Pyridazine ring synthesis

Ring Synthesis of Fused Pyridazines, Pyrimidines, and Pyrazines with Oxygen, Sulfur,... 

Ring synthesis via the transformation of 3-amino-277-pyran-2-ones (including fused derivatives) have been further investigated <2006H(70)235, 2006T9718>. 3-Amino-2//-pyran-2-ones could be transformed into the corresponding pyridazine-3-carboxylates via reaction with hydrazine followed by oxidation of the carbohydrazide moiety and 1,4-dihydropyridazine nucleus with CAN. 

Two complementary routes to the synthesis of pyrido[, y-i/ pyridazines have been developed, the first of which begins by constructing the pyridine ring, and the second by constmcting the pyridazine ring. In addition, ring transformations of pyrrolopyridine, pyridooxazine, pyridopyrimidine, and tetrazine derivatives to the pyrido[x,y-t7 pyridazines have also been reported. 

The imidazo-pyridazine ring system forms the basis for a number of drugs in human and animal medicine. The synthesis of this system uses chemistry discussed in Chapter 43 to build the pyridazine ring. There we established that it was easy to make dichloropyridazines and to displace the chlorine... 

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. 

Romero-Salguero, F.J., and Lehn, J.-M., Synthesis of multitopic bidentate ligands based on alternating pyridine and pyridazine rings. Tetrahedron Lett., 40, 859, 1999. 

Jacoby (187) and the Hamilton group (188-191) suggested that bis- or tris-aromatic residues could serve as scaffolds for helical mimetics. Che et al. have examined a variety of aromatic-based scaffolds as potential helix mimetics (192). Rebek and coworkers have suggested a central pyridazine ring (193) as well as a heterocyclic piperazine-based scaffold (194). Ahn and Han developed a facile synthesis of benzamides as potential helix mimetics (195). 

Ring synthesis of such molecules can proceed from diazines nsing methods analogous to those described for the synthesis of azolo-pyridines from pyridines, for example the dipolar cycloaddition of an A-imide to an alkyne, or the bromine-promoted ring closure of hydrazones of 2-hydrazino-pyridines, -pyridazines (shown) or -pyrimidines. ... 

Letsinger and Lasco6 reported the first authenticated synthesis of the pyrrolol l,2-6]pyridazine ring system. These authors demonstrate that, in methanol solution, pyridazines (192) would react readily with dimethyl acetylenedicarboxylate to give 5,6,7-tricarbomethoxypyrrolo-... 

Although pyridazine and pyrazine A-oxides can be readily prepared by oxidation of the parent heterocycles, pyrimidine A-oxides are more difficult to obtain in this way but they can conveniently be prepared by ring synthesis. ... 

Ring synthesis of pyridazines I I.I4.I.I From a 1,4-dicarbonyl compound and a hydrazine... 

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). ... 

The same research group reported on synthesis of [2]rotaxane employing Diels-Alder reaction of terminal alkyne with 1,2,4,5-tetrazine to provide stopper units (Scheme 8.2) [11]. Synthetic concept is identical as in the previous example. Two components in acetonitrile after evaporation gave pseudorotaxane 9, which was subjected to ball milling with ym-tetrazine 10. After 9h, [2]rotaxane 11 was obtained in high yield. Silica gel was added to facilitate transformation in solid state. Under mechanochemical solvent-free conditions, small, but sufficiently bulky pyridazine rings were used for stoppering the pseudorotaxanes. 

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