Imidazo triazin-4-ones

Imidazo[l,5-t/)[l, 2,4]triazin-l(2//)-ones 504 were prepared (78-USP4115572 79JHC277 88USP4743586) by the cyclization of hydrazide 503 with triethyl orthoesters. l,2,3,4-Tetrahydro-2,4,4-trimethyl-8-nitroimidazo[ 1,5-t/J[ 1,2,4]triazin-1 -one 506 was isolated as a byproduct during the course of purification of hydrazide 505, whose structure was determined (91MI4) by crystal structure analysis. They had antiasthmatic... 

The thermal degradation of 3-(phenylmethyl)pyrido[3,4-e][l, 2,4]triazine gave a large number of compounds, but only 3-(phenylmethyl)pyrido[3,4-e][l, 2,4]triazin-5(6f/)-one and 3-phenyl-l-(phenylmethyl)imidazo[3,4-b]pyrido[3,4-e][l,2,4]triazine were identified (82JHC1533). 

Several methods for the functionalization of the 4-position of imidazo[4,5-d] [ 1,2,3]triazin-4-one to afford 9-ribofuranosyl derivatives of 2-azapurines have been investigated... 

Eschenmoser and co-workers <20030L2067, 20040L3691, 2005HCA1960> carried out thorough synthetic studies for preparation of some imidazo[l,5-tf][l,3,5]triazines with particular substitution patterns such that these compounds could be considered as nitrogen-positional isomers of some nucleobases. One of the typical synthetic steps is treatment of the diaminotriazine derivative 248 with phosphorus oxychloride to give the cyclized purinoid 249 in high yield (82%). Modification of this procedure also allowed preparation of the various oxo- and amino-related derivatives 250-252. 

As mentioned above, much less new information on imidazo[5,l-c][l,2,4]triazines appeared during the past years. Only one Russian team reported synthetic pathways to this ring system, and the results are summarized in Scheme 53. 

C-Acyclic nucleoside analogs of inosine and guanosine 8-[(/ 5)-2,3-dihydroxypropyl]imidazo[l,5-fl]-l,3,5-triazin-4(3//)-ones were synthesized. The route involved the cyclization and rearrangement of 5-acylamino-5-allyl-6-amino-4,5-dihydropyrimidin-4-ones (1122) to 8-allylimidazo[l,5-a]-l,3,5-triazin-4(3//)-ones (1123). Osmium tetroxide hydroxylation gave 1124. None of these analogs showed appreciable antiviral or antitumor cell activity (84NAR263 87MI6). 

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>. 

Azo compounds 61 under acidic conditions were reported to undergo a cyclization with elimination of 2-naphthol to give imidazo[4,5-rf][l,2,3]triazin-4-ones as unexpected major products with relatively little of the expected imidazole-A -1 cyclization products 62 isolated (Scheme 42) <2000CHE465>. 

Analogous to the synthesis of imidazo[4,5-,y [l,2,3]triazin-4-ones (Scheme 41), diazotization is the method of choice for making this ring system, and involves treatment of the 5-aminopyrazole-4-carboxamides with nitrous acid (Scheme 43) <1995JHC1417, 1996CHEC-II(7)489>. 

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>. 

The 5-0X0 substituent of the 3-alkylfervenulins 24 reacts with aqueous potassium permanganate to give the imidazo[4,5 ]-l,2,4-triazin-6-ones 66 via the ring-opening-ting-closure process suggested in Scheme 10 <1996JHC949>. 

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]

Reactions of 3-hydrazino-l,2,4-triazin-5-one derivatives with carbonyl compounds to give triazolotriazine derivatives have been reported <03KGS1376>. Intramolecular inverse electron demand cycloadditions of 2-substituted imidazoles with various 1,2,4-triazines produced both imidazo[4,5-c]pyridines (3-deazapurines) and pyrido[3,2-[Pg.387]

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