Regioselective Suzuki-Miyaura Reactions of Ethyl 2,6-Dibromo- pyrazolo[1,5-a]pyrimidine-3-carboxylate

A variety of novel disubstituted pyrazolo[1,5-a]pyrimidine derivatives have been prepared via sequential site-selective cross -coupling reactions of ethyl 2,6-dibromopyrazolo[1,5-a]pyrimidine-3-car-boxylate. The regiocontrolled Suzuki-Miyaura reaction proceeded with excellent selectivity in favor of position C6 after careful optimization of the cross-coupling conditions. The monobrominated compounds, obtained on a large scale, were subjected to a second arylation, alkynylation or amination, leading to a new series of ethyl 2,6-disubstituted pyrazolo[1,5-a]pyrimidine-3-carboxylates. These results constitute an efficient regioselective approach for diversification of the chemically and biologically interesting pyrazolo[1,5-a]pyrimidine heterocycle at C2 and C6 positions.

Automated summary

A range of new disubstituted pyrazolo[1,5-a]pyrimidine derivatives were synthesized via sequential site-selective cross-coupling reactions of ethyl 2,6-dibromopyrazolo[1,5-a]pyrimidine-3-carboxylate. After careful optimization, the regiocontrolled Suzuki-Miyaura reaction exhibited excellent selectivity at position C6. The monobrominated compounds were further transformed through arylation, alkynylation, or amination, leading to a novel series of ethyl 2,6-disubstituted pyrazolo[1,5-a]pyrimidine-3-carboxylates. This approach provides an efficient regioselective method for diversification of the chemically and biologically interesting pyrazolo[1,5-a]pyrimidine heterocycle at positions C2 and C6.