2-Amino pyridine, reaction with

Amino and sulfur analogues of pyrazolones also yield the aromatic quaternary salt (231 X = NH or S). If the pyrazole bears a substituent with a second pyridine-like nitrogen atom, an intramolecular bridge can be formed by reaction with a dihalogenoalkane. Thus pyrazol-I -ylpyridines react with 1,2-dibromoethane to form (233) (81JHC9). 

The Zincke reaction has also been adapted for the solid phase. Dupas et al. prepared NADH-model precursors 58, immobilized on silica, by reaction of bound amino functions 57 with Zincke salt 8 (Scheme 8.4.19) for subsequent reduction to the 1,4-dihydropyridines with sodium dithionite. Earlier, Ise and co-workers utilized the Zincke reaction to prepare catalytic polyelectrolytes, starting from poly(4-vinylpyridine). Formation of Zincke salts at pyridine positions within the polymer was achieved by reaction with 2,4-dinitrochlorobenzene, and these sites were then functionalized with various amines. The resulting polymers showed catalytic activity in ester hydrolysis. ... 

The indirect deactivation in 2-amino-4-chloroquinoline (187) requires vigorous conditions (potassium hydroxide in hot ethylene glycol, or boiling propanolic propoxide for 16 hr) to displace the chloro group, which is stable to aqueous alkali and to hydriodic acid. The direct deactivation in 5-amino-2-chloro-3-cyano-6-methyl-pyridine (188) prevents reaction with alkoxide ion under conditions which produce smooth reaction of the des-amino analog. 

Xanthobacter sp. strain Py2 may be grown with propene or propene oxide. On the basis of amino acid sequences, the monooxygenase that produces the epoxide was related to those that catalyzes the monooxygenation of benzene and toluene (Zhou et al. 1999). The metabolism of the epoxide is initiated by nucleophilic reaction with coenzyme M followed by dehydrogenation (Eigure 7.13a). There are alternative reactions, both of which are dependent on a pyridine nucleotide-disulfide oxidoreductase (Swaving et al. 1996 Nocek et al. 2002) ... 

Furthermore, oxazoles of type 9-82 bearing a secondary amino functionality can be converted into pyrrolo[3,4-b]pyridines 9-86 by reaction with appropriate acid chlorides 9-83 in a triple domino process consisting of amide formation/hetero Diels-Alder reaction and retro-Michael cycloreversion via 9-84 and 9-85 (Scheme 9.17). The pyrrolo[3,4-fc]pyridines can be obtained in even higher yields when the whole sequence is carried out as a four-component synthesis in toluene. Here, 1.5 equiv. NH4C1 must be added for the formation of the now intermediate oxazoles [56b]. 

When forced, reactions with ammonia commonly lead to derivatives of pyrrole or pyridine, e.g., 2-furoic acid at 210r,C gives 2-amino-3-hydroxyri-dine.189 Hydrazine is a better nucleophile and attacks 3-acylfurans in hot ethanol if there is no group to be displaced the ring opens and a pyrazole is formed.190... 

Most of the synthetic approaches toward this ring system utilize N-amino pyridinium salts functionalized at the a-position with a carbonyl group. Thus, the amination of 2-(l,3-dioxolan-2-yl)pyridine with tosyl-hydroxylamine gave 78, whose reaction with urea in the presence of boron trifluoride-acetic acid gave 79, which gave the thermally unstable... 

Interestingly, both the amino and the hydroxy groups can participate in another reaction with a suitable reacting group present in the molecule as shown with the two examples in Scheme 23 <1998T11581>. Finally, it should be mentioned that this N-0 bond reduction is also efficient starting from quaternary ammonium derivatives of hexahydro-isoxazolo[2,3- ]pyridines <1999JOC1932>. 

Another quite common reaction involving nucleophilic attack at a carbon atom of the ring is the hydrolysis of hexahydro-oxazolo[3,4- ]pyridines and tetrahydro-oxazolo[3,4-tf]pyridin-l-ones. This reaction has been known for years and is best performed under acidic conditions, respectively, producing 2-hydroxymethyl-piperidines or pipe-colic acid derivatives in good yields representative examples are collected in Table 9. Ammoniolysis of tetrahydro-oxazolo[3,4-tf]pyridin-l -ones with amino acid derivatives has also been reported and produces substituted pipecolic acid amides in good yields <2003H(61)259>. 

Activated esters of A-alkoxycarbonylamino acids are prepared by two approaches, activation of the acid followed by reaction with the hydroxy compound, and trans-esterification. Most of the products are stable enough to be purified by washing a solution of the ester in an organic solvent with aqueous solutions. A few that are not crystalline are purified by passage through a column of silica. The commonly used method for their preparation is addition of dicyclohexylcarbodiimide to a cold mixture of the reactants in dimethylformamide or ethyl acetate. The first Boc-amino acid nitrophenyl esters were obtained using pyridine as solvent. Pyridine generates the nitrophenoxide ion that is more reactive. For one type of ester, 2-hydroxypyridino... 

The alternative method for making activated esters is base-catalyzed transesterification. Fmoc-amino acids are esterified in excellent yields by reaction with pentafluorophenyl trifluoroacetate at 40°C in the presence of pyridine (Figure 7.13). A mixed anhydride is formed initially, and the anhydride is then attacked by the pentafluorophenoxy anion that is generated by the pyridine. Succinimido, chlorophe-nyl, and nitrophenyl esters were made by this method when it was introduced decades ago. A unique variant of this approach is the use of mixed carbonates that contain an isopropenyl group [Cf C CfyO-COjR]. These react with hydroxy compounds in the presence of triethylamine or 4-dimethylaminopyridine (see Section 4.19) to give the esters and acetone.30 35... 

Di-/m-butyl-4-methy I pyridine (3) is hindered, allows coupling of Fmoc-amino-acid fluorides with weak nucleophiles (see Section 7.12) and is best for minimizing the enantiomerizaton of Fmoc-Cys(tBu)-F (see Section 8.1) during its reaction with the hydroxyl group of a linker-resin. 

Amino-2,3-dimethyl-3//-imidazo[4,5-fc]pyridine was reacted with EMME in boiling toluene for 2 hr to afford 7V-(imidazopyridin-5-yl)amino-methylenemalonate (91) in 84% yield (86EUP174832). The reaction of 3-amino-4,6-dimethyl- l//-pyrazolo[3,4-6]pyridine and EMME yielded N-(4,6- dimethyl -1 //- pyrazolo[3,4 - 6]py ridin- 3 - y l)aminomet hy lenemalonate (92) (87MI5). 

---