Methoxy-6-amino-8-quinoline

One sometimes observes alternating (serrated) variations of activity (zig-zag curves) according to whether the number of atoms of carbon is even or odd. Such an example is found for antimalarials derived from methoxy-6-amino-8-quinoline (Figure 14.14). 

FIGURE 14.14 Antimalarial activity in a homologous series of bifunctional methoxy-6-amino-8-quinolines. Source After Magidson and Strukov. ... 

GFP hopo ICBP IP3 Ln3+ mal memal MLCK nota oxine par pdta pmea py quin-2 green fluorescent protein hydroxypyridinon(at)e intestinal calcium-binding protein inositol 1,4,5-triphosphate a lanthanide(III) cation malonate methylmalonate myosin light chain kinase 1,4,7-triazacyclononane-l,4,7-triacetate 8- hydroxyquinoline pyridine-2-azo-4 -dimethylaniline propylene-1,2-diaminetetraacetate 9- [2-(phosphonomethoxy)ethyl] adenine pjrridine pjrridyl 8-amino-2- [(2-amino-5-methylphenoxy )methyl] -6-methoxyquinoline-ATJV -tetraacetate 2- [ [2-[his(carboxymethyl)amino]-5-methyl-phenoxy] methyl] -6-methoxy-8- [bis(carboxymethyl) amino] quinoline]... 

Methoxyquinoline reacts with a large excess of chlorosulfonic acid (10 equivalents) at 0-15 °C to give the 5-sulfonyl chloride. 8-Methoxy-5-quinoline-sulfonyl chloride is used as an analytical fluorogenic reagent for the chromatographic determination of amines, amino acids and peptides. ... 

Quinoline, amino-2-hydroxy-4-methyl-azo pigments from, 1, 334 Quinoline, 8-amino-6-methoxy-as antimalarial, 2, 517 Quinoline, 4-amino-2-methyl-protonation, 2, 341 Quinoline, anilino-3-substituted... 

N4-(6-methoxy-8-quinolinyl)-1,4-pentanediamine diphosphate. N4-(6-methoxy-8-quinolinyl)-1,4-diaminopentane diphosphate. (RS)-8-(4-amino-l-methylbutylamino)-6-methoxy quinoline diphosphate. 

The thermal cyclization of [(3-chloro-4-fluorophenyl)amino][4-methoxy-phenyl)methylthio]methylenemalonate (789, R = Cl, R1 = 4-MeOC6H4) in diphenyl ether at 250°C for 3 min gave 2-substituted quinoline-3-carbox-ylate (790, R = Cl, R = 4-MeOC6H4) in 66% yield (82EUP58392). 

Nucleophilic substitution with heteroaryl halides is a particularly useful and important reaction. Due to higher reactivity of heteroaryl halides (e.g. 35, equation 24) in nucleophilic substitution these reactions are widely employed for synthesis of Al-heteroaryl hydroxylamines such as 36. Nucleophilic substitution of halogen or sulfonate functions has been performed at positions 2 and 4 of pyridine , quinoline, pyrimidine , pyridazine, pyrazine, purine and 1,3,5-triazine systems. In highly activated positions nucleophilic substitutions of other than halogen functional groups such as amino or methoxy are also common. 

Methoxy-3-isobutylpyrazine 176 (Structure 4.53) is found in galbanum oil obtained from Ferula galbaniflua. 2,4-disubstituted pyridines 177, N,N-dimeth-ylated amino compounds 178, alkyl pyrazines 179, quinoline 180 and methyl quinolines 181 were isolated from fig leaf absolute [64]. 

A few extensions of the Conrad-Limpach synthesis have been applied to the synthesis of 4,7-phenanthrolines. Unlike o-phenylenediamine, which gives a quinoxaline derivative, p-phenylenediamine reacts with excess of ethyl ethoxalylpropionate to give an intermediate bisanil, which cyclizes in hot diphenyl ether to afford 3,8-dicarboethoxy-l,10-dihydroxy-2,9-dimethyl-4,7-phenanthroline in high yield.237 With diethyl ethoxymethylenemalonate as condensing agent, 6-amino-8-methoxy-quinoline has been converted into 2-carboethoxy-l-hydroxy-6-methoxy-4,7-phenanthroline.238 A related condensation affording 1-... 

