The Synthesis of 7-Substituted-2,3-dihydropyrido [4,3-d]pyridazine-1,4-diones and 1,4-Dioxo-7-substituted-1,2,3,4-tetrahydropyrido[4,3-d]pyridazine 6-Oxides from Methyl Ketones.

Benjamin Prek,Branko Stanovnik

doi:10.17344/acsi.2017.3695

Abstract

A general four-step transformation of alkyl, cycloalkyl, aryl, and heteroaryl methyl ketones via 3-(dimethylamino)-1-substituted-prop-2-en-1-ones, followed by microwave [2+2] cycloaddition of dimethyl acetylenedicarboxylate, cyclization of (2E,3E)-2-[(dimethylamino)methylene]-3-(2-substituted)succinates with ammonia or hydroxylamine hydrochloride into 2-substituted-pyridine-4,5-dicarboxylates and their N-oxides and final cyclization with hydrazine hydrate into of 7-substituted-2,3-dihydropyrido[3,4-d]pyridazine-1,4-diones and 1,4-dioxo-7-substituted-1,2,3,4-tetrahydropyrido[4,3-d]pyridazine 6-oxides is shown.

Highlights

There are several methods for the preparation of 2,3-dihydro[4,3-d]pyridazine-1,4- dione derivatives
These are transformed by treatment with N,N-dimethylformamide dimethyl acetal (DMFDMA) or tert-butoxybis(dimethylamino)methane (Brederecks reagent) into the corresponding 3-(dimethylamino)-1-substituted-prop-2-enones, which are further transformed in a regiospecific microwave assisted [2 + 2] cycloaddition with dimethyl acetylenedicarboxylate (DMAD)[25] to the before mentioned 1,3-butadienes
In this communication we report a general and simple synthesis of 7-substituted-2,3-dihydropyrido[3,4-d] pyridazine-1,4-diones 6a-c,f and 1,4-dioxo-7-substituted-1,2,3,4-tetrahydropyrido[4,3-d]pyridazine 6-oxides 7a, b,d,e,g from methyl ketones 1a-g

Summary

Introduction

There are several methods for the preparation of 2,3-dihydro[4,3-d]pyridazine-1,4- dione derivatives. The functionalized buta-1,3-dienes as the basis of the synthetic route presented in this paper are prepared from simple and commercially available compounds such as alkyl, aryl, and heteroaryl methyl ketones These are transformed by treatment with N,N-dimethylformamide dimethyl acetal (DMFDMA) or tert-butoxybis(dimethylamino)methane (Brederecks reagent) into the corresponding 3-(dimethylamino)-1-substituted-prop-2-enones, which are further transformed in a regiospecific microwave assisted [2 + 2] cycloaddition with dimethyl acetylenedicarboxylate (DMAD)[25] to the before mentioned 1,3-butadienes. We reported a simple, metal-free synthesis of electron rich 2,4,6-trisubstituted pyridine derivatives[28] and the synthesis of polysubstituted benzene derivatives, where N,N-dimethylacetamide dimethyl acetal (DMADMA) served as the reagent and building block for generating aromatic final products.[29,30] Our existing knowledge of the enaminones and 1,3-butadienes has been expanded to the synthesis of pyridines starting from Boc-protected amino acids, and the results of our research are presented in this paper

Results and Discussion

Experimental

Conclusion

Reference