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Updated: Aug 8, 2025

Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines
Published on: June 23, 2019
Verification of preparations of (1H-indol-3-yl)methyl electrophiles and development of their microflow rapid
Hisashi Masui1, Sena Kanda2, Shinichiro Fuse3
1Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan. masui@ps.nagoya-u.ac.jp.
Abstract:
Although highly reactive (1H-indol-3-yl)methyl electrophiles such as (1H-indol-3-yl)methyl halides are potential precursors for the synthesis of various indole derivatives, some researchers have reported difficulties in their preparation due to concomitant undesired dimerization/oligomerization. Nevertheless, there have been some reports on the preparation of (1H-indol-3-yl)methyl halides. To resolve this contradiction, all the previously reported preparations of (1H-indol-3-yl)methyl halides were examined. However, we could not reproduce any of these preparations, and we revised several structures of indole derivatives. Here we show the rapid (0.02 s) and mild (25 °C) generation of an (1H-indol-3-yl)methyl electrophile that enables the rapid (0.1 s) and mild (25 °C) nucleophilic substitution in a microflow reactor. Eighteen unprotected indole analogues can be successfully synthesized using the developed microflow nucleophilic substitution with various nucleophiles.
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