| abstract |
A three-step process is provided for preparing the L,D and DL isomers of N[p-{[(2,4-diamino-6-pteridyl)-methyl]N 10 -methylamino}-benzoyl]-glutamic acid. The first step produces: 2,4-diamino-6-hydroxymethyl pteridine by condensation in a buffered aqueous media of 2,3,4,5-tetraminopyrimidine dihydrochloride with the bisulphite addition product of 1,3-dihydroxyacetone in the presence of cysteine as catalyst and using selenium dioxide and a continuous air bubbling as oxidation agents. In the next step, 2,4-diamino-6-halomethylpteridine is obtained by halogenation of the previously obtained 2,4-diamino-6-hydroxymethylpteridine in an inert media with a halogenation agent such as thionyl chloride, in the presence of a basic catalyst such as pyridine or triethylamine. In the third step, N[p-{[(2,4-diamino-6-pteridyl)-methyl]-N 10 -methylamino}-benzoyl-]-glutamic acid is produced by condensation of the 2,4-diamino-6-halomethylpteridine with N[p-(N-methylamino)-benzoyl]-glutamic acid at pH 3-4 in an aqueous buffered solution. |