Pyridazine ring, 3-amino

Pyridazine, 4-amino-3,6-dihalo-ring contraction, 3, 29 Pyridazine, 4-amino-3,6-dimethoxy-nitration, 3, 20... 

The linearly condensed pyridazino[6,l-A]quinazolines can be synthesized by tandem [6+0 (a)] cyclizations, forming the pyrimidine and the pyridazine rings in the same step. Thus, 1,2,3,4-tetrahydro-10//-pyridazino[6, l+]quinazolin-2,10-dione 108 was prepared by thermal cyclization of 106 or 107 (Scheme 12) <1999RJ0286, 1998RJ0534>. Heating/ra r-2-amino-l-cyclohexanecarbohydrazide with 3-(/>-chlorobenzoyl) propionic acid in toluene, the appropriate 2-(/<-chlorophenyl)-3,4,5 ,6,7,8,9,9 -octahydro-10//-pyridazino[6,l- ]quinazolin-10-one was prepared in 35% yield <1998JHC201>. 

The pyridazine ring of 111 is formed from [4+2] atom fragments in the cyclization of 3-amino-2-chloromethyl-quinazolin-4-one with activated acrylthioamides. The saturated pyridazine ring of 111 aromatized spontaneously to give 112 (Equation 12). Reaction with io-nitrostyrene yielded the 3-nitro analogue of 112 <2003MOL401>. 

Formation of the pyridazine ring occurs in a straightforward way from a suitably substituted pyrrole. Thus the pyrrole nucleoside (95) forms the pyrrolo[2,3-rf]pyridazine (96) on treatment with hydrazine <93JMC3834>. Another report describes the preparation of 4-amino-1 -(/i-o-ribo-furanosyl)pyrrolo[2,3-< /]pyridazine (Equation (30)) <91BMClll>. Similar pyrrole nucleosides, with an ester function at position 3 and an aldehyde at position 2, lead to 4-oxo derivatives upon treatment with hydrazine <90JHC1989>, or 4-amino derivatives with a cyano group at position 3 (92JMC526). 

A 2-bromo-acid derivative is the vital reagent. It reacts at the amino nitrogen atom with the carbonyl group and at the pyridazine ring nitrogen atom with the alkyl halide. This is the only way the molecule can organize itself into a ten-electron aromatic system. 

Pyridazinomycin (134) is a new antifungal antibiotic produced by Strep-tomyces violaceoniger. The amino acid side chain can be viewed as L-ornithine, whose end nitrogen atom is part of the pyridazine ring (88MI2). 

On addition of methyllithium in tetrahydrofuran/diethyl ether, pyrido[3,4-r/]pyridazine gives a 1 1 mixture of the two isomeric 1,2- and 4,3-addition compounds, i.e. 1-methyl-1,2-dihydropy-rido[3,4-r/]pyridazine (10) and 4-methyl-3,4-dihydropyrido[3,4-<7]pyridazine (11), which are readily oxidized by air to yield the fully aromatic systems (see Section 7.2.1.5.1.3).6 129 If the pyridazine ring is deactivated by amino substituents as in l,4-dimorpholino-7-phenylpyri-do[3,4-r/ pyridazine or its 5-methyl derivative, addition of organometallics such as benzyllithi-um, benzylmagnesium chloride or rcrt-butylmagnesium bromide occurs at the pyridine ring and yields 5-alkyl-5-methyl-l,4-dimorpholino-7-phenyl-5,6-dihydropyrido[3,4-d]pyridazines 12.119... 

Cyclization of /V- [2-(2-nitrobenzylidene)amino]phenyl acetamides 3 with potassium cyanide in methanol leads to quinoxalino[2,3-c]cinnolines 5 which also contain the pyrazino[2,3-c]-pyridazine skeleton. The reaction is supposed to proceed via the addition of hydrogen cyanide to the N —C double bond (formation of 4) followed by formation of the quinoxaline ring and finally closing of the pyridazine ring. The yields obtained are up to 62%.78... 

On boiling the methiodide with 70% sulfuric acid an N-methyl-oxo derivative was obtained, and this in turn gave 3-amino-2-phenyl-quinoline, methylamine, and ammonia on fusion with soda lime. The bulk of the evidence therefore favors quaternization at N-2 (cf, 154), in which case the acid-hydrolysis product is 155. Quaternization at N-2 would be expected because of the steric influence of the 10-phenyl group and the influence of the 4-amino group (cf. 4-hydroxy-pyridazine ) in the pyridazine-type ring, although the partial double-bond character of that ring is probably different from that in pyridazine itself. 

Amino 4-oxo 4//-pyrimido[l,2-4]pyridazin-3-diazonium tetrafluoroborates 73 underwent ring transformation into l-(pyridazin-3-yl)-l//-l,2,3-triazole-4-carboxylates 74 on heating in dry MeOH. Yields dropped drastically when EtOH, instead of MeOH, was used as solvent (Equation 6) <2002ARK143>. 

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