Safety

Toxicity

LD50 orally in rats: 130 mg/kg (Hendrix)

Hazard and Precautionary Statements (GHS)

5-Ethyl-5-(1-methyl-1-butenyl)-2-sodiooxy-4,6(1H,5H)-pyrimidinedione Chemical Properties,Usage,Production

Originator

Delvinal,MSD,US ,1943

Manufacturing Process

6.9 parts of sodium are dissolved in 100 parts of absolute ethyl alcohol in a vessel provided with a reflux condenser. After the sodium is dissolved, 9.6 parts of urea and 20.9 parts of the ethyl ester of ethyl (1-methyl-δ 1 - butenyl)cyanoacetic acid are added. The mixture is refluxed for twelve hours, after which the alcohol is removed by vacuum distillation and the residue is dissolved in 100 parts of water. The resulting solution is extracted with ether in three successive 25 part portions. The nitrile which is formed as a by- product from the cyanoacetate used is recovered from the ether extract by washing with water, evaporating the ether and distilling. The combined water solutions containing 5-ethyl-5-(1-methyl-δ 1 -butenyl)-4-imino barbituric acid, are acidified until acid to Congo red with concentrated hydrochloric acid, after which the mixture is transferred, if necessary, to another vessel, and an equal volume of concentrated hydrochloric acid is added. The solution is then refluxed for one hour to hydrolyze the imino compound. The 5-ethyl-5-(1- methyl-δ 1 -butenyl)barbituric acid crystallizes out on cooling. It is filtered and washed with two 25 part portions of ice water. By this process, 8 parts of the crude product (35% yield) have been obtained. After two crystallizations from 50% alcohol, the yield of the purified product is 6.5 parts (29%). The product melts at 160°C to 162°C.
The sodium salt of 5-ethyl-5-(1-methyl-δ 1 -butenyl)barbituric acid is prepared by dissolving 23 parts of sodium in 350 parts of absolute alcohol in a vessel provided with a reflux condenser containing a drying tube, and adding the resulting solution to a solution of 224 parts of 5-ethyl-5-(1-methyl-δ 1 - butenyl)barbituric acid dissolved in 300 to 400 parts of absolute alcohol. The resulting solution is concentrated in vacuo, with heating on a warm water bath. About 200 parts of dry benzene are then added and the mixture is again concentrated, If this evaporation is carried out to an extent such that all of the solvent is removed, no further washing is required. If all of the solvent is not removed by evaporation, the residue is washed with dry ether. The resulting sodium salt is then dried in an oven at 90°C and then is dried in vacuo (2 mm) at 78°C. The yield is 97% to 99%.

Therapeutic Function

5-Ethyl-5-(1-methyl-1-butenyl)-2,4,6-(1H,3H,5H)- pyrimidinetrione sodium salt