Pyrrolo -1,8-naphthyridines

Representatives of the pyrrolo[3,2-/][l,7]naphthyridine ring system, viz. 61, have been obtained by palladium-catalyzed cyclization of the corresponding 5-alkenyl-6-amino[l,7]naphthyridines (Scheme 19) <2002H(56)443>, although this reaction appears not to be general and its scope is as yet undefined. 

Under conventional heating the rearrangement [21] of pyrrolo-[2,l-c]-benzodiaze-pine, 45, in boiling phosphorus oxychloride, into benzo-[h][l,6]-naphthyridine 46 required a long reaction time (5 h) (Scheme 8.16). 

Hexahydro pyrrolo-benzdiazepinetrione 394 in boiling phosphorous oxychloride produces 3,5-dichlorobenzo[/z][l,6]naphthyridine 396 as rearrangement product of trichloride 395 (Scheme 81 (2003JHC255)). The suggested mechanism includes thermal aromatization in the final step. 

The preparation and study of tautomers derived from 2-(2 -pyridyl)indole, 2-(2 -pyrrolo)[l,8]naphthyridine, and related heterocycles has been undertaken using ultraviolet (UV) and nuclear magnetic resonance (NMR) spectroscopy and also by molecular orbital (MO) calculations <1998JOC4055>. 

All four pyrrolo[2,3]pyridines can be prepared by photochemical ring contraction of naphthyridine derivatives, e.g. (210). Although reliable, multistep syntheses are needed for the photolysis substrates, which can only be irradiated in small quantities (Scheme 67) <58LA(612)153>. 

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]

Butyl-5-formylmethyl-l,7-naphthyridin-6-amine (7) underwent intramolecular cyclization to give 5-butyl-3//-pyrrolo[3,2-/] 1,7 naphthyridine (8) (acidic conditions 72% no details).132... 

Amino-l,7-naphthyridin-4(l//)-one (10) underwent diazotization to give 4-oxo-3,4-dihydro-l,7-naphthyridin-3-ylidendiazonium chloride hydrochloride (11) (NaN02, HC1, 0°C 80%) and subsequent ring contraction on irradiation to afford pyrrolo[2,3-c]pyridine-3-carboxylic acid (12) (AcOH, H20, hv,... 

Pyrrolo 2,3-/ Ipyridine (75) underwent pyrolysis in chloroform to give a separable mixture of 1,8-naphthyridine (76, R=H) and 3-chloro-l,8-naphthyridine (76, R=C1) (vapor phase, 550°C low yields).1145... 

Methoxycarbonyl methyl-1 //-pyrrolo 3,4-r pyridine-l,3(2//)-dione (47) has been reported to undergo ring expansion to afford methyl 4-hydroxy-1-oxo-l,2-dihydro-2,7-naphthyridine-3-carboxylate (48) (MeONa/MeOH, 100°C ... 

Scheme 59 Cl-cycloaddition-elimination three-component synthesis of pyrrolo(2,3- )p5 dines 109, 1,8-naphthyridines 110, and pyrido(2,3-i>)azepines 111...

Schramm nee Dediu OG, Oeser T, Muller TJJ (2006) Coupling-isomerization-iV,5-ketene acetal-addition sequences - a three-component approach to highly fluorescent pyrrolo[2,3-h] pyridines, [l,8]naphthyridines, and pyrido[2,3-b]azepines. J Org Chem 71 3494—3500 Wiesner J, Ortmann R, Jomaa H, Schlitzer M (2003) New Antimalarial Drags. Angew Chem... 

A series of 1-substituted and 1,4-disubstituted 2,6-naphthyridines were prepared by base-mediated intramolecular cyclization of pyrrolo[2,3-c][2,6]naphthyridines by palladium catalyzed amination (2003A40). 

Most of the compounds reported in this chapter are the naphthyridines fused with a five-membered ring containing one heteroatom, i.e. pyrrolo-, furo- and thienonaphthyridine compounds. Some other ring systems, which are the few known examples of the numerous possible structures, have only been studied sparsely and they will be presented briefly in Section 8.37.2.8. 

