Small change for big improvement in the preparation of the key intermediate N 1, N 3-disubstituted 1,3,5-triazone of ensitrelvir.

In this study, the key intermediate N 1, N 3-disubstituted 1,3,5-triazone of ensitrelvir fumaric acid, approved in Japan for the treatment of SARS-CoV-2 infection under the emergency regulatory approval system, was produced from S-ethylisothiourea hydrobromide and aminomethyl triazole with CDI by four-step telescoped strategy including CDI-activated, condensation, CDI-cyclization, and N 1-alkylation. The strategy with simple conditions and operations had a total yield of 53% on a gram scale. The strategy for synthesizing the key N 1, N 3-disubstituted 1,3,5-triazone intermediate of ensitrelvir might provide a new avenue for further research and development of ensitrelvir analogs.

Small change for big improvement in the preparation of the key intermediate N1, N3-disubstituted 1,3,5-triazone of ensitrelvir† † Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d2ra07844a

In this study, the key intermediate N1, N3-disubstituted 1,3,5-triazone of ensitrelvir fumaric acid, approved in Japan for the treatment of SARS-CoV-2 infection under the emergency regulatory approval system, was produced from S-ethylisothiourea hydrobromide and aminomethyl triazole with CDI by four-step telescoped strategy including CDI-activated, condensation, CDI-cyclization, and N1-alkylation. The strategy with simple conditions and operations had a total yield of 53% on a gram scale. The strategy for synthesizing the key N1, N3-disubstituted 1,3,5-triazone intermediate of ensitrelvir might provide a new avenue for further research and development of ensitrelvir analogs. A four-step telescoped strategy for synthesis of the key intermediate of ensitrelvir, approved in Japan for the treatment of SARS-CoV-2 infection under the emergency regulatory approval system, was developed.

Two-stage one-pot synthetic strategy for the key triazone-triazole intermediate of ensitrelvir (S-217622), an oral clinical candidate for treating COVID-19.

Herein, the preparation of the key triazone-triazole intermediate of ensitrelvir (S-217622) via sequential cyclization and alkylation reaction is described. Firstly, chloromethyl triazole was synthesized through a one-pot tandem process (condensation and cyclization reaction) from commercially available chloroacetamide in a 72% yield. Then, the key triazone-triazole intermediate was obtained in a second one-pot process by N-alkylation with triazone followed by highly selective N 1-methylation with iodomethane in a 54% yield. In addition, two of the main process impurities were synthesized and identified. This novel alternative two-stage one-pot strategy for synthesizing the key triazone-triazole intermediate opens a new avenue for further research and development of ensitrelvir analogs.

BIM-based task and motion planning prototype for robotic assembly of COVID-19 hospitalisation light weight structures.

Fast transmission of COVID-19 led to mass cancelling of events to contain the virus outbreak. Amid lockdown restrictions, a vast number of construction projects came to a halt. Robotic platforms can perform construction projects in an unmanned manner, thus ensuring the essential construction tasks are not suspended during the pandemic. This research developed a BIM-based prototype, including a task planning algorithm and a motion planning algorithm, to assist in the robotic assembly of COVID-19 hospitalisation light weight structures with prefabricated components. The task planning algorithm can determine the assembly sequence and coordinates for various types of prefabricated components. The motion planning algorithm can generate robots' kinematic parameters for performing the assembly of the prefabricated components. Testing of the prototype finds that it has satisfactory performance in terms of 1) the reasonableness of assembly sequence determined, 2) reachability for the assembly coordinates of prefabricated components, and 3) capability to avoid obstacles.