Imidazo pyrazine preparation

Diaminopyrazines undergo the expected condensation reactions with a,j8-dicarbonyl compounds. For example, condensation of 2,3-diamino-5,6-dimethylpyrazine with a,/9-diketones gives pyrazino-[2,3-h]pyrazines (124).38 2,3-Diaminopyrazines are also starting materials for the preparation of imidazo[4,5-6]pyrazines (123).117... 

Very few imidazo[4,5-b] pyrazines have been reported in the literature1-3 and no good general method has been available for preparing compounds in this most interesting heterocyclic class. We have found that the Curtius reaction of a 3-aminopyrazine-2-carboxylic acid azide (Scheme I) proceeds with intramolecular cyclization to provide, in good yield, a wide variety of the subject compounds. We will report here only the 6-substituted 5-chloro-l, 3-dihydro-2tf-... 

Some very clever syntheses of pyrazines were reported. Tandem Mn02-mediated oxidation followed by in situ trapping with aromatic or aliphatic 1,2-diamines was shown to give rise to quinoxalines, dihydropyrazines, pyrazines, and piperazines without the need to isolate highly reactive 1,2-dicarbonyl intermediates <03CC2286>. A new intramolecular cyclization route to highly substituted chiral 6,7-dihydro-5//-imidazo[l,5-a]pyrazin-8-ones like 157 from Meldrum s acid was developed <030L3907>, and 5-chloropyrido[3,4-6]pyrazines were prepared from 1,2-dicarbonyl compounds and 2-chloro-3,4-diaminopyridine <03H(60)925>. A synthesis of... 

The bromine of l-bromo-3-methylimidazo[l,5-a]pyrazine could not be displaced by a variety of nucleophiles. This contrasts with the reactivity of the 8-chloro substituent of (219 R = H or Me), prepared by the usual chlorination of the imidazo[l,5-a]pyrazin-8(7i/)-ones (218), which was readily displaced by thiourea to give the thiones (220). 

Treatment of imidazo[4,5-f>]pyrazine (225 R = H) with hydrogen peroxide in glacial acetic acid gave the 4-oxide (226 R = H) as the major product (50%) and the 4,7-dioxide (227 R = H) as the minor product. A 4-oxide was also obtained from the 1-methyl- and the l-(2,3,5-tri-0-acetyl-j8-D-ribofuranosyl)-imidazo[4,5-f)]pyrazine, in the latter case by means of MCPBA (73JMC643). Other 4-oxides and 4,7-dioxides have been prepared 75KGS690). 

Pyrazin-2-yl)imidazo[l,2-a]pyrazine (475) was obtained as a by-product (10%) in the ammonium chloride-catalyzed preparation of pyrazine carbaldehyde dimethyl acetal from the aldehyde (474) and trimethyl orthoformate (71TL1441). 

The chloromercuri procedure has also been utilized to prepare the ribonucleosides of 6-methylthiopurine, 6-methylpurine, a number of adenine derivatives, " 8-azapurines, and imidazo[4,5-d]pyrazines. ... 

The most useful synthesis of aromatic derivatives of this ring system involves condensation of aminomethylpyrazines 67 with anhydrides or carboxylic acids. Thus the amine 67 (R = H) was made to react with formic acid or acetic anhydride to give amides which were cyclized to the 3-substituted compounds 68. Clearly this synthesis could be extended to give a wide variety of substituted imidazo[l,5-a]pyrazines. Recently several more 3-substituted imidazo[l,5-a]pyrazines have been prepared from the amine 67 (R =... 

The known preparative methods for the synthesis of imidazo[l,5-a]pyrazines prior to 1983 have been extensively reviewed <84CHEC-I(5)607>. This section will review new methods of syntheses published since 1983. The most common syntheses of this ring system involve closure of the imidazole ring, usually by the conversion of 2-aminomethyl pyrazines, by means of acids or anhydrides, into amides, which are then cyclized to the target heterocycle. The newer methods all involve ring closure of the pyrazine ring. 

In recent decades, colorimetric and fluorometric sensors have been used in various scientific fields. In biology, for instance, such sensors are useful reagents for living cell imaging. It is important to design novel sensors because they have the potential to overcome many technical limitations in experiments. Imidazo[l,2-a]pyrazin- 3(7H)-one (imidazopyrazinone) often is used as a bioluminescent substrate, and it is an attractive core structure for useful sensors. In this regard, a new series of imidazopyrazinones [7-benzylimidazo[l,2 a]pyrazin-3(7H)-one derivatives] have been prepared and their fluorescent properties in the presence of various metal ions (Mn+) have been studied (Hirano, et al., 2010). 

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