4-Diazoimidazole-5-carboxamide

Diazoimidazoles coupled with )8-dicarbonyl compounds to give the azo compounds that, upon heating, cyclized to imidazo-triazine (76JMC517). 4-Diazoimidazole-5-carboxamide (9a) (Scheme 63) reacted with /3-dicarbonyl compounds, but the cyclization to 2-azahypoxanthine... 

Diazoimidazole-5-carboxamide (9a) coupled in methanol with mer-capto derivatives to give the thioazo compounds 226 [73JAP24392 ... 

JAP(K)48664. 4-Diazo-5-thiocarbamoylimidazole at pH 5 intramolecu-larly cyclized with the more nucleophilic sulfur to give the imidazo-thia-diazine 228 instead of the imidazotriazine-4-thione 229, which was expected by analogy with the 4-diazoimidazole-5-carboxamide (73KGS1292) (Scheme 65). 

Diazoazoles have found wide application. Among the biological applications is the remarkable antineoplastic activity of several diazoazoles and in particular of 4-diazoimidazole-5-carboxamide. Chemical applications are extensive because of the high reactivity and versatility of the diazo/diazo-nium function. 

Further variations for the synthesis of this ring system has been published by M. F. G. Stevens et al. (Scheme 12). Thus, the methyl-substituted cyclic carbamate 37 when treated with sodium nitrite in aqueous tartaric acid yielded temozolomide 9a in average yield (45%) <1997JOC7288>. Two other approaches also proved to be applicable to the synthesis of a great number of derivatives the diazoimidazole carboxamide 32 was reacted with various isocyanates to... 

To this end, the diazoimidazole carboxamide compound 32 was transformed first by methylamine to the methyl-triazene derivative 39, which was reacted with 11 (". -phosgene to give the desired product 40 <2002JME5448>. In another approach, 32 was directly cyclized to the bicyclic product by using 1 C-labeled methyl isocyanate. This route allowed the synthesis of both the C-2-labeled 40 and the (7-methyl-labeled samples 41 <1997JLR371, 2002JME5448> (Scheme 13). 

The antitumour drug temozolomide 24 (R = Me) has been attracting attention and two new routes have been develqjed. One starts from 5-aminoimidazole-4-caiboxamide, whilst the other starts from 5-diazoimidazole-4-carboxamide which reacts with trimethylsilyl isocyanate to give 8-carbamoylimidazo[5,l-[Pg.272]

Dilute solutions in aqueous buffers exposed to diffused or direct sunlight gave dimethylamine and 5-diazoimidazole-4-carboxamide (215). At pH 1.0 or pH 7.4 and above, this cyclized to 2-azahypoxanthine (216). In the intermediate pH range, a different product was obtained (217) which happens to be the aglycone of the antibiotic bredinin. Compound (217) was not formed by irradiation of (216). It was suggested that the betaine arose from a carbene (218) which had been quenched by water. However, (217) is colourless. Formulated injection solutions which had been found to lose activity contained 10 mg/ml... 

Dacarbazine Dacarbazine, 5-(3,3-dimethyl-l-(riazeno)imidazol-4-carboxamide (30.6.5), is made by diazotation of 5-aminoimidazol-4-carboxamide with nitrous acid, which results in the formation of 5-diazoimidazol-4-carboxamide (30.6.4). Reacting this with dimethy-lamine gives the desired dacarbazine (30.6.5) [146]. 

Diazoimidazoles do not appear to have received very extensive study. The only fully authenticated diazoimidazole appears to be 5-diazoimidazole-4-carboxamide (57).32 Few reactions have been reported for this compound beyond its cyclization to 2-azahypo-xanthine (58). 

Diazoimidazole-4-carboxamide is an explosive compound which cyclizes to 2-aza-hypoxanthine (222a Scheme 121) <67AHC(8)l>. 

DIC undergoes stepwise demethylatlon to 5-aminoimidazole-4-carboxamide (AIC)The monomethylated intermediate (10)75 or dlazomethane76 nay be the active metabolites of DIC. The imidazole-4-carboxamide li (BIC) is transformed into an ionic product 12 in vivo which may explain the differences in antileukemic action and resistance development of DIC and BIC. 5 Cytotoxicity sttidy and preliminary clinical trlals 6 of BIC are reported. The action of 5-diazoimidazole-4-carboxamide (8) was studied in rabbit platelets the sulfhydryl group and pyrophosphate structures may be involved in the mechanism of release of 5-hydroxytrypfamine by 8. ... 

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