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Ceralasertib is currently being evaluated in multiple phase I/II clinical trials for the treatment of cancer. Its structure, comprising a pyrimidine core decorated with a chiral morpholine, a cyclo...

A three‐step synthesis of the 2‐azabicyclo[3.3.1]nonane ring system from simple pyrroles, employing a combined photochemical/palladium‐catalysed approach is reported. Substrate scope is broad, allowing the incorporation of a wide range of functionality relevant to medicinal chemistry. Mechanistic studies demonstrate that the process occurs by acid‐assisted C−N bond cleavage followed by β‐hydride elimination to form a reactive diene, demonstrating that efficient control of what might be considered off‐cycle reactions can result in productive tandem catalytic processes. This represents a short and versatile route to the biologically important morphan scaffold., Easily diverted: A rapid entry to the biologically important morphan ring system highlights the powerful combination of photochemistry and catalysis. The key palladium‐catalysed transformation utilises a novel diverted Tsuji–Trost sequence. Mechanistic studies demonstrate this process occurs by acid‐assisted C−N bond cleavage followed by β‐hydride elimination to form a reactive diene.

Work to assess the thermal properties of 2-butynoic acid (a precursor to acalabrutinib) has revealed the potential for thermal runaway on heating; testing using accelerated rate calorimetry (ARC) showed exothermic onset from 135 °C, precluding short-path distillation as a means of purification. Recrystallization was shown to be effective as an alternative technique to purify the compound and avoid the distillation procedure.

Tetrahydroisoquinolines and tetrahydrobenzazepines were prepared by acid-promoted ring contraction of cyclic ureas, which were themselves formed by ring expansion of indolines and tetrahydroquinolines. The consequent overall one-carbon insertion reaction gives these 6- and 7-membered heterocyclic scaffolds in three steps from readily available precursors. Other ring sizes may be formed by an alternative elimination reaction of bicyclic structures. Scalability of the method was demonstrated by operating it in a flow system.

AGU fall 2010 - all about heat flow partitioning and planform for different distributions of continental blocks. Official title: Heat Flow Partitioning Between Continents and Oceans - from 2D to 3D