2-Amino-5,7-dimethyl-1,8-naphthyridine

Naphth[2,l-d]oxazolium iodide, 2,3-dimethyl-reactions, 6, 215 Naphthyridine, amino-reactions, 2, 598 Naphthyridine, N-amino-reactions, 2, 596 Naphthyridine, 3-bromo-reactions... 

Oxidation of the 2-(S,S-dimethyl)sulhnylimine derivatives (74) of 2-amino-l,X-naphthyridines (73a-73c) (X = 5,6,8) with m-chloroperbenzoic... 

Chemical Name 6-[ [ [ [(4-Hydroxy-1,5-naphthyridin-3-yl)carbonyl] amino] -phenyl acetyl] -amino] -3,3-dimethyl-7-oxo4-thia-1 -atabicydo[3.2.0] -heptane-2-carboxylic acid... 

The reaction of 2-amino-5,7-dimethyl-1,8-naphthyridine and EMME in boiling Dowtherm A for 45 min gave the pyrido[l,2-o]-1,8-naphthyridine derivative (1602) in 40% yield. The same product (1602) was obtained in 44% yield in the reaction of N-( 1,8-naphthyridin-2-yl)aminomethylene-malonate (1603) and EMME in boiling Dowtherm A for 1 hr. The thermal ring closure of 1603 was unsuccessful. An ethanolic suspension of 1603 was treated with concentrated aqueous ammonium hydroxide at reflux for 24 hr to give 2-aminopyrido[ 1,2-a]-1,8-naphthyridine (1604) in quantitative yield (80FES1052). 

The reaction of 7-amino-6-carbethoxy-3-cyano-l,4-dimethyl[l,8]naphthyridin-2(17/)-one with piperidine or morpholine does not afford the corresponding substituted [l,8]naphthyridin-2-ones but instead leads to thermal decomposition to give 6-amino-3-cyano-l,4-dimethylpyridin-2(l//)-one (Scheme 6) <2001S103>. 

Okuda condensed 4-amino-2,6-lutidine with EMME and converted the resulting hydroxy ester into 5,7-dimethyl-l,6-naphthyridine.86... 

The amino moiety of the 3-carbohydrazide group of unsaturated and 6,7,8,9-tetrahydro-4-oxo-47/-pyrido[l,2-n]pyrimidine-3-carbohydrazides was condensed with acetone and 5-nitro-2-furoaldehyde (830MR687 88EUP252809). The reaction of 6-methyl-6,7,8,9-tetrahydro-4-oxo-4//-pyrido[l,2-a]pyrimidine-3-carbohydrazide with diethyl 2-[2-dimethyl-amino)vinyl]-6-methylpyridine-3,5-dicarboxylate in boiling ethanol for 4 hours afforded N-( 1,6-naphthyridin-6-yl)-4-oxo-4//-pyrido[ 1,2-a]pyrimi-dine-3-carboxamide 426 (85MIP1). 

Ring transformation of the initial 6-substituted 4//-pyrido[l,2-a] pyrimidin-4-ones also occurred when 2-[(6-substituted 2-pyridyl)acrylates were heated in a high-boiling solvent. For example, heating diethyl [(4,6-dimethyl-2-pyridyl)amino]malonate in boiling diphenyl ether afforded ethyl 5,7-dimethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate... 

Diethoxycarbonylvinyl)amino]-5,6-dimethylpyridine (17) underwent regioselective thermal cyclization to give ethyl 6,7-dimethyl-4-oxo-l,4-dihy-dro-l,5-naphthyridine-3-carboxylate (18) (Dowtherm A, reflux, 15 min 89% analogs likewise).1398... 

Dicyanomethyl)-4,6-dimethyl-3-pyridinecarbonitrile (44) gave 5-amino-7-methoxy-2,4-dimethyl-l,6-naphthyridine-8-carbonitrile (45) (MeONa, MeOH, reflux, 12 h 16%), 994 cf- g95,9i3,930... 

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... 

Note Only a typical example is given here. Crude 5-amino-7-hydrazino-2,4-dimethyl-l,6-naphthyridine-8-carbonitrile (28) gave 2,4-dimethyl-7//-pyrazolo-[3,4-h [l,6]naphthyridine-2,9-diamine (29) (EtOH, reflux, 6 h 72%) analogs likewise.895... 

Acetyl-l-methylethylidene)amino-2-pyridinamine (19) gave 5,7-dimethyl-l,8-naphthyridin-2-amine (20) (H3P04, 100°C 84%).104... 

Methyl-2-pyridinamine (45, R=Me) with diethyl (l-ethoxyethylidene)malo-nate gave ethyl 2,7-dimethyl-4-oxo-1,4-dihydro-l,8-naphthyridine-3-carbox-ylate (46) (Dowtherm, 240°C 22%) 249 2-pyridinamine (45, R H) with diethyl malonate gave 4-hydroxy-l,8-naphthyridin-2(lfl)-one (47) (neat reactants, heat 85 %) 693 and 2,6-pyridinediamine (45, R=NH2) with malic acid gave 7-amino-1,8-naphthyridin-2(l//)-one (48) (H2SO4, heat 85-97%) 389>681>1018... 

Ethyl 2-amino-6-cyano- with triethyl orthoformate gave ethyl 6-cyano-2-(ethoxymethyleneamino)-5,8-dimethyl-7-oxo-7,8-dihydro-l,8-naphthyridine-3-carboxylate (29) (neat reactants, reflux 73%).618... 

Benzoyl-iV-ethyl-1 -methylthiovinylamine (4) with 2-cyano-A -methylaceta-mide (2 mol) gave l-amino-2,7-dimethyl-3,8-dioxo-6-phenyl-2,3,7,8-tetrahy-dro-2,7-naphthyridine-4-carbonitrile (5) (reactants, Pr ONa, Pr OH, reflux 75% analogs likewise).699... 

A possible example of direct C-imination has been described a substrate, formulated as l-amino-8-imino-2,7-diphenyl-5,8-dihydro-2,7-naphthyridine-3,6(2//,7//)-dione (80), was reported to condense with A,A-dimethyl-p-nitrosoaniline to give 1 -amino-5-p-dimethylaminophenylimino-8-imino-2, 7-diphenyl-5,8-dihydro-2,7-naphthyridine-3,6(277,777)-dione (81) (reactants, trace piperidine, EtOH, reflux 55%) 802 an isomeric azo compound might have been expected. 

Amino-iV-ethyl-1,6-naphthyridine-3-carboxamide 5-Amino-7-hydrazino-2,4-dimethyl-1, 6-naphthyridine-8-carbonitrile 5-Amino-7-hydrazino-2,4-diphenyl-1, 6-naphthyridine-8-carbonitrile 5-Amino-7-hydrazino-2-phenyl-1,6-naphthyridine-8-carbonitrile... 

Amino-1,4-dimethyl-1,8-naphthyridin-2(l/7)-one 7-Ami no-2,3-dimethyl-l,8-naphthyridin-4(l//)-one 2-Ami no-5,7-dimethy 1-4-oxo-1,4-dihydro-1,... 

Ethyl 2-amino-5,7-dimethyl-4-oxo-l, 4-dihydro-1,8-naphthyridine-3-carboxylate 366 1301... 

Methyl 7-acetamido-4-oxo-1,4-dihydro-1,8-naphthyridine-2-carboxylate Methyl l-acetyl-4-hydroxy-2-oxo-l,2-dihydro-1,8-naphthyridine-3-carboxylate Methyl 2-amino-5,7-dimethyl-1,8-naphthyridine-... 

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