Pyrazolo pyrido

Applications of MCR-Derived Heterocycles in Drug Discovery Table 6 Antibacterial activities of select pyrazolo-pyrido-pyrimidine-diones... 

Treatment of pyrazolo[l,5-a]quinoline-3,3,4-tricarboxylates 79 with CS2CO3 afforded 2,3-dihydro-l//,7//-pyrido[3,2,l-i/]cinnoline-3,3,8-tricar-boxylates 80 (96BCJ1371). 

The pyrimidines 62 undergo cyclisation on refluxing in dioxane to yield not only the pyrazolopyrimidines 63, but the novel pyrazolo[3, 4 4,5]pyrido[2,3-rflpyrimidines 64 by an intramolecular 1,3-dipolar cycloaddition reaction (Scheme 9)<96JCS(P1)1999>. 

Pyrazolo[3,2-c]pyrido[4,3- ][l,2,4]triazine oxides704 were prepared by cyclization of the hydrazone derivatives 703 with ethanolic sodium hydroxide. Subsequent reduction of 704 gave 705 (76JPR835). Hydrazone 703 was prepared by condensation of 4-hydrazino-3-nitropyridine with 702. The mass spectral fragmentation patterns for 704 and 705 and their benzo analogues were studied (77ZC142). 

Alkylation of 2-(pyrazol-l -yl)pyridine 706 with 1,2-dibromoethane afforded (81JHC9) pyrazolo[r,2 -a]pyrido[2,l-c][l,2,4]triazinedium dibromide 707. 

Aminopyrazolo[3,4-6]pyridine was reacted with EMME in acetic acid to give pyrido[2, 3 3,4]pyrazolo[ 1,5-a ]pyrimidine-3,9-dicarboxylate... 

Besides uracil-6-iminophosphorane, the iminophosphorane component was extended to pyrazole 3 and pyrazolon-4-iminophosphoranes 363 (94JOC3985). In its electron distribution, 363 can be compared with uracil 346. With arylisocyanates, pyridine, or y-picoline, zwitterionic pyrazolo [3, 4 4,5]pyrido[6,l-a]pyrimidines (364) are obtained and with isoquinoline, 365 is formed (Scheme 131). Again, both systems show a typical negative solvatochromism (94JOC3985). 

Furthermore, pyrazole 366 reacts with phthalazine (Scheme 132) to afford pyrazolo[3, 4 4,5]pyrido[6,l-a]phthalazine (367). From a mechanistic viewpoint, no 1,6-dipolar cyclization occurs. Instead, an intramolecular nucleophilic aromatic substitution to the heteroarene is likely. Isoquinoline leads to zwitterionic 368 (94JOC3985). 

The presence or absence of the dioxolane protecting group in dienes dictates whether they participate in normal or inverse-electron-demand Diels-Alder reactions.257 The intramolecular inverse-electron-demand Diels-Alder cycloaddition of 1,2,4-triazines tethered with imidazoles produce tetrahydro-l,5-naphthyridines following the loss of N2 and CH3CN.258 The inverse-electron-demand Diels-Alder reaction of 4,6-dinitrobenzofuroxan (137) with ethyl vinyl ether yields two diastereoisomeric dihydrooxazine /V-oxide adducts (138) and (139) together with a bis(dihydrooxazine A -oxide) product (140) in die presence of excess ethyl vinyl ether (Scheme 52).259 The inverse-electron-demand Diels-Alder reaction of 2,4,6-tris(ethoxycarbonyl)-l,3,5-triazine with 5-aminopyrazoles provides a one-step synthesis of pyrazolo[3,4-djpyrimidines.260 The intermolecular inverse-electron-demand Diels-Alder reactions of trialkyl l,2,4-triazine-4,5,6-tricarboxylates with protected 2-aminoimidazole produced li/-imidazo[4,5-c]pyridines and die rearranged 3//-pyrido[3,2-[Pg.460]

A two-step synthesis of pyrazolo[4, 3 5,6]pyrido[2,3-b][l,5]benzothia-zepine (140) has been described (82JHC809) The condensation of 5 with 6-chloro-5-formylpyrazolo[3,4-b]pyridine (138) afforded the benzothiazoline derivative (139), which was then cyclized by refluxing in ethanolic sodium ethoxide to give 140 (Scheme 43). Spectroscopic data of compound 140 are also given. 

Lindsley and co-workers developed a general procedure towards the collection of diverse heterocyclic scaffolds from common 1,2-diketone intermediates 96. Substituted quinoxalines 97, fused pyrazolo [ 4,5-g ] quinoxalines 98 and imidazolo[3,4-g]quinoxalines 99 as well as pyrido[2,3-fo]pyrazines 100 and Ihicno[3,4-fo Ipyrazincs 101 have been prepared in excellent yields [132] (Scheme 54), employing optimized reaction conditions (microwave heating of equimolar mixtures of 1,2-diketone 96 and diamine components at 160 °C for 5 min in 9 1 MeOH - AcOH). The use of microwave irradiation resulted in reduced reaction times (5 min vs. 2-12 hours), improved yields as well as the suppressed formation of polymeric species a characteristic of traditional... 

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