold, particularly within the boundaries of lead-like chemical space