The usual synthesis of metformin, originally described in 1922 involves the one-pot reaction of dimethylamine hydrochloride and 2-cyanoguanidine over heat [REF].
According to the procedure described in the 1975 Aron patent,[REF] and the Pharmaceutical Manufacturing Encyclopedia,[REF] equimolar amounts of dimethylamine and 2-cyanoguanidine are dissolved in toluene with cooling to make a concentrated solution, and an equimolar amount of hydrogen chloride is slowly added.