Patent GB-901749-A (GB)
Title: New 2-substituted pyrimidines
IPC: C07D239/47
Filed: 1958-12-05
Abstract: The invention comprises pyrimidine compounds of the formula <FORM:0901749/IV (b)/1> and their tautomers and salts, wherein R is a mono- or di-alkyl amino group or an alkyleneamino group in which the alkylene chain may be interrupted by nitrogen, oxygen or sulphur atoms and may be substituted by C1-6 alkyl groups, e.g. R1 is halogen, hydroxy, mercapto, amino, C1-6 alkoxy, C1-6 alkyl mercapto, phenylmercapto optionally bearing halo or C1-6 alkyl substituents, mono- or di-lower (i.e. C1-6) aliphatic amino, heterocyclic-C1-6-alkylamino or an alkyleneamino group, in which the alkylene chain may be interrupted by nitrogen, oxygen or sulphur atoms and may be substituted by C1-6 alkyl groups, R2 is a cyano, carbalkoxy, carbamoyl or thiocarbamoyl group and R3 is hydrogen or a C1-6 hydrocarbon radical.  The invention comprises also 2-methylmercapto-4-amino-5-cyano-pyrimidine and its 6-methyl derivative.  The products of the formula I are made by known methods such as (a) converting a substituent in the 2-, 4- or 5-position of a pyrimidine compound into the desired substituent, e.g. reacting a 2-halo or 2-(free or etherified)-mercapto-pyrimidine with an amine or (b) forming the pyrimidine ring e.g. by reacting a mono-substituted guanidine with an a -cyano-b -oxo-propionic acid or its oxo or acid functional derivative, to give a 4 - hydroxy- or 4-amino-5-cyano-pyrimidine bearing a 2-amino-substituent. Substituents in the 2, 4 and/or 5-positions may be converted into desired substituents by standard methods e.g. a nitrile may be converted to an amide, thioamide or ester, a 4-hydroxyl group may be converted into a halogen substituent by treatment with a phosphorus halide, or a hydroxyl or mercapto group may be etherified.  Many products are described in which R is a dimethylamino, diethylamino, butylamino, N1-methylpiperazino or piperidino group, R1 is a hydroxy, chloro, methoxy, furfurylamino, N1-methylpiperazino, diethylaminoethylamino or o-methyl-o1-chloro-phenylmercapto group, R2 is a cyano, carbamoyl or thiocarbamoyl group and R3 is hydrogen or methyl.  2 - Methylmercapto-4-amino-5-cyano-pyrimidine and its 6-methyl derivative are made by reacting 5-methyl isothiourea hydriodide with ethoxymethylene-malonitrile or b -ethoxy-a -cyano-crotonitrile, respectively. 2-Methylmercapto-4-hydroxy-5-cyano-pyrimidine is made by reacting 5-methyl-isothiourea with ethoxymethylene-cyanoacetic ester and heating the resulting 5-methyl-isothioureidomethylene-cyano-acetic ester with aqueous sodium hydroxide.  Pharmaceutical preparations having tumourchecking, diuretic, coronary dilatating, analgesic, anti-rheumatic, anti-bacterial, fungicidal and anti-virus activity comprise the above compounds of the invention in admixture or conjunction with a pharmaceutical carrier.  The preparations comprise the active pyrimidine compounds or, their salts with inorganic or organic acids (including for example ascorbic, p-aminobenzoic and p-aminosalicylic acids, methionine, tryptophane, lysine and arginine) in association with conventional excipients for enteral, parenteral or topical administration suitably in the form of tablets, dragees, solutions, suspensions or emulsions. Specifications 884,151 and 886,184 are referred to.