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The synthesis of 5,10-dideazaaminopterin by two independent routes is described. Condensation of the piperidine enamine of 4-p-carbomethoxyphenylbutyraldehyde (4) with ethoxymethylenemalononitrile followed by treatment of the resultant arylethylenaminomalononitrile (5) with methanolic ammonia produced 2-amino-3-cyano-5-p-carbomethoxyphenethylpyridine (6). Cyclization of the aminocyanopyridine with guanidine afforded 4-amino-4-deoxy-5,10-dideazapteroic acid (8). Coupling of the pteroate intermediate with glutamate yielded the target 5,10-dideazaaminopterin (10). Alternatively, reduction of 2,4-diamino-6-formyl-5-deazapteridine (11) with sodium borohydride gave the 6-hydroxymethyl compound 12. Conversion to the bromide was followed by alkylation of dimethyl homoterephthalate to afford methyl 4-amino-4-deoxy-10-carbomethoxy-5,10-dideazapteroate (14). Decarboxylation with ester cleavage (sodium cyanide in dimethyl sulfoxide at 180°) also gave the diaminopteroic acid (8). 5,10-dideazaaminopterin (10) was an effective growth inhibitorof folate dependent bacteria, S. faecium and L. casei.