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

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.