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

Abstract

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.

• Authors: Wei Hu, Yuanchang Liu, Xiang Zhang, Panpan Zheng, Feifei Yang, Guangyang Guo, Xin Xie, Jiuzhong Huang, Weiming Chen
• Journal: RSC advances (RSC Adv) Vol. 13 Issue 6 Pg. 3688-3693 (Jan 24 2023) ISSN: 2046-2069 [Electronic] England
• PMID: 36756552 (Publication Type: Journal Article)
• Copyright: This journal is © The Royal Society of Chemistry.