3-Amino-2-ethoxy-1,5-naphthyridine

In all 3-nitronaphthyridines with an unsubstituted C-2 position (84a, 84f, and 84j) no traces of the corresponding 2-amino-3-nitro-l,X-naphthyridines (X = 5, 6, and 8) were obtained. As already mentioned, in the aminations of 2-R-3-nitronaphthyridines where R is a chloro or ethoxy group, no amino-dechlorination or amino-deethoxylation was observed. 

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). 

Catalytic hydrogenation (Pd/C) of 2-chloro-3-nitro-l,5-naphthyridine (125, R = Cl) in methanolic solution afforded 3-amino-l,5-naphthyridine (126, R = H, 74%) isolated in the form of its trihydrochloride (40MI1). Similar Pd/C hydrogenation of 2-ethoxy-3-nitro-l,5-naphthyridine (125, R = OEt) gave 3-amino-2-ethoxy-l,5-naphthyridine (126, R = OEt, 47%) (80RTC83). Reduction with tin(II) chloride in hydrochloric acid also leads to 126, (R = OEt, 73%) (63RTC997). 

The Friedlander condensation of 2,6-diaminopyridine-3,5-dicarbaldehyde (393) with various ketones has been reported (77JOC3410). Reaction of the aldehyde with acetophenone, with deoxybenzoin and with a-tetralone generates the 5,10-dihydro-l,9,10-anthyridine derivatives (394 R = H), (394 R = Ph) and (395) respectively, whilst with acenaphthenone the nonacyclic anthyridine (396) is obtained. The condensation between 2-amino-3-ethoxy-carbonyI-l,8-naphthyridine (225) and alkyl carboxylates under basic conditions produces 4-hydroxy-1,9,10-anthyridin-2-ones (397) (79BAP571). 

Ethoxy-3-nitro-l,8-naphthyridine (41c) 4-Amino-2-eihoxy-3-nitro-... 

It has been reported that 3-bromo-2-ethoxy-l,5-naphthyridine (71) with potassium amide gives as sole product the unrearranged 3-amino-2-ethoxy-... 

Ethyl 7-ethoxy-l-ethyl-6-nitro- (9, R = N02) gave ethyl 6-amino-7-ethoxy-l-ethyl-4-oxo-1,4-dihydro-l,8-naphthyridine-3-carboxylate (9, R = NH2) (Fe powder, AcOH 85°C 94%).1211... 

Ethoxy-1,6-naphthyridine 2-Ethoxy-3-nitro-l,6-naphthyridin-4-amine 2- Ethoxy-3-nitro- 1,6-naphthyridine Ethyl 5-amino-7-benzylseleno-8-cyano-2-methyl-1,6-naphthyridine-3-carboxylate Ethyl 6-amino-2-methyl-5-oxo-5,... 

Ethyl 2-amino-6-cyano-7-ethoxy- 5-phenyl-l,8-naphthyridine-3-carboxylate 293-295, IR, MS, NMR 896... 

Ethyl 6-amino-7-ethoxy- l-ethyl-4-oxo-1, 4-dihydro-l,8-naphthyridine-3-carboxylate 249-253, IR 1211... 

A solution of 2-chloro- and 2-amino-3,5-dinitro-l,8-naphthyridine in liquid ammonia shows the presence of a covalent adduct at C-4, as proved by NMR spectroscopy (83RTC359, 83RTC511, 83JHC9, 85JHC761, 93LAC 471, 00AHC(77)285). The NMR spectrum of a solution of 2-ethoxy-3,5-dinitro-l,8-naphthyridine and 2-chloro-3,5-dinitro-l,8-naphthyridine in liquid ammonia features the presence of two covalent adducts one at C-4 as well as one at C-5. The C-4/C-5 adduct ratio is found to be temperature dependent. For the 2-chloro compound the adduct ratio C-4/C-5 is 60/40 at —45°C, but changes to 40/60 at room temperature. This temperature dependency for the 2-ethoxy compound is more pronounced the C-4/C-5 adduct ratio is 50/50 at —45°C and 85/15 at room temperature. 

A mixture of 3-amino-2,6-dimethylpyridine (IX-l 17) and diethyl ethoxy-methylenemalonate when heated on a steam bath under reduced pressure gives diethyl (2,6-dimethyl-3-pyridyl) methylenemalonate (IX-l 18). The latter yields ethyl 4-hydroxy-6,8-dimethyl-l,7-naphthyridine-3-carboxylate (DC-119) when boiled for 4 minutes in diethyl phthalate. 

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