Scheme 2. Overview of Main Processes for Tirapazamine 1 Synthesis.

Reagents and conditions: (a) H₂NCN, neat, 100 °C, yield 80%; (b) H₂O₂ 90% in AcOH, 50 °C, yield 63% or 60–70 °C, yield 28%; (c) guanidine, tBuOK, tetrahydrofuran, 50–60 °C, yield 82%; (d) Na₂NCN, MeOH, H₂O, 50–60 °C, then purification using HOAc, yield 89%