GB730139A - Improvements in or relating to the preparation of halogenated substituted pteridines - Google Patents

Abstract

31,51-Dihalogenopteridines having in one tautomeric form the general formula <FORM:0730139/IV (b)/1> wherein R represents a hydroxyl radical or -COR is an amide radical derived from an aliphatic amino acid and Z represents two like halogen atoms, are prepared in the form of their hydrohalide salts by producing pteridines of the general formula <FORM:0730139/IV (b)/2> wherein R has the above significance, by the method of Specification 657,903, i.e. by mixing (i) a 2,4,5,6-tetra-aminopyrimidine or a tautomer thereof or an acid salt thereof; (ii) an a b -dihalogenopropionaldehyde or an acetal thereof or 1,1,3-trihalogenoacetone; and (iii) the required primary aromatic amine, and treating the pteridines thus produced with substantially two molecular proportions of halogen. The reaction is carried out preferably in a solvent, e.g. an aqueous solution of a mineral acid to which the halogen may be added as a gas or in a solvent such as acetic acid. The halogen may also be liberated in situ with the aid of hydrogen peroxide. The reaction temperature for the halogenation may be within the range of -10 DEG to 35 DEG C. The hydrohalide salts may be converted into the ammonium and magnesium salts by reaction with aqueous ammonia or magnesia. In the examples the following compounds are prepared: salts of 31,51-dichloro-and dibromo-pteroylglutamic acid, 31,51-dichloro - 4 - aminopteroylaminomalonic acid, 31,51 - dichloro - 4 - aminopteroyl - dl - isoleucine and 31,51-dichloro-4-aminopteroyl-dl-valine. 4-Aminopteroylaminomalonic acid is prepared by reacting 2,4,5,6-tetra-aminopyrimidine sulphate, 4-aminobenzamidomalonic acid and 2,3-dibromopropionaldehyde. 4-Aminopteroyl-dl-isoleucine is prepared by reacting 2,4,5,6 - tetra - aminopyrimidine sulphate, 4 - aminobenzoyl - dl - isoleucine and 2,3-dibromopropionaldehyde. 4-Aminopteroyl-dl-valine is prepared as above using 4-aminobenzoyl-dl-valine.