Two Cycles with One Catch: Hydrazine in Ugi 4‑CR and Its Postcyclizations

Isocyanide-based multicomponent reactions (IMCR) are by far the most versatile reactions that can construct relatively complex molecules by one-pot synthesis. More importantly, the development of post IMCR modifications significantly improves the scaffold’s diversity. Here, we describe the use of <i>N</i>-Boc protected hydrazine together with α-amino acid derived isocyanides in the Ugi tetrazole reaction and its post cyclization under both acidic and basic conditions. The cyclization in acidic conditions was conducted in a one pot fashion, which give 7-aminotetrazolopyrazinone (<b>6</b>) and tetrazolotriazepinone (<b>7</b>) cyclic products. The post cyclization under basic condition could selectively afford Boc-protected 7-aminotetrazolopyrazinone (<b>8</b>) products in yield of 38–87%