Synthesis of amino-5-arylsulfonylpyrimidines

Several new 4-amino-5-arylsulfonylpyrimidines were prepared via the reaction of various α-(ethoxymethylene)arylsulfonylacetonitriles with guanidine or variously substituted amidines (Table II). 2,4-Diamino-5-(p-chlorophenylsulfonyl)pyrimidine (IIIg), a typical example, was prepared from the reaction of 2-(p-chlorophenylsulfonyl)-3-ethoxyacrylonitrile (IId) with guanidine in refluxing ethanol containing sodium ethoxide. With proper substitution of the ethoxymethylene intermediate, the method was found suitable for the preparation of other compounds having either a hydroxy or methyl group at the 4-position of the 5-arylsulfonylpyrimidine. The fluoro group in 2,4-diamino-5-(p-fluorophenylsulfonyl)pyrimidine (IIIx) was successfully replaced by nucleophilic reagents such as sodium ethoxide, N-methylpiperazine and N,N-diethylethylene-diamine. Attempts at direct displacement of fluorine by ammonia at 190° were unsuccessful.