1.8- Naphthyridine-3-carboxylates

Phenacyl-6-aminopenicillate HCI D-Phenylglycyl Chloride HCI 4-Hydro xy-1,5-naphthyridine-3-carboxylic acid-N-succinimide ester... 

When 3-aminopyridine was reacted with EMME in Dowtherm A, first at 150°C for 1 hr and then at boiling temperature for 1 hr, ethyl 4-hydroxy-1,5-naphthyridine-3-carboxylate was obtained in 73-82% yields (46JA-1317). 

The reaction of 5-amino-2-hydroxypyridine and EMME refluxing diphenyl ether for 1 hr gave 4,6-dihydroxy-1,5-naphthyridine-3-carboxylate in 20% yield after vacuum sublimation of the crude product (71JOC1331). 

The cyclization of diethyl N-( l-methyl-4-oxo-1,4-dihydropyrid-3-yl) aminomethylenemalonate by heating in boiling Dowtherm A for 15 min afforded 1,5-naphthyridine-3-carboxylate (982) in 35% yield (78JOC1331). 

Diethoxycarbonylvinyl)amino]-4-methoxypyridine (19) gave ethyl 8-methoxy-4-oxo- 1,4-dihydro-1,5-naphthyridine-3-carboxylate (20) (Ph20,... 

Ethyl 4-oxo-1,4-dihydro-l,5-naphthyridine-3-carboxylate (13, R = H) gave ethyl 4-chloro-l,5-naphthyridine-3-carboxylate (14, R = H) (POCl3 for details, see original) 433 ethyl 6-p-chlorophenoxy-4-oxo-l,4-dihydro-1, 5-naphthyridine-3-carboxylate (13, R = OC,H Cl-p) gave ethyl 4-chloro-6-... 

Ethyl 7-chloro-1 -ethyl-4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxylate (45) gave 1 -ethyl-7-methoxy-4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxylic acid (46) (KOH, MeOH, dibenzo-l,8-crown-6 MeCNJ, reflux, 7h 67% it would seem that the crown ether was required to assist alcoholysis of the unactivated chloro substituent note incidental saponification of the ester group).1398... 

Bromo-1 -ethyl-4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxylic acid (56, R = Br) gave 7-dimethylamino-l-ethyl-4-oxo-1,4-dihydro- (56, R = NMe2) (Me2NH, Me2NCHO, EtOH, CuS04, 110°C, sealed, 5h 20%) or 1-ethyl-4-oxo-7-(pyrrolidin-1 -yl)-1,4-dihydro-1,5-naphthyridine-3 -carboxylic acid [52, R = N(CH2)4] [HN (CH2)4, Me2NCHO, 125°C (reflux), 6 h 44%].1398... 

Bromo-1 -ethyl-4-oxo-1,4-dihydro-l, 5-naphthyridine-3-carboxylic acid gave l-ethyl-7-methylthio-4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxylic acid... 

Ethyl 6-p-chlorophenoxy-4-(3-diethylaminopropyl)amino-1,5-naphthyridine-3-carboxylate (9a, R = C02Et) gave 2-/ -chlorophenoxy-8-(3-diethylaminopro-pyl)amino-7-hydroxymethyl-l,5-naphthyridine (9a, R = CH2OH) 11AIH,-Et20, 10 min substrate/Et2OJ, dropwise then 20°C, 1 h 32%).967... 

Ethyl 7-bromo-4-oxo-l,4-dihydro-l,5-naphthyridine-3-carboxylate (5, Q = H, R = Br) gave 7-bromo-4-oxo-l,4-dihydro-l,5-naphthyridine-3-carboxylic acid (6, Q = H, R = Br) (2.5M NaOH, reflux, 1 h - 85%) 1377 ethyl l-ethyl-7-methyl-4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxylate (5, Q = Et, R = Me) gave l-ethyl-7-methyl-4-oxo-l,4-dihydro-l,5-naphthyridine-3-carboxyhc acid (6, Q - Et, R = Me) (0.7M KOM, reflux, 2.5 h 56% analogs somewhat similarly).1398... 

Butoxy-2-methyl-1,5-naphthyridin-4-amine 2-Butoxy-6-methyl-1,5-naphthyridine 6-Butoxy-2-methyl-l,5-naphthyridin-4(l/7)-one 2-Butoxy-6-methyl-8-phenoxy-l,5-naphthyridine 2-Butoxy-1,5-naphthyridine 6-Butoxy-1,5-naphthyridin-4(l//)-one 6-Butoxy-4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxylic acid... 

Chloro-1 -ethyl-4-oxo-1,4-dihydro-1, 5-naphthyridine-3-carboxylic acid... 

Ethyl 6,7-dimethyl-4-oxo-1,4-dihydro-1, 5-naphthyridine-3-carboxylate 1 -Ethyl-6,7-dimethyl-4-oxo-1,4-dihydro-1, 5-naphthyridine-3-carboxylic acid Ethyl 4,6-dioxo-1,4,5,6-tetrahydro-1, 5-naphthyridine-3-carboxylate Ethyl 4,8-dioxo-1,5,8-tetrahydro-1, 5-naphthyridine-3-carboxylate Ethyl 7-ethoxy-l-ethyl-4-oxo-l,... 

In the above procedure, the use of 4-hydroxy-1,5-naphthyridine-3-carbonyl chloride in place of 4-hydroxy-1,5-naphthyridine-3-carboxylic acid N-succinimide ester can also afford the same objective compound as above. The use of sodium thio-n-propoxide in place of sodium thiophenoxide can also give the objective compound in the form of the sodium salt. 

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