Amino-1,5-naphthyridines complexation

The ionization constants,331 NMR spectra,174 and mass spectra1227 of representative amino-1,6-naphthyridines have been compared with those of related amino derivatives. Complexes of l,6-naphthyridin-2-amines with tetracyanoquinodi-methane have been studied.416 4-(3-Dimethylamino-l-methylpropylamino)-l,6-naphthyridine showed significant antimalarial activity.236 X-ray analyses of a number of 5-amino-1,6-naphthyridines have been reported in connection with their antibacterial activities for example, ethyl 5-amino-7-benzylseleno-8-cyano-4-(fur-2-yl)-l,2-dimethyl-l,4-dihydro-l,6-naphthyridine-3-carboxylate (10) proved to be a mixture of two symmetric conformers in each crystal 772 the other related compounds appear to be composed of single conformers.558,560 562 759 781 1289... 

The compounds 87a and 87b are aminated at position 4, yielding the 4-amino compound (88a, 40%) and the 2,4-diamino compound (88b, 11%) respectively the 2-ethoxy compound (87c), however, undergoes amination at position 4 as well at position 5, giving a mixture of the 4-amino compound (88c, 20%) and the 5-amino compound (89a, 14%).Tlie 2-chloro compound (87d) yields a highly complex reaction mixture from which the 5-amino compound (89b), the 2,4-diamino derivative (88b), and 2,5-diamino-l,8-naphthyridine (89c) could be isolated. l-Ethyl-3-nitro-l,8-naphthyridin-2(lH)-one (90a) and 3,6-dinitro-l-ethyl-l,8-naphthyridin-2(lH)-one (90b) were aminated exclusively in the 4-position to give compounds 91a (62%) and 91b (45%), respectively (93LA471). 

The H- and 3C-NMR spectra of a solution of 7 in K.NH2/NH3 measured at — 50 C are complex. It was originally suggested that in this solution a mixture of three a-adducts, 2-amino- (8), 6-amino-, and 8-amino-dihydro-1,7-naphthyridinide (9), was present.15 More detailed studies on covalent animation with 6,8-dideutero-l,7-naphthyridine have shown that this suggestion was not correct the upheld shift value of Af> = 3.12 ppm, originally assigned to H-6 in the 6-amino adduct, must be ascribed to H-5 in 9 (Figure l).16 13C-NMR spectroscopy confirms these results. In fact a mixture of only two adducts, 8 and 9, is formed when 7 is dissolved in KNH2/NH3. 

Ferrarini et al. studied the reaction of 2,6-diamino- and 2-amino-6-acetamidopyridine with different jS-oxo esters in polyphosphoric acid at 80°C (90JHC881). Generally, complex reaction mixtures that contained different bi- and tricyclic products were obtained (see Scheme 7 and Table IX). The products were separated by flash chromatography. In the case of 2-amino-6-acetamidopyridine, the 2,6-diacetamidopyridine 97 was the main product. This compound 97 was also obtained by transamidation in good yield when 2-amino-6-acetamidopyridine was heated in polyphosphoric acid at 80°C. 2-Hydroxy-1,8-naphthyridines 98 were formed in a Conrad-Limpach-type cyclocondensation of 2-aminopyridines and /3-keto ester, while 4-hydroxy-1,8-naphthyridines 99 were probably formed by a ring transformation of 4//-pyrido[l,2-a]pyrimidin-4-ones 100 obtained by the cyclocondensation of 2-aminopyridines and a /3-keto ester. The cyclocondensation of 7-amino-4-hydroxy-l,8-naphthyridine 99 (R = H) and a... 

An ingenious method for the construction of the 1,6-naphthyridine system with the use of chelate methodology was developed (1994IZV1510). Thus, the reaction of 3-acetyl-4-amino-5,5,5-trifluoro-3-penten-2-one 99 with Ph2BOBu afforded a chelate complex, which reacted with primary amines and then with two equivalents of dimethylformamide dimethyl acetal to give 5-trifluoromethyl-l,6-naphthyridin-4(17Z)-ones 100. 

V- 6-[2-(7-methyl[l, 8]naphthyridin-2-yl)ethyl]pyridine-2-yl acetamide 356 was prepared by the reaction of 2,7-dimethyl-l,8-naphthyridines 357 with n-butyllithi-um and 2-/V-acetylamino-6-bromomethylpyridine 358. Another carrier, viz., N-(l-methyl[l,8]naphthyridin-2-yl)-7V -(6-methylpyridin-2-yl)isophtalamide 359, was synthesized from 2-amino-7-methyl-l,8-naphthyridine 360, 2-amino-6-methylpyridine 226a and isophthaloyl chloride 361 in dry dichloromethane in the presence of tri-ethylamine. N,N -bis(l-mcl y [, 8]naphthyridin-2-yl)isophthalamide 362 was prepared from naphthyridines 360 and chloride 361 under analogous conditions. Isophthalamides 359 and 362 were used for the determination of L-( + )tartaric acid as complexes (1 1) soluble in chloroform (1999JIC661, 2001T4987). 

The CG base-pair (i.e., 40 -41, R = ribose) is the prototypical DDA AAD complex (Fig. 5). The AAD (cytosine) array is also found in 2-amidonaphthyri-dines (e.g., 42 and 44). 2-Amino-5,7-dimethyl-l,8-naphthyridine is readily synthesized by the acid-catalyzed reaction of 2,6-diaminopyridine and acetyl-acetone [31] and is commercially available. Subsequent reaction with acetic anhydride readily affords 44. In contrast, the DDA array is less common and less accessible synthetically. This motif is found primarily in the 6-amino-2(lH)-pyridone (43) [17], guanine (41, 47), and 7-deazaguanine (45) [18] chromophores. 

In the another attempt, 1,8-naphthyridines 377 were prepared via 4-aminopyrimidine-5-carboxaldehyde (Figure 17) and used as receptors in complexation studies with several guanidinium and ammonium guests, including derivatives of the amino acids arginine and lysine (02JA14092). 

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