2- Aminopyridine, derivative

Use of a (Substituted) Aminopyridine Derivative in Which the Nitro Group is Already Present in the Pyridine Ring as Starting Material... 

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. 

Reaction of pyridinium-A -(2-pyridyl)amidine (402) and alkyl haloace-tates in the presence of K2CO3 afforded a mixture of 4-oxo-4/f-pyrido[l, 2-u]pyrimidine-2-carboxylates 407 and 2-aminopyridine derivatives 406 through intermediers 403- 05, as depicted in Scheme 15 (00TL5837). Compound 406 could be cyclized on the action of heat or silica gel into 407. The best yield was achieved in the case of ethyl bromoacetate. 

The formation of 1-aminopyridinium chloride has been accomplished by the acid hydrolysis of N- ( -acetaminobenzene-sulfonimido)pyridine.4 Also, the rearrangement of a substituted diazepine has been observed to give a 1-aminopyridine derivative.5 The present procedure is an adaptation of that described by GosI and Meuwsen.1... 

Directed metallation continues to be developed as a convenient method for regiospecific substitution of pyridines. A mild and general procedure for the preparation of structurally diverse 4-alkyl-2-aminopyridines 37 involves the lithiation/alkylation of aminopyridine derivative 36 <96JOC(61)4810>. 

Table 6.48 5,6-DIARYL 2-AMINOPYRIDINE DERIVATIVES - IN VITRO BINDING...

The tremendous scope of utilization of DMAP and PPY as catalysts has led to an active interest in the development of their polymeric analogs. The pioneering work was carried out by Hierl et al (8) and Delaney et al. (9). They attached 4-dialkyl-aminopyridine derivatives to poly(ethyleneimine) and found the modified polymers to be highly active catalysts for hydrolysis of p-nitrophenylcarboxylates. Since then, many research groups have reported the synthesis of polymers functionalized with 4-dialkyl-aminopyridine (10-18). 

Rifaximin (4-deoxy-4/-methylpyrido[l, 2 -l,2]imidazo-[5,4-c]rifamycin SV, fig. 2) is a synthetic product designed to modify the parent compound, rifamycin, in order to achieve low GI absorption while retaining good antibacterial activity [37]. It is a rifamycin SV derivative, prepared by condensing 2-aminopyridine derivatives to 3-bromorifamycin S (fig. 3) [37-39]. This pyridoimidazo rifamycin SV derivative, which proved to be stable in gastric juice for 24 h, displays a zwitterionic nature at physiological pH [38]. 

The 5-, 6-, and 7-azaindoles were synthesized via the Pd-catalyzed heteroannulation of internal alkynes using orf/w-aminopyridine derivatives in an extention of Larock s indole synthesis [169], LiCl was found to be an essential component in order to obtain regioselectivity, reproducibility and improved yields. 

The ring closure of 3-pyridylaminomethylenemalonates may lead to 1,5-naphthyridine or 1,7-naphthyridine, depending on which position of the pyridine ring (position 2 or 4) is involved in the cyclization (Scheme 45). Due to the higher reactivity of position 2 of 3-aminopyridine derivatives... 

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. 

The more recent 4-azaquinolizin-l-one synthesis by Katritzky etal. (81JCS(P1)1495) appears more versatile. A 2-ethoxycarbonyIpyrylium salt (275 Scheme 134) is allowed to react with the hydrazone of acetophenone or of a p-substituted acetophenone (276). The methyl group of the resulting 1-aminopyridine derivative (277) is acidic and, when treated with potassium carbonate, generates an anion which attacks the ethoxycarbonyl group to afford the 4-azaquinolizin-l-one derivative (278) in good yield. 

The diazepine (98) also reacted with base to give a 2-aminopyridine derivative but via a quite different process (71JOC2676). 

Thieno-pyridopyridine isomers were prepared by the coupling of a halogenated aminopyridine derivative and formyl-thienylboronic acid. The coupling of the unprotected reagents led to the concomitant formation of the carbon-nitrogen and carbon-carbon bonds in good yield (4.2.),3... 

Thermolysis of hydrazine (767) in toluene-methanol catalyzed by TFA led to a translocative rearrangement to give the 2-aminopyridine derivative (768) (88JOC5309). 

Some 2-aminopyridine derivatives (107 and 108) were formed, also. Of the Schiff bases, only the benzaldehyde derivative reacted, yielding the 4-hydroxypyrido[l,2-a]pyrimidine (109), which was then oxidized with o-chloranil to the 4-oxo compound. 

The condensation of 2-aminopyridine derivatives 64 with ethyl cya-noacetate gave amides 65, which were cyclized to 2//-pyrido[l,2-a] pyrimidin-2-ones 66 by the treatment of triethyl orthoformate and acetic anhydride (90IZV229). 

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,... 

Intramolecular acylations of the Friedel-Crafts type will also take place with 3-aminopyridine derivatives but usually require either stringent conditions or the presence of further activating groups in the pyridine nucleus. The report that the acid 191 can be converted into... 

An unusual replacement of a pyridinium moiety in 70 by hydrogen has also been successful with (TMS SiH under normal radical conditions. In fact, the two substrates in equation 31 afforded 3-fluoro-2-aminopyridine derivatives in good yields80. 

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