Substituent-Driven Selective N -/ O -Alkylation of 4-(Trihalomethyl)pyrimidin-2(1 H )-ones Using Brominated Enones.

The selective N - or O -alkylation of 4-(trihalomethyl)pyrimidin-2(1 H )-ones, using 5-bromo enones/enaminones as alkylating agents, is reported. It was found that the selectivity toward the N - or O -regioisomer is driven by the substituent present at the 6-position of the pyrimidine ring, thus enabling the preparation of each isomer as the sole product, in 60-95% yields. Subsequent cyclocondensation of the enaminone moiety with nitrogen dinucleophiles led to pyrimidine-azole conjugates in 55-83% yields.