Synthesis of 6‐substituted pyrimidines by the wittig reaction. I. Via 2‐amino‐4‐hydroxy‐5‐phenylbutylpyrimidine‐6‐carboxaldehyde

Condensation of isopropyl 6‐phenylhexanoate with ethyl diethoxyacetate followed by guanidine afforded 2 ‐ amino‐6‐diethoxymethyl‐5‐phenylbutyl‐4‐pyrimidinol (VII). Acid hydrolysis of VII gave an excellent yield of 2‐amino‐4‐hydroxy‐5‐phenylbutylpyrimidine‐6‐carboxaldehyde (IV); the latter could be condensed with stabilized Wittig reagents such as carbethoxymethylene triphenyl phosphorane and cinnamylidene triphenyl phosphorane, but not unstabilized Wittig reagents such as carbethoxypropylene or cyano‐propylene triphenyl phosphorane. Reduction of the Wittig products afforded pyrimidines with functionalized side‐chains in the 6‐position such as the 6‐phenylbutyl (XVIII) and 6‐carboxyethyl (XV) derivatives of 2‐amino‐5‐phenylbutyl‐4‐pyrimidinol.