Methamizole sodium, 1-phenyl-2,3-dimethyl-4-methylaminopyrazolone-5-N-sodium methansulfonate (3.2.16), is synthesized in a multi-stage synthesis from
acetoacetic ester and phenylhydrazine. Their reaction leads to the formation of 1-phenyl-
3-methylpyrazolone-5 (3.2.9). Methylation of this product with methyl iodide gives 1-phenyl-
2,3-dimethylpyrazolone-5 (3.2.10). This compound is used independently in medicine as a
fever-reducing and anti-inflammatory analgesic under the name antipyrin. It undergoes
nitrozation by sodium nitrite in an acidic medium, forming 1-phenyl-2,3-dimethyl-4-
nitrozopyrazolone-5 (3.2.11). Reduction of the nitrous derivative (3.2.11) by different reducing agents leads to the formation of 1-phenyl-2,3-dimethyl-4-aminopyrazolone-5 (3.2.12).
This product is reacted with benzaldehyde, forming an easily separable crystalline 1-phenyl-
2,3-dimethyl-4-benzylidenaminopyrazolone-5 (3.2.13), which is methylated at the imine atom
of nitrogen by dimethylsulfate, giving a quaternary salt (3.2.14). Hydrolysis of the resulting
salt gives 1-phenyl-2,3-dimethyl-4-methylaminopyrazolone-5 (3.2.15). Treating the product
with a water solution of a mixture of sodium bisulfite and formaldehyde leads to the formation of 1-phenyl-2,3-dimethyl-4-methylaminopyrazolone-5-N-sodium methanesulfonate
(3.2.16), the desired sodium methamizole [72¨C75].
