Patent GB-640092-A (GB)
Title: Improvements relating to the preparation of substituted pteridines and intermediatesthereof
IPC: C07D475/04
Filed: 1946-07-26
Abstract: Substituted pteridines having in at least one tautomeric form the formula <FORM:0640092/IV (b)/1> wherein R represents OR1 or NR2R3, R1 being a hydrogen atom or an alkyl group and R2 and R3 being a hydrogen atom or an aliphatic group, are prepared by admixing (i) 2 : 4 : 5-triamino-6-hydroxypyrimidine or a tautomer thereof; (ii) reductone (2 : 3-dihydroxy acrylaldehyde) or a tautomer thereof, or mucohalic acid (a  : b -dichloro-b -formyl acrylic acid) or an ester or a tautomer thereof; (iii) para-aminobenzoic acid or a salt, aliphatic ester, an aliphatic amide thereof or para-aminobenzamide. Reactants (i) and (ii) may be mixed and the reaction product then reacted with reactant (iii), or reactants (ii) and (iii) may be mixed and the reaction product thereof reacted with reactant (i).  The reaction may be carried out in water, or in an inert organic solvent, preferably a hydroxylated organic liquid such as ethyl alcohol or ethylene glycol, or in solvents such as acetone, benzene or formamide. Alkaline condensing agents such as sodium acetate or formate, disodium phosphate, pyridine or dimethylaniline may be added to the reaction mixture.  The preferred mucohalic acids are mucobromic and mucochloric acids.  Suitable esters of muchalic acids are the methyl, ethyl, propyl and butyl esters.  Suitable amides of benzoic acid may be derived from an aminoacid, e.g. glutamic and aspartic acids and leucine, alanine, iso-valine and cysteine.  The aminoacid may contain one or more peptide linkages, e.g. glutamylglutamic, glutamylglutamylglutamic and glutamylglycylglutamic acids.  The aminoacids may be natural or synthetic, and may be in the d, l or dl forms.  The salts and esters of the aminoacids may be employed in lieu of the free acid.  Acid salts of the pteridines of the above general formula may be prepared by the addition of a mineral acid, e.g. hydrochloric or sulphuric acid.  Cation salts may be obtained by treating the pteridines with an alkali such as an alkali metal hydroxide, ammonia or an amine, and by double decomposition methods to introduce cations such as zinc, silver, nickel, copper, magnesium or barium.  A number of detailed examples are given.  Substituted propenylidenes of the formula <FORM:0640092/IV (b)/2> wherein R is OR1 or NR2R3, R1 being hydrogen atom or an alkyl group, and R2 and R3 being hydrogen atoms or aliphatic groups, are prepared by reacting reductone with paraaminobenzoic acid or a salt, an aliphatic ester or an aliphatic amide or para-aminobenzamide.  The reaction product may be reacted with 2 : 4 : 5-triamino-6-hydroxypyrimidine to give substituted pteridines of the above general formula.  A number of detailed examples are given.  The Specification as open to inspection under Sect. 91 refers to the preparation of substituted pteridines of the general formula <FORM:0640092/IV (b)/3> wherein R is OR1 or NR1R11, R1 and R11 being hydrogen or aromatic or aliphatic radicals, by mixing in any order or together: (i) 2 : 4 : 5-triamino-6-hydroxypyrimidine or a tautomer thereof; (ii) a substituted propenal having attached to each one of the carbon atoms adjacent the double bond a halo or hydroxy radical, and hydrogen or a radical convertible to hydrogen on the terminal carbon atom; (iii) an aminobenzoic acid, or a salt, ester or amide thereof.  Substituted propenylidenes of the formula <FORM:0640092/IV (b)/4> wherein R is OR1 or NR1R11, R1 and R11 being hydrogen or aromatic or aliphatic radicals, are prepared by reacting reductone with an aminobenzoic acid or a salt, ester or amide thereof.  This subject-matter does not appear in the Specification as accepted.