Patent GB-1004289-A (GB)
Title: Pyrimidine compounds and methods for their production
IPC: C07D209/56
Filed: 1963-04-18
Abstract: The invention comprises salts of 2,4-diamino-5 - (p - chlorophenyl) - 6 - ethyl - pyrimidine with any of the following acids: an acid of formula <FORM:1004289/C2/1> where X is a 51-methylene (61-hydroxy-21-naphthoic acid), 41 - methylene (11 - hydroxy-21 - naphthoic acid), 41 - (31 - hydroxy - 21-naphthoic acid, 41 - benzylidene (31 - hydroxy - 21 - naphthoic acid), 41 - ethylidene (31 - hydroxy - 21 - naphthoic acid, 41 - methylene (71, 81 - dibromo - 31 - hydroxy - 21 - naphthoic acid, or a 3-carboxy-4-hydroxybenzyl radical; or an acid of formula <FORM:1004289/C2/2> where Y is a 41-(71-bromo-31-hydroxy-21-naphthoic acid), 41 - methylene (71 - bromo-31 - hydroxy - 21 - naphthoic acid, 41 - methylene (31 - hydroxy - 21 - naphthoic acid), 41-methylene - (11 - hydroxy - 21 - naphthoic acid), 51 - methylene (61 - hydroxy - 21 - naphthoic acid), 41 - methylene (71, 81 - dibromo - 31 - hydroxy - 21 naphthoic acid), or 3 - carboxy - 4-hydroxybenzyl radical; an acid of formula <FORM:1004289/C2/3> where Z is a 41-(11-hydroxy-21-naphthoic acid), 41 - methylene (11 - hydroxy - 21 - naphthoic acid), 41 - benzylidene (11 - hydroxy - 21 - naphthoic acid), or 41 - methylene (71, 81 - dibromo - 31 - hydroxy - 21 - naphthoic acid) radical; an acid of formula <FORM:1004289/C2/4> where B is a 41-methyl (71, 81-dibromo-31-hydroxy - 21 - naphthoic acid), 41 - (71, 81 - dibromo - 31 - hydroxy - 21 - naphthoic acid), 51 - methylene (61 - hydroxy - 21 - naphthoic acid), or 3-carboxy-4-hydroxybenzyl radical; an acid of formula Ar-S-Ar, where Ar is 4 - (3 - hydroxy - 2 - naphthoic acid); an acid of formula Ar-SO2-Ar, where Ar is 5-(2-hydroxybenzoic acid); an acid of formula <FORM:1004289/C2/5> where each A is independently hydrogen, halogen or nitro; the acids of formula <FORM:1004289/C2/6> and their preparation as exemplified, comprising reaction of the components or their soluble salts.  4,41 - Dihydroxy - (1,11 - binaphthalene) - 3, 31-dicarboxylic acid 6,61 - dibromo - 2,21 - dihydroxy (1,11 - binaphthalene) - 3,31 - dicarboxylic acid and 5,51,6,61-tetrabromo-2,21-dihydroxy (1,11 - binaphthalene) - 3,31 - dicarboxylic acid are prepared by treating the substituted naphthoic acids in aqueous sodium hydroxide with ferric chloride and treating the product with hydrochloric acid.  4,41 - Methylene bis compounds of 7 - bromo-3 - hydroxy - 2 - naphthoic acid 1 - hydroxy - 2-naphthoic acid and 7,8-dibromo-3-hydroxy-2-naphthoic acid are prepared by condensing the naphthoic acids with formaldehyde: 4,41-ethylidenebis(3 - hydroxy - 2 - naphthoic acid) is prepared by condensation using paraldehyde and 4,41 - benzylidenebis (1 - hydroxy - 2-naphthoic acid) by condensation using benzaldehyde.  Other 4 - substituted - 3 - hydroxy - 2 - naphthoic acid starting material with optional bromosubstituents are prepared by reacting the 4-chloromethyl - 3 - hydroxy - 2 - naphthoic acid methyl ester with the appropriate acid to form the monomethyl ester of the starting material which is then obtained by hydrolysis.  7 - Bromo - 4 - chloromethyl - 3 - hydroxy - 2-naphthoic acid methyl ester is prepared from the 4-unsubstituted compound with formalin and hydrochloric acid.  Pharmaceutical compositions comprise salts of the invention with diluents and excipients. Forms (solutions, suspensions, ampoules) for parenteral administration against malaria are mentioned.  Reference has been directed by the Comptroller to Specification 715,813.