2-Aminopyridine, reaction with

Substitution of a 2-pyridyl residue for the phenyl attached rectly to nitrogen affords a series of potent antihistamines, eparation of these compounds, too, is accomplished by a series alkylation reactions. It is further probable that the order the reaction can be readily interchanged. Thus, alkylation 2-aminopyridine with the chloroethyldimethylamine side chain ads to the diamine, 59. Alkylation with benzyl chloride af-rds tripelenamine (60) reaction with p-methoxybenzyl chloride ads to pyrilamine (61), °... 

Resorting to alkylation chemistry again, 2-aminopyridine is condensed with the usual side chain halide to give diamine, 74. Alkylation of this with 2-chloromethylthiophene gives methapyrilene (75). Reaction with 2-chloromethyl-5-chlorothiophene affords the potent antihistamine chlorothen (76). ... 

Chloropyridine undergoes reaction with dimethylamine to yield 4-dimethyl-aminopyridine. Propose a mechanism for the reaction. 

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). 

Aminopyridotriazinones 123 were obtained from guanidines 122 in hot hydrochloric acid-dioxane solution however, yields were moderate. The intermediates 122 could be obtained from the reaction of 2-aminopyridine 120 with ethoxycarbonyl isothiocyanate, followed by treatment of thioureas 121 with amines in the presence of HgCl2 (Scheme 12) <2002JHC1061>. 

Reaction of the benzotriazole-linked aminopyridine 503 with 2,3-dihydrofuran and boron trifluoride etherate results in cyclization to the furopyridopyrimidinium salt 504 with loss of benzotriazole (Equation 221) <1998S704>. 

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). 

Conversion of aromatic amines to azides was studied by Scechter et al. <2002TL8421> and these studies lead to the recognition of a new approach to tetrazolo[l,5- ]pyridine. Thus, reaction of 2-aminopyridine 142 with butyl-lithium followed by treatment with azidotris(diethylamino)phosphonium bromide gave rise to tetrazolo[l,5- ]pyr-idine 1 in 80% yield. The first intermediate is obviously the azide 7. 

If di(tcrt-butyl)nitroxide (a radical trap) is present, the reaction with phenylacetonitrile-potassium does not proceed entirely. Acetonitrile-potassium (which is in equilibrium with potassium amide) forms only aminopyridine in the presence of the trap (Moon et al. 1983). Consequently, amination is a classical nucleophile reaction, and the formation of pyridyl acetonitrile is a reaction of the typs- These two reactions are quite different. A stronger CH acid leads to a well-defined synthesis. 

There is a complication if the nucleophile used in reactions with halopyridines is also a strong base for now the formation of a pyridyne is possible, and with sodamide in liquid ammonia (providing the NH2 ion , B), for example, both 3-aminopyridine and 4-aminopyridine are formed from 4-bromopyridine (Scheme 2.16). 

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