The Groebke-Blackburn-Bienayme Reaction

Imidazo[1,2a]pyridine is a well‐known scaffold in many marketed drugs, such as Zolpidem, Minodronic acid, Miroprofen and DS‐1 and it also serves as a broadly applied pharmacophore in drug discovery. The scaffold revoked a wave of interest when Groebke, Blackburn and Bienaymé reported independently a new three component reaction resulting in compounds with the imidazo[1,2‐a]‐heterocycles as a core structure. During the course of two decades the Groebke Blackburn Bienaymé (GBB‐3CR) reaction has emerged as a very important multicomponent reaction (MCR), resulting in over a hundred patents and a great number of publications in various fields of interest. Now two compounds derived from GBB‐3CR chemistry received FDA approval. To celebrate the first 20 years of GBB‐chemistry , we present an overview of the chemistry of the GBB‐3CR, including an analysis of each of the three starting material classes, solvents and catalysts. Additionally, a list of patents and their applications and a more in‐depth summary of the biological targets that were addressed, including structural biology analysis, is given

Novel Protocols for the Synthesis of Imidazopyridines, Quinolines and Fused Indazoles via Cycloaddition and C-H Activation Strategies

Heterocycles are an important class of compounds, not only due to their natural abundance, but also because of their chemical and biological significance. Natural product scaffolds have been well recognized as “privileged heterocyclic structures” in terms of their ability to be the basis for successful drugs. An assessment of all FDA approved new molecular entities (NMEs) reveals that natural products and their derivatives represent over one-third of all NMEs. Such scaffolds can be used as cores of compound libraries. In this context, the design of amenable synthetic approaches for the synthesis of new heterocyclic systems is an attractive and challenging area. Cycloadditions have emerged as the most efficient chemical processes, combining atom economy, stereospecificity, and the ability to generate molecular complexity in a single step. Hence they have become increasingly popular among synthetic chemists, and a very large fraction of complex (natural) products syntheses include cycloadditions, often as the key step. Among the cycloaddition reactions, Diels–Alder reaction, with its rich synthetic diversity, is recognized as a powerful tool for regio-, stereoselective preparation of natural and unnatural polycarbocycles and polyheterocycles. [4+1] cycloaddition is among most powerful reactions in the arsenal of the synthetic chemists and counts next to the well-known [3+2] cycloaddition reaction for the synthesis of five-membered rings owing to the ubiquity of five-membered carbo- and heterocyclic substructures in natural products. Construction of C-C and C-X via C-H bond activation/functionalization has attracted great attention in the past decades. However, selective C-H activation has been a challenging task, owing to the ubiquitous nature of C-H bond in organic molecules. In this aspect, along with transition-metal catalysed C-H functionalization, recently alternative, metal-free versions have become very important due to economic and environmental concerns. A highly atom economic, efficient and yet environmentally friendly method has been the prime synthetic target to be achieved by the chemists for synthesizing complex heterocycles, since last few decades. In this context, sequential one-pot multicomponent reactions have been widely explored. Inspired by these, we have developed novel protocols for the synthesis of imidazopyridines, 4-aminoquinolines, isocryptolepine alkaloid analogs and fused indazoles via cycloaddition and C-H activation strategies

Micellar properties of benzyldimethyldodecylammonium bromide in aquo-organic solvent media

1230-1233The micellar properties of benzyldimethyldodecyl-ammonium bromide has been studied by conductivity method in the binary mixtures (10% v/v) of acetonitrile, dimethyl sulfoxide, tetrahydrofuran,1,4-dioxane, methanol and ethylene glycol at different temperatures ranging from 300 to 319 K. The thermodynamics of micellization i.e, Gibbs free energy (ΔGºm), enthalpy (ΔHºm), and entropy (ΔSºm) have also been determined. The increase of critical micelle concentration with solvent mixtures has been discussed on the basis of water structure, solvent properties and hydrophobic interaction

Microwave-assisted facile synthesis of [a]-annelated pyrazolopyrroloindoles via intramolecular azomethine imine 1,3-dipolar cycloaddition

The synthesis of [a]-annelated pyrazolopyrroloindoles via intramolecular 1,3-dipolar cycloaddition of in situ generated azomethine imine from N-allylated indole-2-carboxaldehyde, in regio- and stereoselective manner by using microwave irradiation is described. A one-pot strategy for the expedient synthesis of pyrazolopyrroloindoles has been develope

Continuous-Flow Visible Light Organophotocatalysis for Direct Arylation of 2H-Indazoles: Fast Access to Drug Molecules

A continuous-flow homogeneous photocatalytic method has been devised for the direct arylation of 2H-indazoles. This visible-light-promoted approach directly accesses a wide range of structurally diverse C3-arylated scaffolds of biological interest in a fast (1 min), single-step reaction by using eosin Y as an organophotocatalyst. Furthermore, a microreactor technology is also employed for the fast synthesis of liver X receptor inhibitor drugs with very good yields under metal-free conditions, whereas the reported methods required multiple steps and much longer reaction times (18-24 h).11Nscopu

Metal-Free Regioselective Dual C-H Functionalization in a Cascade Fashion: Access to Isocryptolepine Alkaloid Analogues

A metal-free regioselective approach to annulated indazoles is presented via dual C-H functionalization of indazole and benzylamine in a cascade fashion. The salient features of the present protocol are regioselective C3-functionalization, one-pot synthesis of annulated scaffolds, metal-free, peroxide-free, operationally simple and wide substrate scope