The key step in the synthesis of pharmaceutical substance TZ-S is the reaction involving the diazotization of TZ-5 followed by intramolecular cyclisation leading to the creation of tetrazine ring to obtain compound TZ-6:

After a thorough analysis of the literature data regarding the conditions for the reaction of aromatic amines diazotization, the parameters the change may cause increased productivity and/or purity of the resulting product were set (temperature, used acid, equivalent of reagents, solvents etc.).

Using statistical methods area of the reaction response was designated and then series of experiments were performed. Fixed reaction parameters were changed in specific way.

Purity of the resulting product and overall yield of the process was determined by HPLC methods.

The final results determined the optimal conditions for obtaining compound TZ-6.

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