2-Amino-6-methylpyridine Nalidixic acid

A 1,8-naphthyridine, nalidixic acid (39), shows clinically useful antibacterial activity against Gram-negative bacteria as such, the drug is used in the treatment of infections of the urinary tract. Condensation of ethoxymethylenemalonate with 2-amino-6-methylpyridine (36) proceeds directly to the naphthyri-dine (38) the first step in this transformation probably involves an addition-elimination reaction to afford the intermediate, 37. W-Ethylation with ethyl iodide and base followed by saponification then affords nalidixic acid (39). 

An antibacterial agent made from the intermediate 2-amino-6-methylpyridine (124) is nalidixic acid (125) used for treatment of the urinary tract (Scheme 26)76. An aminopyrim-idine intermediate is used in the synthesis of trimethoprim, 5-(3,4,5-trimethyoxybenzyl)-2,4-diaminopyrimidine (126) (Scheme 27), useful for treatment of infections of the urinary tract and the chest. Unlike antibiotics, there is no build up of bacterial resistance to this drag. 

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