Alkynylation of halopyridazines and their N-oxides.

Palladium-Catalyzed Reactions on 1,2-Diazines

“…Only poor results were obtained since starting material could be recovered after a reaction time of 15 hours. piperidino) of the 3-chloropyridazine, only poor results were obtained with significant amounts of starting material that could be recovered [53]. Nevertheless, the authors subsequently focused on the 3-chloropyridazine derivatives for further optimization because of their better availability.…”

“…The iododerivative is more reactive than the corresponding chloropyridazine, which is in accordance with the expected oxidative addition rate. Also 3chloropyridazine 1-oxide (210) and 3-chloro-6-methylpyri- dazine 1-oxide (211) could be used as substrates in this reaction type (Table 25) [51,53]. Better results could be achieved for Sonogashira coupling of 3-chloro-6-methylpyridazine (204) with phenylacetylene, by performing the reaction at a higher temperature in less diethylamine using a higher catalyst loading.…”

“…Nevertheless, the authors subsequently focused on the 3-chloropyridazine derivatives for further optimization because of their better availability. However, 3chloropyridazine 2-oxides were surprisingly unreactive [53]. Subsequently, several 6-substituted 3-chloropyridazines (16,18) were heated at 50 to 70°C with several acetylenes under these optimized conditions, allowing a good access to the corresponding 3-alkynylpyridazines (205-209) ( Table 24) [51,52].…”

“…Interestingly, the authors also reported that the use of propargyl alcohol gave no alkynyl substituted pyridazine upon coupling with 3-chloro-6-methylpyridazine (204) but instead, N,N-diethyl-2-methylpyrrolo [1,2-b]pyridazin-7-amine (216) was obtained in 49% yield (Scheme 22) [52,53]. When the reaction was executed at a lower temperature (30°C) for 4 hours starting from more reactive 3-iodo-6methylpyridazine (203), the expected 3-(6-methylpyridazin-3-yl)prop-2-yn-1-ol (217) could be isolated in 48% yield (Scheme 23) [53].…”

Palladium catalyzed reactions on chloropyridazines

“…The success of these palladium-catalyzed reactions is highly dependent on the substrate, the organometallic reagent or amine, the base (if present) and the ligand that is used for the palladium catalyst. For example, we [32] and others [23,24,33] described smooth Suzuki arylations on chloropyridazines with in situ generated Pd(0)(PPh 3 ) 2 catalyst, while the same substrates with the same catalytic system usually give moderate to bad results in the Sonogashira alkynylation [34][35][36].…”