GB631494A - Improvements in or relating to the preparation of 2-amino-4-hydroxy-6-substituted pteridines - Google Patents

Abstract

2 - Amino - 4 - hydroxy - 6 - substituted pteridine is prepared by mixing a 2-amino-4-hydroxy-6-halomethyl-pteridine with p-amino-benzoic acid or a salt, ester or amide thereof in an inert and preferably anhydrous solvent, e.g. an alcohol or alkylene glycol. The reaction mixture may be heated to a temperature between 80 DEG and 150 DEG C. Suitable amides of p-aminobenzoic acid are p-aminobenzoylglutamic acid, p-aminobenzoylaspartic acid and p-amino benzoylglycine, and amides of aminoacids having one or more peptid linkages such as p-amino-benzoylglutamylglutamic acid. In examples, pteroylglutamic acid and its diethyl ester are prepared. The ester groups may be removed by hydrolysis. Methyl - gamma, gamma - dimethoxy acetoacetate is prepared from dimethoxy acetate, sodium and methyl acetate by a method similar to that given in the journal of the American Chemical Society, Volume 41, page 812. 2 - Amino - 4 - hydroxy - 6 - pyrimido-[4, 5-b]-pyrazine acetic acid is prepared by heating 2 : 4 : 5-triamino-6-hydroxypyrimidine and methyl-gamma, gamma-dimethoxy acetoacetate in glacial acetic acid. 2 - Amino - 4 - hydroxy - 5 - methyl pteridine is obtained by heating 2-amino-4-hydroxy-6-pyrimido - [4, 5-b] - pyrazine acetic acid. 2 - Amino - 4 - hydroxy - 6 - (mono - and di-bromomethyl)-pteridines are obtained by heating 2 - amino - 4 - hydroxy - 6 - methyl pteridine in a sealed tube with bromine. The mono-bromo derivative may be obtained merely by heating with bromine and hydrobromine acid. 2 - Amine - 4 - hydroxy - 6 - (chloromethyl)-pteridine is obtained by heating 2-amino-4-hydroxy-6-methyl pteridine with sulphuryl chloride in the presence of benzoyl peroxide.