Refernces
10.1021/jo016196i
The study presents a novel method for synthesizing 2-chloroquinolines from 2-vinylanilines using diphosgene in acetonitrile as the solvent. The researchers detail a three-step reaction mechanism involving the generation of phenylisocyanate, quinoline ring formation, and chlorination at the C2 position of the quinoline. The purpose of the chemicals used in the study was to facilitate these steps, with diphosgene reacting with 2-vinylanilines to produce phenyl isocyanate, which then reacts with the acetonitrile to form the quinoline ring. The final step involves the chlorination of the C2 position. This new method eliminates the need for the hazardous use of excess phosphorus oxychloride, which was previously required in the synthesis of 2-chloroquinolines from 2(1H)-quinolinones. The study also discusses the role of acetonitrile as a reactive solvent in the process and provides evidence that the third step, chlorination, is likely the rate-determining step in the reaction.
10.1016/j.bmcl.2007.07.081
The research focuses on the development of pyrrolidine-based inhibitors of dipeptidyl peptidase IV (DPP4) for the treatment of type 2 diabetes. The purpose of the study was to optimize the potency, selectivity, and pharmacokinetic properties of these inhibitors, leading to the identification of a pre-clinical candidate for further profiling. The team synthesized a series of 3-amino-4-phenyl pyrrolidine inhibitors, starting from a high throughput screening hit, and through structure-based design and parallel synthesis, they improved the potency and ADME properties of the series. The research concluded with the identification of compound (+)15b as a promising candidate for further pre-clinical profiling due to its favorable pharmacokinetic and pharmacodynamic profile in rats. Key chemicals used in the process included various heterocycles as replacements for the quinolone fragment, 2,4,5-trifluorophenyl-substituted phenyl rings, and a series of aryl substitutions on the pyrimidine ring, among others, to fine-tune the potency and selectivity of the inhibitors. The X-ray crystal structures of the compounds were deposited in the RCSB protein data bank with code 2QJR.
10.1002/chem.200900583
The research aims to develop sustainable and efficient methods for synthesizing 2-quinolones, which are important structural units in many natural products and drugs. The study introduces novel one-pot sequential Heck reduction–cyclization (HRC) reactions catalyzed by a multitask palladium catalyst supported on charcoal. The process involves a Heck cross-coupling of acrylates with diazonium salts, followed by reduction and cyclization steps under mild conditions without the need for additional ligands or bases. The methodology is notable for its simplicity, mild reaction conditions, and high atom economy, as it internally recycles HBF4, a byproduct of the Heck reaction, as a cocatalyst. The study concludes that this approach is highly efficient for synthesizing a variety of 2-quinolones with different substituents and demonstrates the recyclability of the palladium catalyst for other types of reactions, such as hydrogenation and hydrodehalogenation. This work contributes to the field of sustainable chemistry by offering a straightforward and eco-friendly method for the synthesis of valuable heterocyclic compounds.
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