Patent GB-774095-A (GB)
Title: Improvements in or relating to pyrimidine compounds
IPC: C07D471/04
Filed: 1954-01-04
Abstract: The invention comprises substituted pyrido(2,3-d) pyrimidines of the general formula: <FORM:0774095/IV(b)/1> wherein X and Y represent alkyl- and dialkyl-amino groups having 1 to 5 carbon atoms and arylamino, amino and mercapto groups and X also represents a hydroxy group, R1 represents hydrogen or an alkyl group having from 1 to 5 carbon atoms or a phenyl group, and R2 and R3 represent hydrogen, alkyl groups having from 1 to 5 carbon atoms, and aralkyl and monocyclic aryl groups or R2 and R3 together represent the trimethylene or tetramethylene group, providing further that when any of R1, R2 and R3 are other than hydrogen Y may also represent a hydroxy group, and the preparation thereof by condensing, preferably by warming, a pyrimidine of the general formula: <FORM:0774095/IV(b)/2> wherein X and Y have the above significance, with a b -carbonyl aldehyde or ketone of the general formula: <FORM:0774095/IV(b)/3> wherein R1, R2 and R3 have the above signi ficance, in an aqueous acidic medium, e.g. 85 per cent phosphoric acid, or concentrated sulphuric acid.  Suitable pyrimidine reactants for use in the above process are 2,6-diamino-, 2,6-dihydroxy-, 2-amino-6-hydroxy- and 2-mercapto-6-hydroxy-pyrimidines.  Pyrido (2,3-d) pyrimidines of the above general formula, wherein R1, R2 and R3 have the above significance and X and Y represent hydroxy groups, or X represents a hydroxy group and Y represents a mercapto group, may also be prepared by reacting a 2-amino-nicotinic acid of the general formula: <FORM:0774095/IV(b)/4> wherein R1, R2 and R3 have the above significance, with urea when X and Y represent hydroxy groups, and with thiourea when X represents a hydroxy group and Y represents a thio group.  The pyrido-(2,3-d) pyrimidines of the above general formula in which X and Y represent hydroxy groups may be further treated with phosphorus oxychloride to replace both hydroxy groups by chlorine atoms and the resulting 2,4 - dichloro - pyrido - (2,3 -d) pyrimidine, e.g. 2,4-dichloro-5,6,7-trimethyl- or 2,4-dichloro - 7 - methyl - pyrido - (2,3 - d) pyrimidine, is then reacted with (a) ammonia or a primary or secondary lower alkylamine or an arylamine to form a 2,4-diamino-pyrido-(2,3-d) pyrimidine of the above general formula, or (b) a metallic hydrosulphide, e.g. sodium hydrosulphide, to form a 2,4-dimercaptopyrido- (2,3-d) pyrimidine of the above general formula which may also be prepared by reacting a 2,4-dihydroxy-pyrido-(2,3-d) pyrimidine with phosphorus pentasulphide.  A 2-mercapto-4-hydroxypyrido-(2,3-d) pyrimidine of the above general formula may also be prepared by reacting the 2,4-dichloropyrido-(2,3-d) referred to above with aqueous alkali metal hydroxide to form a 2-chloro - 4 - hydroxy - pyrido - (2,3 - d) pyrimidine, e.g. 2 - chloro - 4 - hydroxy - pyrido (2,3 -d) pyrimidine, which is then treated with (a) sodium hydrosulphide to form a 2-mercapto-4-hydroxy - pyrido - (2,3 - d) - pyrimidine of the above general formula which may also be obtained by treating a 2-mercapto-4-aminopyrido-(2,3-d) pyrimidine with hydrochloric acid, or (b) ammonia or the required amine and heated to form a 2-amino-4-hydroxy-pyrido-(2,3-d) pyrimidine of the above general formula.  A 2 - mercapto - 4 - aminopyrido - (2,3 - d) pyrimidine of the above general formula may also be prepared by treating the 2,4-dimercapto-pyrido-(2,3-d) pyrimidine referred to above with ammonia or by treating the 2,4-dichloropyrido-(2,3-d) pyrimidine referred to above with ammonia to form a 2-chloro-4-amino-pyrido-(2,3-d) pyrimidine, e.g. 2-chloro-4-amino-pyrido-(2,3-d) pyrimidine, which is then treated with a metallic hydrosulphide.  The preferred pyrido-(2,3-d) pyrimidine products of the above general formula are 2,4-diamino-pyrido-(2,3-d) pyrimidine and the corresponding compounds containing 7 - methyl -, 5,7 - dimethyl -, 6,7 - trimethylene -, 6,7 - tetramethylene -, 6 - ethyl - 7 - n-propyl -, and 7 - phenyl - substituents, and 2,4-dimercapto-pyrido-(2,3-d) pyrimidine.  In the examples a large number of pyrido-(2,3-d) pyrimidine products of the above general formula are referred to in which X and Y represent amino, anilino, dimethylamino, hydroxy and thio groups, R1 represents hydrogen and the methyl group, R2 represents hydrogen and the methyl, ethyl, n- and iso-propyl, n-butyl and phenyl groups, R3 represents hydrogen and the methyl, ethyl, n-propyl, n- and iso-butyl, benzyl, p-tolyl and p-chloro- and p-bromophenyl groups, and R2 and R3 together represent the trimethylene and tetramethylene groups.