Abstract
The synthesis of a novel class of 6-amino-5-hydroxypyridazin-3(2H )-ones (3-oxo-2,3-dihydropyridazines) is described. These compounds also contain an
ethoxycarbonyl moiety at the 4-position of the pyridazinone ring. They are prepared
in good to moderate yields (30-72%) by the condensation of disubstituted amines with
(alkylhydrazono)- or (arylhydrazono)(chloro)acetates followed by subsequent acylation
with ethyl malonyl chloride and Dieckmann cyclization. An initial assessment of the
scope and limitations of the new methodology is described along with the novel synthesis
of several (alkylhydrazono)(chloro)acetate substrates utilized in the pyridazinone
preparations.
Key words
pyridazin-3(2H )-ones - Dieckmann cyclization - hydrazones - amino- and chloro(hydrazono)acetates
- heterocycles
References
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Unless otherwise noted, all hydrazones described in this work were isolated and characterized
as single isomers. No attempt was made to assign hydrazone stereochemistry (E or Z ) or to rigorously identify any minor amounts of alternate isomers that may have been
formed during a given synthetic transformation.
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Reversing the order of the chlorination and Boc-deprotection steps also afforded 3a , but in significantly lower yield.
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The major amino(hydrazono)acetate acylation products described in this work are inferred
to be those depicted in Scheme
[1 ]
(structure 5 ) by their successful conversion into 6-aminopyridazin-3(2H )-ones in reasonable yields (Scheme
[1 ]
, structure 6 ). Significant amounts of alternate acylation products were not detected by LCMS analysis
of the reaction mixtures and no other attempts were made to identify and/or quantify
such entities.
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The reaction was performed in an open flask. We have observed that the chlorination
rate and yield can vary with the source of the N -chlorosuccinimide employed in the reaction.