Reaction with aminopyridine derivatives

Of derivatives of compound 3, the zwitterions 245 react with DMAD if magnesium bromide is added to give aminopyridine derivatives (00H(53)265). Compounds such as 102 are opened by acid to give quaternary pyridinium salts (92LA885). There are various interconversions of 2-substituted triazolopyridin-3-ones into 1-substituted zwitterions. An example is the reaction of 246 (83BCSJ2969) the reverse conversion is also reported. 

In a similar way, 1,3-dinitrogen systems such as diamines, amidines, guanidines, aminothiazoles, aminopyridines, ureas and thioureas react with alkynyl-carbene complexes generating the corresponding heterocycles. Of particular interest is the reaction with ureas, as the process can be applied to the easy synthesis of pyrimidine derivatives [88] (Scheme 41). 

The parent heterocycle of pyrido[2,3-e][l,2,4]triazine and its phenyl derivative 39 were prepared (89JHC475) by cyclization with polyphos-phoric acid of 3-acyIhydrazino-2-aminopyridines 36, obtained by reduction of the corresponding 3-acylhydrazino-2-nitropyridines 35. Compounds 35 were obtained from 3-fluoro-2-nitropyridine 34 either by reaction with benzoylhydrazine or by reaction with hydrazine and subsequent for-mylation of the initially formed 3-hydrazino-2-nitropyridine 38. Attempts to prepare 38 from 3-chloro-2-nitropyridine gave 2-hydrazino-3-chloropyridine 37. These results could be explained by semiempirical calculations (CNDO and MNDO calculations). 

Some unusual transformations will follow. The term unusual refers to unexpectedly smooth processes of H atom replacements obtained with (TMS)3SiH under radical conditions. Reaction (4.42) reports the replacement of a pyridinium moiety by hydrogen, with (TMS)3SiH under standard experimental conditions using t-BuOH as the solvent. In fact the two substrates (R = Me, Et) afforded 3-fluoro-2-aminopyridine derivatives in good yields [78], leaving the fluorine substituent untouched. 

Several thiazolo[4,5- >]pyridines, which may be considered as 2-protected-3-aminopyridines, undergo 4-deprotonation and provide, by reaction with a variety of electrophiles, good yields of functionalized products 231 (Scheme 68) (89TL183). In the case of the 6-chloro derivative 230, exclusive formation of the 4-substituted product 231 was observed. 

Other related distonic superelectrophiles (200-201) were also shown to provide acyl-transfer products with benzene, and in the case of the aminopyridine derivative (202) intramolecular reaction produces the indanone (eq 69). 

The 4-aminopyridine derivative 92, prepared from the reaction of ethyl benzoylacetate and malononitrile dimer 91, undergoes the coupling reaction with aromatic diazonium salts to afford azo derivatives such as 93. Under refluxing conditions in ethanolic sodium hydroxide, these azo compounds cyclize to pyrido[3,2-f]pyridazines and pyrido[3,2-r]-pyridazino[2, 3 - ]quinazolines (Scheme 15) <2005AP329>. 

The almost exclusive ring closure at the a-position carries over to other electrophilic reactions of substituted 3 -aminopyridine derivatives. For example, the condensation of 3-aminopyridine with ethoxy-methylenemalonic ester (EMME) in dilute solution in boiling Dowtherm A gave the 1,5-naphthyridine 190.425,426 The only exception to date is that of 3-aminopyridine A -oxide which, as expected,... 

Boc derivatives of pyrroles.1 Base-sensitive pyrroles can be converted into the 1-Boc derivative by reaction with (Boc)20 in CH3CN or CH2C12 catalyzed by 4-dimethyl-aminopyridine. Triethylamine can be used as a base, but is not usually required. Yields are generally >80%. 

The aza-Wittig reaction of iminophosphoranes 60 with isocyanates affords the carbodiimides 61, which undergo ring closure to give 2-aminopyridine derivatives 62. ... 

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