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Efficient Synthesis of 1,4-Diaryl-5-methyl-1,2,3-triazole, A Potential mGluR1 Antagonist, and the Risk Assessment Study of Arylazides

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posted on 20.11.2009 by Takayuki Tsuritani, Hiroo Mizuno, Nobuaki Nonoyama, Satoshi Kii, Atsushi Akao, Kimihiko Sato, Nobuyoshi Yasuda, Toshiaki Mase
A concise and practical synthesis of a 1,4-diaryl-5-methyl-1,2,3-triazole is described. A mGluR1 antagonist 1 was prepared with one-pot operation by the Negishi coupling reaction between two building blocks, 5-bromophthalimidine (2) and 1-aryl-5-methyl-4-triazolylzinc (3-Zn). Bromide 2 was synthesized via N-selective cyclization of o-hydroxymethylbenzamide 8 easily prepared from phthalide 4. Zinc species 3-Zn was generated in situ by transmetalation of 1-aryl-4-magnesio-5-methyltriazole (3-Mg), which in turn was generated by the regioselective click chemistry between 2,4-difluorophenylazide (5) and propynylmagnesium bromide. The risk assessment of potentially explosive arylazides is also mentioned.