Pyrazolopyridazines. synthesis

H-Pyrazolo[ 1,2-u]pyrazol-4-ium chloride, 2,3,6,7-tetrahydro-synthesis, 6, 1012 Pyrazolopyridazines synthesis, 5, 322, 326 tautomerism, 5, 309 Pyrazolo[ 1,2-a]pyridazines hydrogenation, 5, 328 reactions... 

The literature on these ring systems in the last 10 years is vast. An Internet search alone provides 3500 citations for sildenafil (60a, Viagra). Not only Viagra is of medical interest allopurinol (ALP) 61, the classical treatment of gout arthritis, is still of interest, and pyrazolopyridazines and thiazolopyridazines have also been shown to be of biological importance. These activities extend beyond an interest in the synthesis and chemistry of these compounds indicated by the large number of patented potential applications. 

Plenty of such routes devoted to the synthesis of pyrazolo[3,4- / pyrimidines, pyrazolo[4,3-tf pyrimidines, as well as pyrazolopyridazines are described in CHEC-II <1996CHEC-II(7)431>. This route is still extensively utilized. Thus, reacting 253 with the amidine acetate 254 in refluxing ethanol yielded 255 (Equation 29) <2006BML731> yields of individual derivatives were not given. 

Thermal electrocyclic reactions of 1-azahexatriene systems can be used to obtain imidazo[4,5-c]pyridines (25) [95H(41)161] and the thermal cyclisation of 2-alkynylbenzene-diazonium salts (the Richter reaction) has been extended to the synthesis of pyrazolopyridazines (26) (Scheme 17) [95LA775],... 

Only one synthesis of this ring system by this route has been reported <77GEP2632656>. Cyclizing derivatives (452), prepared by treating (450) with hydrazine and subsequent treatment of the product (451) with DMF DMA, affords the pyrazolopyridazines (453) (Scheme 47). 

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