Diastereoselective Synthesis of Dimethyl (4R*,4a′R*,7a′R*)-1-Aryl-6′-benzoyl-4a′-methyl-5-oxo-1,4′,4a′,5,5′,6′-hexahydrospiro[pyrazole-4,7′-pyrrolo[3,4-c]pyridazine]-3′,7a′(1′Η)-dicarboxylates

Abstract

Methyl (Z)-2-(benzoylamino)-3-(dimethylamino)propenoate (1) reacted with trimethylenemethane (2) to produce methyl (Z)-2-[benzoyl(2-methylallyl)amino]-3-(dimethylamino)propeno­ate (3), which was then converted into pyrazole derivatives 11a-h by a consecutive exchange of the dimethylamino group with hydrazine derivates 9a-h and cyclization to the ester group. Reactions of pyrazoles 11a-g with dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate (6) resulted in the diastereoselective formation of 1-aryl-6′-benzoyl-4a′-methyl-5-oxo-1,4′,4a′,5,5′,6′-hexahydrospiro[pyrazole-4,7′-pyrrolo[3,4-c]pyridazine]-3′,7a′(1′H)-dicarboxylates 12a-g. This represents a simple new pathway to novel heterocyclic systems. On the other hand, when (dimethylamino)propenoate 3 reacted with aniline hydrochloride (4), followed by the cycloaddition of 1,2,4,5-tetrazine 6, dimethyl (E)- and (Z)-4-({benzoyl[1-(methoxycarbonyl)-2-(phenylamino)vinyl]amino}methyl)-4-methyl-1,4-dihydropyridazine-3,6-dicarboxylates (7) and (8) were formed, respectively.

Key words

spiro[pyrazole-4,7′-pyrrolo[3,4-c]pyridazine] - 1,2,4,5-tetrazine - heterocycles - diastereoselectivity - cycloadditions

References

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Crystallographic data for compound 3 in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 689402. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, CB2 1EZ, UK [fax: [phone] or e-mail: [e-mail]].

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Crystallographic data for compound 12a in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 689403. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, CB2 1EZ, UK [fax: [phone] or e-mail: [e-mail]].