Base Effect and Inhibition of Catalytic Activity in Palladium-Catalyzed N-Heteroarylation of Pyrazoles with 2,6-Dibromopyridine

Using the catalytic system Pd(OAc) 2 /PPh 3, coupling of 2,6-dibromopyridine ( 1 ) and pyrazoles ( 2 ) in a molar ratio of 1: 2:base = 1:2.4:2.5 afforded the monosubstituted compounds 3 as the major products when KO t Bu was used as the base. Without using the catalyst or using NaO t Bu as the base the disubstituted compounds 4 were formed as the major products in yields up to 93%. Reactions of 1 and 2 in a molar ratio of 1: 2:base = 1:1:1 selectively produced compounds 3 in yields up to 82% when KO t Bu was used as the base. The complex from the reaction of 3 and Pd(OAc) 2 did not undergo further reaction with 1 to form 4 in the presence of a base. The base effect and inhibition of catalytic activity for Pd(OAc) 2 are discussed.