Issue in Honor of Prof. Albert Padwa ARKIVOC 2002 (viii) 143-156
N N H2NOC Cl N NPh N H Me N N O Cl H2N PhNH2 COOH N O N N NH MeO S NH2 O O Pyridazomycin Minaprine Chloridazone Sulfamethoxypyridazine (antifungal antibiotic)(antidepressant)(herbicide)(antibacterial)
N
Me Me3SiO
Me
N
N
N
N
H N
N CHO
N N
N
N
Et N N OMe Cl 1H-Benzotriazole (synthetic auxilliary)(muscarinic receptor ligand)(fluorescent whitening agent)(photostabilizer)
Figure 1
On the other hand, alkyl 2-substituted 3-(dimethylamino)propenoates have proved to be easily available and efficient reagents for the preparation of various heterocyclic systems.4 For example, acid-catalyzed reactions of alkyl 2-acylamino-3-(dimethylamino)propenoates with various o-aminoazines and o-aminoazoles leads to the corresponding alkyl N-acyl-2,3-dehydro3- heteroarylalaninates and azino-and azolo-fused 3-acylamino-4H-pyrimidin-4-ones. Deprotection of the 3-acylamino group gives free amines, usually in good yields. Similarly, 3amino- 4H-quinolizin-4-ones have been prepared from alkyl 2-acylamino-3( dimethylamino)propenoates and 2-pyridinylacetic acid derivatives.4–6 Nitrosation of such heteroarylamines gives the corresponding heteroaryldiazonium salts, which are suitable precursors for further transformations.7,8 In this manner, methyl (Z)-2-benzyloxycarbonylamino3-( dimethylamino)propenoate (1) has been transformed in three steps into 1-substituted 4-oxo4H- quinolizine- and 4-oxo-4H-pyrido[1,2-a]pyrimidine-3-diazonium tetrafluoroborates. Heating of 4-oxo-4H-quinolizine-3-diazonium salts in primary alkanols resulted in aza Wolff rearrangements to give the corresponding alkyl indolizine-3-carboxylates,7 while 4-oxo-4Hpyrido[ 1,2-a]pyrimidine-3-diazonium tetrafluoroborates underwent, under the same reaction conditions, a ‘ring switching’ transformation to afford the corresponding alkyl 1-(4-substituted pyridin-2-yl)-1H-1,2,3-triazole-4-carboxylates.8
Owing to the extensive use of pyridazine-and 1,2,3-triazole- derivatives in various applications, it seemed reasonable to focus our studies in this field also on synthesis and transformations of 3-amino-4H-pyrimido[1,2-b]pyridazin-4-ones. In this paper, we report the preparation of 3-benzyloxycarbonylamino-4-oxo-4H-pyrimido[1,2-b]pyridazine derivatives 3a–g, 3-amino-4-oxo-4H-pyrimido[1,2-b]pyridazines hydrobromides 4d,e,g, 4-oxo-4H-pyrimido[1,2b] pyridazine-3-diazonium tetrafluoroborates 5a,e, and ‘ring switching’ transformations of
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