Successively, 145 g (0.5 mole) of trimethoprime and 83 g (0.5 mole) of
vanillin was added to 500 ml of pyridine, and about 130 g of sulfurous
anhydride was added in three hours. The temperature of the reaction mixture
rose spontaneously between 40° and 50°C from the start of the introduction
and was held there until the end of the reaction. It was left for 24 hours at
ordinary temperature. Then the reaction mixture was poured into a large
volume of ether, the precipitate which appeared was filtered off and washed
with ether. The crude product was then dispersed in water and treated with
dilute sodium hydroxide to pH 9.30-9.40. A light insoluble substance was
filtered off, then the product was reprecipitated by the addition of hydrochloric
acid to the alkaline solution to pH 2-3. It was filtered, washed with water, and
then with ethanol. After drying, (+/-)-α-[[4-amino-5-[(3,4,5-
trimethoxyphenyl)methyl]-2-pyrimidinyl]amino]-3-ethoxy-4-
hydroxybenzenemethanesulfonic acid, was obtained, melting point 145°C. TLC
of the product gave a single spot.
The sodium salt of the product was obtainable by treatment of the aqueous
suspension of the acid form with dilute sodium hydroxide to a pH of 8.80.
After evaporation of the solution under reduced pressure and drying, the
sodium salt of the desired derivative of melting point 170°C was obtained.