Halogen atoms in pyrones and pyridones e.g. 902) are unreactive toward SAE nucleophilic displacement. 3-Halopyridines are less reactive than the a- and 7-isomers but distinctly more reactive than unactivated phenyl halides. Thus, a bromine atom in the 3-position of pyridine or quinoline can be replaced by methoxy (NaOMe-MeOH, 150°C), amino (NH3-H20-CuS04, 160°C) or cyano (CuCN, 165°C). 5-Halogens in pyrimidines are also relatively unreactive. 

Methoxy-2,3,4,4fl,5,6-hexahydro-lH-pyrazino[l,2-fl]quinoline was prepared by the cyclization of 8-methoxy-2-[(2-hydroxyethyl)amino-methyl]-l,2,3,4-tetrahydroquinoline, on the action of P205 in boiling xylene overnight (07MIP2). 

Substituent effects follow the general pattern of substituted benzene derivatives in that nitro, sulfonic acid, and carboxyalkyl groups deactivate the ring to further substitution, whereas amino and methoxy groups strongly activate, and methyl and chloro groups have little effect. Ridd383 has recently reviewed electrophilic substitutions on quinoline, pyridine, and imidazole. 

A mixture of 6-bromo-4-(tri luoromethanesulfonyloxy)-5,8-dimethoxy-quinoline (1.35 g, 3.25 mmol), trimethyl[2-[(l,l-dimethylethoxycarbonyl)-amino]phenyl]tin (1.68 g, 4.70 mmol), lithium chloride (330 mg, 7.80 mmol), copper(I) bromide (25 mg, 0.17 mmol), and tetrakis(triphenylphosphine)palla-dium (0) (180 mg, 0.16 mmol) in dioxane (60 cm ) was heated at 90 °C for 60 h. After being cooled to rt, the mixture was partitioned between EtOAc and a 5 % aqueous ethylenediamine solution to remove any copper species, completely. After the usual work up, the residue was chromatographed (1.5 1 hexanes -EtOAc) to yield the title compound as a white solid (952 mg, 64%, several other fractions contained the title compound contaminated with 6-bromo-5,8-di-methoxy-4-methylquinoline) mp 166-168 °C. 

N-Ethoxy- E16a, 219 (O-Alkylier.) 2-(2-Hydroxy-ethyl)- XI/2, 314 Propinsaure 2-Amino-5-methoxy-E9a, 695 (N02 - NH2) Quinolin-l-oxid 2,4-Dihydroxy-3-methyl- E7a, 504 [2-NOz—Ar— CO-CH(CH3)-CHO + Boranat Pd —C]... 

Quinolin 3-Amino-2,4-dihydroxy-6-methoxy- E7a, 402 [4-COOR — 5-(2-acylamino — Ar) — 1,3-oxazol/ HC1]... 

Quinolin 4-(2-Hydroxy-ethyl)-1,2,3,4-tetrahydro- XI/1, 729 Tetralin 5-Amino-6-methoxy- XI/1, 690... 

Pyrazin 2-(bzw. 4)-(4-Methyl-anilinocarbonyl)- E5, 1017 (N3 -v CO-NH-Ar) Pyridazine 4-Cyan-6-hydroxy-5-methyl-3-phenyl-4,5-dihydro-E9a, 570 (4-Oxo -4-Ar-3-CN-2-CH3 —butanoic Acid + N2H4) Pyridin 2-Methoxy-5-phenylazo-E16d, 57 (R-NH2 + R-NO) Pyrrol 2-Amino-3-cyan-1 -(4-methyl-phenyl)- 5-oxo-4,5-dihydro-E15/2, 1946 (Cl-CH2-CO-NR2 + NC-CH2-CN) Quinolin... 

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