Pyridazine, Negishi cross-coupling reactions

In 2002, Wonnacott published the synthesis and biological evaluation of a pyridazine analog (62) of nicotinic acetylcholine receptor agonist UB-165 [45]. This aza-UB-165 analog (62) was synthesized via Negishi cross-coupling reaction on triflate 60 with pyridazin-3-ylzinc halide (59). Compound 59 could be obtained from 3-bromopyridazine (58) via lithiation and subsequent transmetalation with zinc chloride. 

In the frame of a medicinal chemistry program at Merck Sharp Dohme Ltd, Collins and co-workers reported successful Negishi cross-coupling reaction of 3-aryl-7-bromo-6-[( 1 -methyl-1/7-1,2,4-triazol-5-yl)methoxy][ 1,2,4]triazolo[4,3-/ pyridazines (63) with aliphatic organozinc reagents [35]. 

Queguiner prepared the first Negishi cross-coupling reaction of a pyridazine. 3,6-Dimethoxypyridazine (60) was lithiated and transmetallated with zinc chloride at the 4-position to give zinc species 61, which underwent smooth cross-couplings with a few halides to give pyridazinyl compounds... 

Negishi cross-coupling reactions of pyridazines have also been utilized in the synthesis of analogs of nicotinic acetylcholine receptor agonists and anxiolytic drugs with improved side-effect profiles." ... 

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