Over the past several years GSK has been developing the capability to perform continuous hydrogenations within trickle bed reactors. Motivation to develop this technology stems from the ability of trickle bed reactors to perform hydrogenations at high pressures (up to 100 bar within GSK), which is considerably greater than our current hydrogenation batch vessels (5 bar). This allows access to chemistry with improved quality and productivity, with the added benefit of enhanced process control, reduced reactor size, reduced vessel cleaning time, greener processes, and increased safety. To support this ambition a new generation of catalysts for pharmaceutical-scale continuous hydrogenations have been developed with traditional and nontraditional catalyst suppliers. Herein we discuss a procedure to characterize and assess the suitability of the new catalysts from a nontraditional supplier for use in laboratory and pilot plant scale reactors (reactor volume 0.1 to 0.5 L).

A methodology for the synthesis of α‐ and β‐carbolines from fluoropyridines and 2‐haloanilines is reported. This procedure consists of a four‐step directed ortho‐lithiation, zincation, Negishi cross‐coupling, and intramolecular nucleophilic aromatic substitution, providing access to a diverse set of functionalized carbolines. While the procedure is applicable to batch conditions, the generation of arylzinc intermediates in continuous flow has been demonstrated.

Carbolines are privileged scaffolds in medicinal chemistry, and therefore, novel and efficient approaches to their synthesis are in high demand. An efficient method for the synthesis of α- and β-carbolines from fluoropyridines and 2-haloanilines is reported. This streamlined procedure consists of a four-step directed ortho-lithiation, zincation, Negishi cross-coupling, and intramolecular nucleophilic aromatic substitution, providing access to a diverse set of functionalised carbolines. While the procedure is applicable to batch conditions, the generation of arylzinc intermediates in continuous flow has been demonstrated .

Carbolines are considered to be privileged scaffolds in medicinal chemistry. An efficient method for the synthesis of α- and β-carbolines from fluoropyridines and 2-haloanilines is reported. This streamlined procedure consists of a four-step directed ortho-lithiation, zincation, Negishi cross-coupling, and intramolecular nucleophilic aromatic substitution, providing access to a diverse set of functionalized carbolines. While the procedure is applicable to batch conditions, the generation of arylzinc intermediates in continuous flow has been demonstrated.

Carbolines are considered to be privileged scaffolds in medicinal chemistry. An efficient method for the synthesis of α- and β-carbolines from fluoropyridines and 2-haloanilines is reported. This streamlined procedure consists of a four-step directed ortho-lithiation, zincation, Negishi cross-coupling, and intramolecular nucleophilic aromatic substitution, providing access to a diverse set of functionalized carbolines. While the procedure is applicable to batch conditions, the generation of arylzinc intermediates in continuous flow has been demonstrated.