Substituent-Driven SelectiveN-/O-Alkylation of4-(Trihalomethyl)pyrimidin-2(1H)-ones Using Brominated Enones

The selectiveN-orO-alkylation of 4-(trihalomethyl)-pyrimidin-2(1H)-ones, using 5-bromo enones/enaminones as alkylat-ing agents, is reported. It was found that the selectivity toward theN-orO-regioisomer is driven by the substituent present at the 6-positionof the pyrimidine ring, thus enabling the preparation of each isomeras the sole product, in 60-95% yields. Subsequent cyclocondensationof the enaminone moiety with nitrogen dinucleophiles led topyrimidine-azole conjugates in 55-83% yields.

Automated summary

Selective N- or O-alkylation of 4-(trihalomethyl)-pyrimidin-2(1H)-ones using 5-bromo enones/enaminones as alkylating agents is reported. The selectivity towards the N- or O-regioisomer is determined by the substituent at the 6-position of the pyrimidine ring, allowing the preparation of each isomer as the sole product in yields of 60-95%. Subsequent cyclocondensation of the enaminone moiety with nitrogen dinucleophiles leads to pyrimidine-azole conjugates with yields of 55-83%.