N-[5-(2-methoxyethoxy)pyrimidin-2-yl]benzenesulfonamide

Redul,Bayer/Schering,W. Germany,1964

Glymidine is used in biological activities to predict human intestinal absorption in drug discovery.

ChEBI: Glymidine is a sulfonamide that is N-(pyrimidin-2-yl)benzenesulfonamide which is substituted at position 5 of the pyrimidine ring by a 2-methoxyethoxy group. It is a hypoglycemic drug used for the treatment of diabetes mellitus. It has a role as a hypoglycemic agent. It is a member of pyrimidines, a sulfonamide and a diether. It is a conjugate acid of a glymidine(1-).

210 g phosphorus pentachloride are gradually added to 252 g methoxyethoxyacetaldehyde-di-methoxyethylacetal with agitation. The mixture is externally cooled with ice to hold the reaction temperature below 25°C. Moisture is carefully excluded. After addition of the condensation agent is completed, the reaction mixture is further agitated at room temperature for 30 minutes. 225 ml dimethylformamide are then added drop by drop while the reaction temperature is held at 20°C to 25°C by external cooling of the reaction vessel with ice. When the dimethylformamide has been added, the temperature is raised to 60°C, and this temperature is maintained for 70 minutes.
The temperature is again lowered to 20°C to 25°C and maintained at this value by cooling with ice while 500 ml methanol are added drop by drop. The resulting solution is admixed drop by drop to a suspension of 240 g powdered caustic soda in 800 ml methanol at 20°C to 25°C. After mixing is completed, stirring is continued for 30 minutes at room temperature. The solution now contains inorganic salts and β-dimethylamino-α-methoxyethoxyacrolein.
200 g guanidine nitrate and thereafter 70 g sodium hydroxide are added to the solution. The methanol is evaporated with agitation. The residue is dissolved in 1.5 liters water and is repeatedly extracted with chloroform. The combined chloroform extracts are evaporated to dryness, and the residue is recrystallized from carbon tetrachloride. 80 g of 2-amino-5- methoxyethoxypyrimidine of MP 80°C to 81°C are obtained.
This material is then dissolved in pyridine. Benzenesulfonylchloride is added and the resulting mixture is heated two hours to 60°C. It is then poured into 300 ml water. The precipitate formed thereby is filtered off and dissolved in dilute ammonium hydroxide. The solution is purified with charcoal, and filtered. The filtrate is acidifed with acetic acid to give glymidine.
62 g 2-benzenesulfonamido-5-methoxyethoxypyrimidine are dissolved jointly with 8 g sodium hydroxide in 250 ml ethanol. The solution is evaporated to dryness, and the residue is suspended in 300 ml acetone. The sodium salt of 2-benzenesulfonamido-5-methoxyethoxypyrimidine may be filtered off, washed with acetone, and dried. The yield of glymidine sodium is about 60 g, the MP 220°C to 223°C.

Antidiabetic