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The synthesis of pyrimido[4,5‐ c ]pyridazines and pyrimido[5,4‐ c ]pyridazines
Author(s) -
Nakagome Takenari,
Castle Raymond N.,
Murakami Hirotaka
Publication year - 1968
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570050414
Subject(s) - pyridazine , chemistry , formamide , triethyl orthoformate , carboxamide , nitrile , amide , stereochemistry , medicinal chemistry , organic chemistry , catalysis
The Hofmann reaction on 6‐methylpyridazine‐3,4‐dicarboxamide (1) gave a mixture of 3‐methylpyrimido[4,5‐ c ]pyridazine‐5,7‐dione (2), 3‐methylpyrimido[5,4‐ c ]pyridazine‐6,8‐dione (3) and an acid (4) of unknown structure. The Hofmann reaction on pyridazine‐3,4‐dicarboxamide (9) gave a mixture of pyrimido[4,5‐ c ]pyridazine‐5,7‐dione ( 10 ) and an acid ( 11 ) of unknown structure. The reaction of 3‐amino‐6‐methylpyridazine‐4‐carboxamide ( 18 ) with ethyl orthoformate gave 3‐methylpyrimido[4,5‐ c ]pyridazin‐5‐one ( 21 ). 4‐Aminopyridazine‐3‐carboxamide ( 36 ) upon fusion with urea gave pyrimido[5,4‐ c ]pyridazine‐6,8‐dione ( 37 ) while with ethyl orthoformate 36 gave pyrimido[5,4‐ c ]pyridazin‐8‐one ( 38 ). Pyrimido[5,4‐ c ]‐pyridazine‐8‐thione ( 39 ) was obtained by the action of phosphorus pentasulfide on 38. 4‐Amino‐3‐cyanopyridazine ( 16 ) when treated with formamide produced 8‐aminopyrimido[5,4‐ c ]‐pyridazine ( 41 ). The synthesis of 4‐aminopyridazine‐3‐carboxamide ( 36 ) and 4‐amino‐3‐cyanopyridazine ( 16 ), both key intermediates in the synthesis of the novel pyrimido[5,4‐ c ]pyridazine ring system was accomplished by the Reissert reaction of 4‐aminopyridazine‐2‐oxides and subsequent conversion of the nitrile to the amide.