Alain Turck

We report herein the ‘metal-halogen exchange’ reaction in the diazine series with lithium tri-n-tributylmagnesate. The ­reaction was performed with 2-iodopyrazine, 2-methylsulfanyl-4-iodopyrimidine and 3-iodo-6-phenylpyridazine. Benzophenone, ­aldehydes and diphenylsulfur were used as electrophiles affording alcohols and phenylsulfanyl derivatives with satisfactory to good yields.

The regioselectivity of the metalation of 2‐chloro‐6‐methoxypyrazine, 2‐fluoro‐6‐methoxypyrazine and 3‐fluoro‐6‐chloropyridazine was studied; the relative ortho‐directing power was F > OMe > Cl.

Functionalized iodopyridines bearing either a chloride, ester or nitrile function were converted to the corresponding organomagnesium derivatives at -40 °C or -78 °C by treatment with i-PrMgBr (1.1 equiv, 0.5 h, > 90% yield). The resulting functionalized Grignard reagents react with aldehydes, TosCN directly or with allylic bromides and benzoyl chloride after transmetalation with CuCN leading to polyfunctional pyridines.

A new route to aminodiazines is reported, the ortho-directed lithiation of diazines is used, followed by reaction with tosyl azide as an electrophile. The reduction of the azido or tetrazolo compounds obtained was achieved and led to the expected amines. This methodology has allowed the synthesis of new aminodiazines and an improvement in the yield of various aminodiazines previously described. This reaction was used for the preparation of an aza analogue of Nevirapine.