Reaction of electrophiles at the amino group

1 Reaction of electrophiles at the amino group 8.01.7.10.1(0 Acyl halides or acid anhydrides as electrophiles 

Reaction of cinnolin-4-amine with pivaloyl chloride yielded the expected corresponding amide as well as a disub-stituted compound resulting from the reaction of 4-pivaloylaminocinnoline with a second molecule pivaloyl chloride at N-1 1995T13045 . Similarly, other amides have been made from 5-aminopyridazin-3(277)-ones 

Reductive alkylation is a well-known reaction in heterocyclic chemistry and has also successfully been executed on 1,2-diazinamines. The reaction of 6-aryl-5-aminopyridazin-3(27/)-ones with formalin and NaBH3CN as reductant for instance yields 6-aryl-5-dimethylaminopyridazin-3(2//)-ones 1998JHC1421 . 

Although 1,2-diazinamines are not very nucleophilic by themselves the nucleophilicity can be increased via initial deprotonation with strong base. This strategy has been followed by Heinisch and co-workers when studying intramolecular SNAr reactions (Equations 22 and 23) 1997H(45)673, 1997AP29 . 

Alkylation of 3-methoxycarbonylaminopyridazines with butynols under Mitsunobu conditions gave mixtures of side chain and ring alkylated products, which are difficult to separate, in a ratio of from 0.5-2 1 (Equation (22)). Other methods of direct alkylation using sodium hydride with alkyl halides and tosylates failed to afford any products 84JOC2240 . 

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