No systematic studies of UV and IR spectra of the parent tricyclic rings have appeared in literature. UV Spectra data of some l/f-pyrrolo[3,2-c][l,8]naphthyridine (38), ll/f-indolo[3,2-c] [l,8]naphthyridine (39) and 10/f-indolo[2,3- >]naphthyridine (40) derivatives is listed in Table 4. 

Af-Aroyl derivatives of a-aminonicotyrine (99) underwent the Bischler-Napieralski cyclization reaction to give l/f-pyrrolo[3,2-c][l,8]naphthyridine products (38) in excellent yield, the first example of the preparation of pyrrolonaphthyridine compounds being reported in 1960 (Equation (26)) <60JCS1509>. 

Most of the compounds are named on the basis of indolizine and quinolizine nuclei with the exception of pyrrolo[l,2]naphthyridines, i.e. indolizine fused to a pyridine ring. In practice, two systems are used for numbering indolo[2,3-a]quinolizine examples shown below are indolo[2,3-ajquinolizine which is numbered according to the lUPAC recommendations also used in Chemical Abstracts, and tetrahydroindolo[2,3-a]benzo[9]quinolizine numbered following the generally accepted biogenetic numbering system. 

The synthesis of pyrrolonaphthyridine derivatives has been reported from 1,3-dipolar cycloaddition reaction of naphthyridinium dicyanomethylides with DMAD. Starting from [1,5]- and [1,8]-naphthyridines (139), dicyanomethylides (140) were prepared on treatment with tetracyanoethylene oxide (TCNEO) in THE and they underwent 1,3-cycloaddition with DMAD in acetonitrile to afford aromatic products (142) after elimination of HCN from the adducts (141) (Scheme 18). Pyrrolo[2,l-/]naphthyridine (143) was obtained when the N-6 dieyanomethylide of [l,6]-naphthyridinium was employed <93H(36)1945>. 

A fully conjugated ring system, pyrrolo[l,2-a][l,8]naphthyridine (170), has been constructed by refluxing 3-[2-(l-pyrrolyl)pyridyl]acetic acid (169) in acetic anhydride (Scheme 25). An alternative... 

Rearrangement of pyrrolo[2,l-c][l,4]benzodiazepine-5,ll-diones 332 (n— 1) and pyrido[2,l-c][l,4]benzodiazepine-6,12-diones 333 ( = 2) into 5-chloro-l,2,3,4-tetrahy-dro-benzo[/i][l, 6]naphthyridine 334 and 6-chloro-2,3,4,5-tetrahydro-l/7-azepino... 

N-Heterocychc scaffolds such as indolo[2,l-ii]isoquinohnes, pyrrolo[2,l-a] isoquinolines, and indolo/pyrrolo[2,l [l,6]naphthyridines are abundant in natural products and biologically active scaffolds, semiconductors, and luminescent materials. Verma and coworkers have described a rapid high yield synthesis of medicinally important indolo-, pyrrolo[2,l [l,6]naph-thyridines, and isoquinolines 89 via a copper-catalyzed tandem approach (2014TL(55)4724). This microwave-assisted protocol uses hydroxymethyl... 

Scheme 24 Synthesis of indolo-, pyrrolo[2,1-/][1,6]naphthyridines, and isoquinolines 89.

A new heterocyclic ring system, pyrrolo(3,2-3,4]-l,8-naphthyridine (IX-121) is obtained from the cyclization of mono- and diW-acyl derivatives of 2-aminonicotyrine (IX-120) with phosphoms oxychloride. Thus, 2-dibenzoyl-aminonicotyrine is dissolved in toluene and phosphorus oxychloride and heated... 

The asymmetric 3 + 2-cycloaddition of cyclic azomethine ylides with Oppolzer s acryloyl camphor sultam has been used for the construction of X-azabicyclo[7M.2.1] alkenes in optically pure form. The non-stereospeciflc 1,3-dipolar cycloaddition of electron-poor azomethine ylides and electron-rich enamines proceeds by a two-step mechanism via zwitterionic intermediates. The 1,3-dipolar cycloaddition of 4,6-diazaphenanthrene 6-phenacylide with a variety of dienophiles readily produces the fused heterocycles tetrahydrobenzo[/]pyrrolo[l,2-/z][l,7]naphthyridines. Sequential... 

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