Pyrimido 4,5-c pyridazine-5,7 -diones

Pyrimido[4,5-c]pyridazine-5,7-dione, 3-aryl-6,8-dimethyl-synthesis, 3, 357... 

JOC6503>, and new pyridazino-psoralens 15 were prepared via a furan ring expansion reaction <05T4805>. The reaction of 3-acetylcoumarins with alloxan followed by NH2NH2 easily produced 3-(2-oxo-2//-chromen-3-yl)-6//,8//-pyrimido[4,5-c]pyridazine-5,7-diones <05JHC1223>. Furano- and pyrano[2,3-c]pyridazines 17 and 18a,b as well as substituted quinolines were conveniently prepared from pyridazinone 16 and vinyl- and allyltriphenyl-phosphonium salts <05HAC56>. 

Pyridazine-3,4-dicarboxamide (187) undergoes the Hofmann reaction followed by ring closure to give pyrimido[4,5-c]pyridazine-5,7-dione (188) as the major product. In an analogous type of ring closure, 3-amino-6-methylpyridazine-4-carboxamide reacts with ethyl orthoformate to give 3-methylpyrimido[4,5-c]pyridazin-5-one (68JHC523). 

The synthesis of 4-trifhioromethylpyrimido[4,5-c]pyridazin-5,7-diones from 6-hydrazinouracils and l,l,l-trifluoropropane-2,3-dione monohydrates has been reported <06H1875>. Novel pyrimido[4,5-c]pyridazines have been synthesized and investigated as inhibitors of lymphocyte specific kinase <06BMCL4257 06H2037>. 

Reaction of 3-alkylamino-6,8-dimethylpyrimido[4,5-c]pyridazin-5,7-diones 80 with cyclohexyl and cycloheptylamines afforded novel cycloalkano bis(pyrrolo[2,3-c]pyrimido[5,4-e]pyridazines 81 <06T652>. 

Much of the recently reported work on nucleophilic substitution at C-3 and C-4 of pyrimido[4,5-f]pyridazine-5,7-diones is included in a review of nucleophilic substitution in pyridazines <2001CHE1461>. 6,8-... 

Hydrazino-l,3-dimethyluracil (185) reacts with phenacyl bromides in DMF to give the corresponding 3-aryl-6,8-dimethylpyrimido[4,5-c]pyridazine-5,7-diones (186). 6-Benzyl-idenehydrazino-l,3-dimethyluracils are also known to react with DMF dimethyl acetal to give pyrimido[4,5-c]pyridazines (78JHC781). 

Another facile synthesis of pyrimido[4,5-c]pyridazin-5,7(6/7,8//)-diones (51), pyrimido[4,5-c]py-ridazin-5(8//)-ones (52), and dihydropyrimido[4,5-c]pyridazin-5(6//)-ones (53) starts from 3-chloro-4-pyridazinecarbonitrile (48) via aminocarbonitriles (49) and aminocarboxamides (50) (Scheme 9). Cyclization of the latter with urea at high temperatures affords the pyrimido[4,5-c]pyrid-azin-5,7(6/7,8//)-diones (51). By heating of the carboxamides with aromatic aldehydes the dihydropyrimido[4,5-c]pyridazin-5(6/7)-ones (52) are obtained <88JHC119). 

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