A general and mild method for the synthesis of 2, 4-diamino-5-benzylpyrimidines was achieved by the Friedel-Crafta reaction between 2-(methoxymethylene)-3- methoxypropanenitrile (10) and an activated aromatic substrate followed by treatment with guanidine. The method is illustrated by a synthesis of ormetoprim (2) in 75% overall yield from 3, 4-dimethoxytoluene (12). Efficient syntheses of trimethoprim (1) and 2 were also ...
