Patent GB-666027-A (GB)
Title: New pyrimidine derivatives
IPC: A47C/
Filed: 1949-07-27
Abstract: The invention comprises pyrimidine derivatives possessing anticonvulsant properties and of the general formula <FORM:0666027/IV (b)/1> (wherein R1 represents a monocyclic carbocyclic radical or an alkenyl radical of not more than 3 carbon atoms, R2 represents an alkyl radical or an alkenyl radical of not more than 3 carbon atoms, and R3 represents hydrogen or an alkyl radical of not more than 4 carbon atoms), and their manufacture by reduction (e.g. with hydrogen, either electrolytically or in the presence of a hydrogenation catalyst) of a compound of the formula <FORM:0666027/IV (b)/2> (wherein X represents oxygen or sulphur and Y represents hydrogen or, when X is sulphur, may represent an alkyl radical), or by condensation of a malondiamide derivative of the formula <FORM:0666027/IV (b)/3> with formamide (e.g. by heating the reactants together).  In examples: (1) 5-phenyl-5-ethyl-2-thiobarbituric acid is reduced with Raney nickel in alcohol to 5-phenyl-5-ethylhexahydropyrimidine-4:6-dione; (2) the same product is obtained by refluxing a -phenyl-a -ethylmalondiamide with formamide; (3) 2-methylthio-5-phenyl - 5 - ethyltetrahydropyrimidine - 4:6 - dione is reduced as in (1); (4) 5-phenyl-5-ethylbarbituric acid is reduced electrolytically; (5) the malondiamide in (2) is replaced by the appropriate starting materials to yield 5-phenyl-5-methyl-, -n-propyl- and -allyl- and 5-cyclohexyl - 5 - n - propyl - hexahydropyrimidine - 4:6-dione; (6) the appropriate 5-disubstituted-2-thiobarbituric acids are reduced as in (1) to 5 - phenyl - 5 - isopropyl - and 5 - cyclohexyl - 5-ethyl- and -n-propyl-hexahydropyrimidine-4:6-diones; (7) the malondiamide in (2) is replaced by the appropriate a :a :N-trisubstituted malondiamides to produce 5-phenyl-1:5-diethyl- and -dimethyl-, 5-phenyl-5-methyl-1-n-propyl-, 5-phenyl-5-ethyl-1-methyl- and -n-propyl- and 5-phenyl-5-n-propyl-1-methylhexahydropyrimidine-4:6-dione; (8) a : a -diallylmalondiamide similarly gives 5:5-diallylhexahydropyrimidine-4:6-dione.  2 - Methylthio - 5 - phenyl - 5 - ethyltetrahydro pyrimidine-4:6-dione is obtainable by treating 5 - phenyl - 5 - ethyl - 2 - thiobarbituric acid with methyl iodide in aqueous alcoholic sodium hydroxide.  5 - Phenyl - 5 - methyl- and - isopropyl- and 5 - cyclohexyl - 5 - ethyl - and - n - propyl - 2 - thiobarbituric acids are obtainable by condensing the appropriately substituted malonic esters with thiourea.  a  - Phenyl - a  - n - propyl, - isopropyl - and -allyl- and a -cyclohexyl-a -n-propyl-malondiamides are obtainable by hydrolysing the corresponding malonic esters with aqueous alcoholic sodium hydroxide, treating the free acids with phosphorus pentachloride, and reacting the resulting malonyl chlorides with aqueous ammonia.  a  - Phenyl - a  - methyl - N - methyl - and - n - propyl -, a  - phenyl - a  - ethyl - N - methyl -, -ethyl- and -n-propyl- and a -phenyl-a -n-propyl-N-methyl-malondiamides are obtainable from the corresponding a :a -disubstituted ethyl cyanacetates by the action of aqueous alcoholic amines to a :a -phenylalkyl-N-alkylcyanacetamides, followed by hydrolysis with cold concentrated sulphuric acid.