Ethyl 4-aminoimidazole-5-carboxylate

For quantitative work, it is necessary to estimate the concentration of 5-amino-l-(P-D-ribofuranosyl)imidazole in aqueous solution. It seems that the only available method is the Bratton-Marshall assay, which was originally developed for the estimation of arylamines in biological fluids. The principle of the method is the spectrometric estimation of a salmon-pink colored dyestuff obtained by diazotation in situ, followed by coupling with /V-( 1 -naphthyl)ethyl-enediamine.65 The only remaining problem then is to know the molar extinction of this dye because pure samples of AIRs are not available. A value of 16800 at 520 nM was obtained for the dyes prepared from a model compound, 5-amino-l-cyclohexylimidazole-4-carboxylic acid (54), which is crystalline. A comparable molar extinction can be expected for the dye prepared from imidazole 55, if the carboxyl group does not exert too much influence on the chromophore. Actually, its influence is perceptible even with the naked eye, the dyestuff prepared from 53 having a somewhat different, wine-red color, with max>520 nM. The molar extinction for 55 is 17400 at 500 nM. When the decarboxylation of 54 was conducted under mild acidic conditions (pH 4.8, 50°C, 1 hour), estimation of 5-aminoimidazole 55 by the Bratton-Marshall method led to the conclusion that the reaction was almost quantitative.66 Similar conditions for the final decarboxylation were adopted in the preparation of samples of AIRs labeled with stable isotopes.58... 

The relative inaccessibility of C-AIR (107) promoted Shaw and co-workers [66JCS(C)2270] to use the 5-aminoimidazole-4-carboxylate (111 R = H) as a model compound since this was readily obtained as a crystalline sodium salt, in two steps from ethyl Af-(cyano-ethoxycarbonylmethyl)for-mimidate (110) and cyclohexylamine (Scheme 12) [62JCS(C)2937]. 5-Amino-l-cyclohexylimidazole (112 R = H) was obtained as the picrate salt (22%) from the sodium salt of the acid (111 R = H) by treatment of... 

The reaction of 2-aminoimidazole and EMME in boiling acetic acid for 3-6 hr yielded ethyl imidazo[l,2-a]pyrimidine-6-carboxylate (1113, R = R = H) (59JOC779). 

Similar to the above reactions is the isocyanide cycloaddition which leads to the regio-specific synthesis of ethyl 5-aminoimidazole-4-carboxylates (104,105 Scheme 59). 

Useful precursors for the preparation of substituted hypoxanthine derivatives are alkyl 4(5)-aminoimidazole-5(4)-carboxylates. Thus, reaction of ethyl 4-amino-l-arylimida7ole-5-carb-oxylates with thioamides in the presence of a catalytic amount of formic acid gives 2-substituted 7-arylhypoxanthines, e.g. formation of l. °... 

A series of new substituted purin-6-ones 2 have been prepared by heating ethyl 4-acyl-aminoimidazole-5-carboxylates with primary amine hydrochlorides and phosphorus pentoxide in N,N-dimethylcyclohexylamine. ... 

Aminoimidazole-2-carboxylates can be prepared by initial formation of the a-amidinonitrile (7) from ethyl formimidate and aminoaceionitrile. The amidinonitrile can then be cyclized by heating. The overall process, however, also occurs merely by heating the imidate (or thioimidate) and cr-aminonitrile... 

Analogous to the TOSMIC reactions is the cyclocondensation of an isothiourea with the enolate of ethyl isocyanoacetate (12) to give an alkyl 5-aminoimidazole-4-carboxylate (13). This regioselective synthesis provides... 

Both 4,5-difluoro- and 2,4-difluoroimidazoles have been prepared. The former was synthesized from ethyl 4-fluoroimidazole-5-carboxylate through a Curtius rearrangement that provided the Boc-protected 4-fluoro-5-aminoimidazole. In situ depro-... 

A number of isosteres of purines in the series of imidazo[5,l-/]-l,2,4-triazines have been obtained through the [5-fl] synthetic approach, starting from ethyl 1-aminoimidazole 5-carboxylate by the action of various reagents which can donate a C-N fragment (Scheme 155) <2005JOC7331>. 

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