1.2.4- Triazolo pyridazine, 6-chloro

Matsuda et al. <1995H(41)2777> described an efficient synthesis of mesoionic [l,2,4]triazolo[4,3-A]pyridazines 390 and 391. The starting compound for the synthesis is the A-aminotriazole 389, which can be treated either with ethyl 2-chloro-3-ethoxyacrylate to yield 390 or with ketene dithioacetals to afford 391. The reactions proceed in good to high yield. 

Triazolo[4,3-6]pyridazine (1404) was prepared in 75% yield, in the cyclocondensation of 3-chloro-6-hydrazinopyridazine and EMME in boiling acetonitrile for 3 hr, or in 94% yield in the cyclization of hydrazinomethy-lenemalonate (195) in boiling acetonitrile for 4 hr (80JHC1527). 

Two methods for the preparation of [l,2,3]triazolo[4,5-, pyridazine-4-thione 29 were reported by Bussolari et al. involving nucleophilic substitution of sulfur by displacement of the 4-chloro substituent from 28 and of the oxygen atom of 4-lactam derivative 30 using sodium thiosulfate and phosphorus pentasulfide, respectively (Scheme 18) <1996BMC1725>. 

This ring system, often viewed as 2,8-diaza-3-deazapurine, and some of its derivatives have been prepared by diazotization of the appropriate 4,5-diaminopyridazine (69JHC93,70CPB1685) as Scheme 44 represents for the formation of (15) itself. There are no other practical syntheses for this series of compounds. A similar approach has been used for preparing the isomeric [l,2,3]triazolo[4,5-c]pyridazines with the 7-chloro derivative being a useful compound (67JHC555). 

Although this route has not been used extensively there are several examples. The synthesis of 3-aryl-7-bromo-6-chloro[l,2,4]triazolo[4,3- ]pyridazines (39) from 3-aryl-6-chloro-... 

Substituted 4,S-dihydropyridazin-3,6-dione 3-hydrazones were reacted with trifluoroacetic acid to yield 3-trifluoromethyl-s-triazolo[4,3-6]pyri-dazinones (19) [94M1(49)21]. Reaction of catechol derivatives with 3,4,5-tri-chloropyridazine have been shown to afford 4-chloro[l,4]benzodioxino[2,3-c]-pyridazines 20 and 21 [93JHC(30)789]. An efficient procedure for preparing phenyl 3-pyridazinyl ketones 22 has been published [93JHC(30)1685] [94SC(24)773],... 

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