Imidazo pyridazin-7-ones

The imidazo-pyridazine ring system forms the basis for a number of drugs in human and animal medicine. The synthesis of this system uses the chemistry discussed in Chapter 29 to build the pyridazine ring. There we established that it was easy to make dichloropyridazines and to displace the chlorine atoms one by one with different nucleophiles. Now we wiU move on from these intermediates to the bicyclic system. 

Imtdazo[4,5-d]pyridaztne, l-benzyl-4,7-dtchloro-nucleophtlic displacement reactions, 5, 629 Imidazo[l,5-6]pyridazine-5,7(3H,6H)-dione, 4-acetyl-2-phenyl-synthesis, 5, 651 Imidazo[l, 2-6]pyridazines reactions, 5, 628 synthesis, 5, 650 Imidazo[ 1,5-6]pyridazines synthesis, 5, 651 Imidazo[4,5-c]pyridazines reactions, 5, 628-629 synthesis, 5, 651 Imidazo[4,5-d]pyridazines reactions, 5, 629 synthesis, 5, 436, 468, 651-652 3H-Imidazo[l,2-6]pyridazin-2-one, 6-chloro-3-dichloromethylene-synthesis, 3, 355... 

Several interesting 1,2,4-triazole fused-ring systems have been reported. A facile synthesis of 3,5-dihydro-677-imidazo[l,2-fc]-l,2,4-triazol-6-ones 162 was obtained by an iminophosphorane-mediated annulation <06EJ04170>. 8-Trifluoromethyl-l,2,4-triazolo[4,3- >]pyridazines 163 has been prepared from 4-trifluoromethyl-4,5-dihydropyridazin-3-one... 

Several other azolopyridazine ring systems have been prepared by similar approaches <2002FA89, 2002JHC329, 2001MOL203, 2000MOL1187>. For example, 6-substituted imidazo[4,5-tf pyridazin-7-ones are obtained from the reaction of 1,2-disubstituted 4-aroylimidazole-5-carboxylates and hydrazines <2002JHC329>. 

When cyclization of the acrylamide (167) was attempted in refluxing 1,2,4-trichlorobenzene, 6-chloro-3-dichloromethylene-3//-imidazo[l,2-6]pyridazin-2-one (35) was formed instead of the expected pyrimido[1,2-6]pyridazin-4-one (34). The latter compound could be obtained by conducting the cyclization in refluxing xylene. Since (34) and (35) are in practice not thermally interconvertible (at 210 °C), it can be assumed that (34) is not a precursor in the formation of (35) (71JOC3506). 

Chemical synthesis of this ring system has been achieved by two basic methods. First, imidazoles with groups at the 4- and 5-positions capable of undergoing condensation to form the pyridazine ring have been employed. Second, 4,5-diaminopyridazines can be condensed with an appropriate one-carbon synthon to produce imidazo[4,5-<3Tlpyridazines. 

Mekonnen and co-workers present an intriguing route to 3-monosubstituted imidazo[l,2-b]pyridazine derivatives which are important motifs in several therapeutically interesting molecules.483 0 The key step involves a novel one-pot cyclisation/oxidation reaction under Swem oxidation conditions.49... 

A simple one-pot procedure for the synthesis of imidazo-[l,2-a]pyridines (13) involves a novel condensation reaction of l-(arylacetyl)imidazoles (12) with dimethyl acetylenedicarboxy-late (eq 18). " Functionalization of 13 with hydrazine hydrate affords the imidazo[l,6]pyrido[2,3-pyridazine ring system (14). ... 

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