Pyrazolo triazin-7-ones

Treatment of 5-(dichlorophenylmethyl)-3-phenyl[ 1,2,4]triazin-6( 1H)-one 357 or the respective ketone with hydrazine or phenylhydrazine gave 358, which were cyclized with acetic acid to pyrazolo[4,3-c][ 1,2,4]triazines 359 (84PHA504 85MI2) (Scheme 77). 

The inverse electron demand reactions of 2,4,6-tris(ethoxycarbonyl)-1,3,5-triazine and 5-aminopyrazoles to provide a one-step synthesis of pyrazolo[3,4-. 

Pyrazolo[l,5-a][l,3,5]triazines 58 were obtained by an efficient one-step reaction from iminodithiocarbonates 54 and pyrazole 55, or by an alternative two-step reaction form the aroyl isothiocyanates 56 and pyrazole 55 <06TL5441>. 

If, however, the data reported for H-3 in this system is compared to that reported for H-4 in 96, one can realize that relying only on H-NMR for elucidating structures of derivatives of pyrazolo[5,1 -c]-1,2,4-triazines may be misleading (81JHC675). 

Pyrazolo[l,5-a]-l,3,5-triazines are also obtained from acyclic intermediates. Thus, treatment of cyanoethanoic acid hydrazide with benzoyl isothiocyanate affords the corresponding benzoylthiosemicarbazide, which cyclizes into 4-thioxo-2-phenyl-3,4,6,7-tetrahydropyrazolo[l,5-a]-l,3,5-triazine-7-one upon treatment with 5% potassium hydroxide (84JHC781). 

A convienient route to pyrazolo[l,5-t/]-l,2,4-triazines utilizing pyrazol-5-carbohydrazide (128) has been reported (55JA1148). Thus, 128 R = H, afforded pyrazolo[l,5-cTl-l,2,4-triazine (131) on treatment with orthoesters, probably via acyclic intermediate 130. Treatment of 128 with orthoesters afforded mesoionic 129 (Scheme 17) (80JHC1291). Treatment of 4-ribosylpyrazol-5-aldehyde ethoxycarbonylhydrazone with cesium carbonate afforded C-ribosylpyrazolo[l,5-cf -l,2,4-triazin-4-one (83MI1). 

Unlike imidazo[4,5-i/][l,2,3]triazin-4-ones (Scheme 11), the DMAP adduct 20 of pyrazolo[3,4-tf][l,2,3]triazin-4-one is sufficiently stable to be isolated, and treatment with the appropriate amine or ammonium hydroxide gave 4-amines 21 in good yields (Scheme 13) <1995JHC1417>. 

Hydrolysis of the hydrazine BOC-protecting group of 90 followed by treatment with sodium hydride gave pyrazolo[4,3-f][l,2,4]triazine-3-one 44 by nucleophilic cyclization onto the 5-ethoxycarbonyl group (Scheme 64) <2006JA5646>. 

When the synthesis of a heterocyclic system containing a diazole fused onto l,2,3-triazin-4-one (e.g., imidazo[4,5-i [l,2,3]tnazin-4-one (Section 10.13.9.1.l(i)) and pyrazolo[3,4-rf [l,2,3]triazin-4-one (Section 10.13.9.1.1(ii))) or 1,2,3-triazole fused onto pyrimidin-4(7)-(di)one (e.g., [l,2,3]triazolo[4,5-rf pyrimidin-4(7)-(di)one (Section 10.13.9.1.l(iv))) is required, the synthesis of the six-membered ring is the most reliable method. There are several recent accounts of six-membered annulations onto 1,2,3-triazoles to give [l,2,3]triazolo[4,5-r/ pyrimidines (Section 10.13.9.1.l(iv)), which are valuable alternatives to 1,2,3-triazole annulation using nitrosation techniques <1996CHEC-II(7)489>. 

Reactions which can be considered as cycloadditions are rare in the 1,2,3-triazine field. 4-Substituted 1,2,3-benzotriazines (2) react with diphenylcyclopropenone to give one, two or three of the following products pyrazolo[l,2-a][l,2,3]benzotriazin-l-ones (69), pyrazolo[l,2-a][l,2,3]benzotriazin-3-ones (70) or pyrazolo[2,3-a ]quinazolines (71) (80CC808). 

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]

One of the classical methods for the generation of imidoyl azides as precursors to mono- and disubstituted tetrazoles is based on reactions of amidrazoles with sodium nitrite. This procedure developed by Kaufmann et al. in the middle of thel960s <2004SOS(13)861> has found an extension and advancement in recent studies. By this method, 5-hydrazino-3-methyl-l-phenyl-l//-pyrazolo[4,3-< ][l,2,4]triazine 503 through a cyclic imidoyl azide 504 was converted into 5-phcnyl-l //-pyra/olo[4,3-<,]tetrazolo[4,5- tria/inc 505 (Scheme 64) <2005JCX151>. 

Surprisingly, in the systems considered in this chapter, which are related to the purines by inclusion of one more heteratom, no natural products have been found. Only two natural products which fall within the scope of this chapter, the pyrazolo[4,3-e][l, 2,4]triazines (69) and (69a), have been isolated <72CB1949>. These compounds are the fluorescent principle in the monocellular organism, Pseudomonas fluorescens. The yellow pigment is a precursor of the red pigment and the shift in the spectrum is due to the formation of an o-quinonoid structure on methylation. 

---