Patent GB-854959-A (GB)
Title: Pyrimidine compounds and means of producing the same
IPC: C07D487/04
Filed: 1958-04-03
Abstract: The invention comprises compounds of the general formula: <FORM:0854959/IV(b)/1> and acid addition salts thereof, wherein R represents a hydrogen atom, or an-NH2, -NH (acyl), -NH(lower aliphatic), benzylamino, halobenzylamino, -N(lower alkyl)2, anilino, -S(lower alkyl), piperidino, morpholino, or pyrrolidino radical, R1 represent v (lower aliphatic) (wherein the lower aliphatic radical, which can be open or cycloaliphatic can be a hydrocarbon, hydroxy- or alkoxy hydrocarbon radical), -NH(aralkyl) (wherein the aralkyl radical can be a hydrocarbon or a halo-, hydroxy-, alkoxy- or aminohydrocarbon radical) -NH(heterocyclic-substituted alkyl), anilino, -OH or -SH radical and R2 represents a hydrogen atom, or where R1 is an -NH2 or -OH radical, R2 is to represent a hydrogen atom or an -NH2, -NH (lower alkyl), -S (lower alkyl), -OH, or lower alkyl radical and wherein "lower alkyl" and "lower aliphatic" represent C1-6 alkyl and aliphatic groups.  The compounds of the invention are prepared by reacting a 4-amino pyrimidine of the formula:  <FORM:0854959/IV(b)/2> with a carbonyl or carbonyl related compound such as a urea, guanidine, amidine carboxylic acid anhydride, acid halide, amide, or ortho carboxylic acid ester; and wherein X represents a cyano, carbamoyl or carbalkoxy group, when X is a cyano group the reaction being carried out with an amide, such as formamide or with a guanidine or amidine, when X is a carbamoyl radical, with a urea carboxylic acid anhydride, acid halide, amide or ortho carboxylic acid ester, and when X is a carbalkoxy radical with amide or a urea.  Compounds of the invention wherein R represents an alkylthio and R1 represents a hydroxy group are also obtained by the reaction of guanidine or an isothiourea compound with alkyl 2-(alkylthio)-4-halopyrimidine-5-carboxylates; compounds of the formula:  <FORM:0854959/IV(b)/3> are prepared by reacting the corresponding pyrimido [4,5-d]pyrimidin-5-ol compounds with phosphorus pentasulphide in the presence of a basic solvent such as pyridine; compounds of the formula:  <FORM:0854959/IV(b)/4> by reacting the corresponding pyrimido [4,5-d] pyrimidines-5-thiols, with an amine of the formula R11NH2, where R11 represents a hydrogen atom or a phenyl, lower alkyl, aralkyl, or heterocyclic-substituted alkyl radical; compounds of the formula:  <FORM:0854959/IV(b)/5> by reacting compounds of the formula:  <FORM:0854959/IV(b)/6> with R11NH2 wherein R4 represents an-OH, -NH2, NH (lower alkyl), -NH (aralkyl), or anilino radical, and R3 represents a hydrogen atom, or where R4 is an -NH2 or -OH radical R3 represents a hydrogen atom or an amino or lower alkylthio radical and R11 has the meaning defined above except where R3 is a lower alkylthio radical R11 is a hydrogen atom or a lower alkyl radical, R5 being being the same as R3 except where R3 is a lower alkylthio radical R5 represents an -NH2 or -NH (lower alkyl) radical; and compounds of the formula: <FORM:0854959/IV(b)/7> by heating a compound of the formula: <FORM:0854959/IV(b)/8> with formic acid or a trialkylorthoformate and an amine R111NH2 wherein R111 represents a hydrogen atom or a lower aliphatic or cycloaliphatic radical which may be hydroxy or alkoxy substituted, a [phenyl-aryl] or an aralkyl radical which may be halo, amino hydroxy or alkoxy substituted or a heterocyclic-substituted alkyl radical, R6 being the same as R which is defined above, with the proviso that when R represents S (lower alkyl), R6 represents NHR111 and when R represents NHAcyl, R6 represents -NH2. 2:4-Diamino-, 4-amino-2-methylamino-, 4-amino-2-allylamino-, 4-amino-2-anilino-, 4-amino-2-dimethylamino-, and 4-amino-2-benzylamino-5-pyrimidine carboxamides are prepared by hydrolysis of the correspondingly substituted 5-cyanopyrimidines; 4-amino-2-allylamino-and 4-amino-2 -dimethylamino-5-cyano pyrimidines are prepared by reacting allyl guanidine hemisulphate or 1,1-dimethylguanidine with ethoxymethylene malononitrile in the presence of sodium methoxide; 4-amino-2-anilino-, 4-amino-2-piperdino-, and 4-amino-2-benzylamino-5-cyanopyrimidines are prepared by reacting an appropriate amine with 4-amino-2-(ethylthio)-5-cyanopyrimidine.