The development of a continuous manufacturing process for a hydrazine condensation reaction at high temperature is reported. This continuous process represents a safer approach to manufacture 3-phenyl-1H-pyrazol-5-amine at scale and exhibits better impurity control compared to a traditional batch process. A controlled crystallization allowed consistently low levels of residual hydrazine (<20 ppm) in isolated solids for further processing to final drug substance. The scalability and robustness of the continuous process was demonstrated at 3 kg scale with a throughput of 0.5 kg/h.

• Shanghai SynTheAll Pharmaceutical Company Limited (“STA”)
• Agios Pharmaceuticals, Inc.

• Intermediate

1. crystallization
2. hydrazine
3. Intermediate
4. pyrazole-5-amine
5. Research Article
6. Scale-up