Pyridazines. XXXVII. Novel triazanaphthalene derivatives via intramolecular cyclization reactions of vic‐disubstituted pyridazines

Abstract

8‐Phenylpyrido[3,4‐d]pyridazines bearing various amino substituents at C‐5 (7a‐d, 8) were prepared from ethyl 5‐benzyl‐4‐pyridazinecarboxylate 1 via the fused pyridone 5. The isomeric 4‐phenylpyrido[2,3‐d]pyridazines having the amino functions attached to C‐2 (10a‐f) were obtained by a one‐pot cyclization of the amino ketone 1 with appropriate acetamide acetals. These novel triazanaphthalene derivatives are of interest as analogues of diuretic and antithrombotic agents.

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

“…[1][2][3][4] Cyclization of ethyl 3-cyanoisonicotinate with hydrazine proceeds at room temperature to give 4-aminopyrido [3,4-d]pyridazine-1(2H)-one, 5,6 while pyridine-3,4-dicarbonitriles give the corresponding pyrido [3,4-d]pyridazine-1,4-diones. 7 Other methods include cycloamination of 4-carbofunctional-5-vinylpyridazines, ,8,9 condensation of 4,5-dicarbofunctional pyridazines with amines, 9,10 condensation of 4-(iminomethyl)pyridazines with enolates, 10 intramolecular cyclization of pyridinecarbohydrazides, 1,11 intramolecular cyclization of 4-vinylpyridazine-5-carbonitriles, 12,13 by ring enlargement of furo [3,4-c]pyridine-1,3-diones, 2,3,5,14,15 1H-pyrrolo[3,4-c] pyridine-1,3(2H) -diones with hydrazine, 1,4,16,17 by reaction of 5H-pyrano [3,4-d]pyridazines with amines, 8 intramolecular [4+2]cycloaddition of 1,2,4,5-tetrazines, 18 ring contraction of 2H-1,2,4-triazepines.…”