3- Amino-l,8-naphthyridine

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 Skraup reaction, in all of its modifications, has proved to be unsuccessful as a method of obtaining anthyridines. Thus when 2-amino-l,8-naphthyridine (112 R = H) and 3-amino-l,5-naphthyridine (127) are subjected to the modified Skraup reaction using sulfo-mix the products are either triazaphenanthrenes or naphthyridine by-products (75MI21103). Similarly 3,5-diaminopyridine (126) gives 1,5,9-triazaphenanthrene (129) as the only tricyclic product (see Section 2.11.5.3) (67MI21102). 

Amino-l,5-naphthyridin-4 (1 //)-one (21) underwent diazotization to 3-diazo-nio-l,5-naphthyridin-4(1//)-one chloride (22) (substrate, Me2NCHO, 0°C, Me2CHCH2CH2ONO [, HCI/btOH [ 75%), which on irradiation gave 177-pyrrolo[3,2-b]pyridine-3-carboxylic acid hydrochloride (23) [substrate, AcOH, H20, 0°C, hv (arc lamp), h %].722... 

Amino-l,5-naphthyridin-4 (1 //)-one gave crude 3-diazonio-l,6-naphthyridin-4(l//)-one chloride (HC1, NaN02, 5°C, 12 h) and thence 3-diazonio-l,6-naphthyridin-4-olate (26) (NaHC03, Et20 70% overall) 726 subsequent irradiation caused ring contraction to pyrrolo [3,2-[Pg.133]

Various substituted 3-aminopyridines have been cyclized to 1,5-naphthyri-dines. jhree products, IX-104 to IX-106, have been isolated from the Skraup reaction with 3,5-diaminopyridine Czuba has suggested that 3-amino-l,5-naphthyridine (IX-104) was the logical precursor to IX-105 and... 

A low-temperature nitration of 2-amino-l,8-naphthyridine (59a) and 2-amino-l,5-naphthyridine (59b) yielded the 2-nitramino-l,8-naphthyridine (60a, 65%) (98MI3) and 2-nitramino-l,5-naphthyridine (60b, 70%) (63RTC988) respectively. Attempts to rearrange (60a) and (60b) to 2-amino-3- (or 6-) nitro-l,8-(or -1,5-) naphthyridines failed. 

Amino-l,6-naphthyridin-4-one (148), upon irradiation with UV light in the presence of sodium nitrite loses nitrogen to afford the 3-carboxy-5-azaindole (149).85,158 This reaction has also been carried out on the corresponding derivatives of 1,7-naphthyridine158 159 and 7-carboxy-l,8-naphthyridine85 to give the expected 1,6- and 1,7-azaindoles. 

These results combined with those obtained in the aminations of the 3-halogenoquinolines (Section III,B,1) show that 3,4-didehydro-1,5-naphthyri-dine (68) is an intermediate and that 2,3-didehydro-l,5-naphthyridine does not occur, because if it had, then 2-amino- 1,5-naphthyridine should have been formed. 4-Bromo-1,5-naphthyridine (70) also gives a mixture of 69 and 49. The ratio is 77 23, which indicates that the 4-bromo compound (70) undergoes SN(AE),pso aminodebromination to 4922 in addition to an SN(EA) process via 68, yielding 49 as well as 69. 

Reaction of 2-bromo-l,5-naphthyridine (17) with KNH2/NH3 gives,22 in addition to 2-amino-l,5-naphthyridine (48 77%) formed via 149, 4-amino-1,5-naphthyridine (49 1%) and product C8H8N4, which was later proved to be 4-amino-2-methyl-1,3,5-triazanaphthalene (151 11%).23 The ring transformation of 17 into 151 is explained by the intermediary formation of C-4... 

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