Imidazo pyrazine reactions

Imidazo[4,5-fe]pyrazine, 2-methyl-synthesis, 5, 645 lmidazo[l,2-a]pyrazines reactions, 5, 624 synthesis, 5, 642-643 Imidazo[ 1,5-a]pyrazines chlorination, 5, 625 reactions, 5, 625-626 synthesis, 5, 644-645 Imidazo[4,5-fc]pyrazines reactivity, 5, 626-627 synthesis, 5, 645-646... 

Microwave and fluorous technologies have been combined in the solution phase parallel synthesis of 3-aminoimidazo[l,2-a]pyridines and -pyrazines [63]. The three-component condensation of a perfluorooctane-sulfonyl (Rfs = CgFiy) substituted benzaldehyde by microwave irradiation in a single-mode instrument at 150 °C for 10 min in CH2CI2 - MeOH in the presence of Sc(OTf)3 gave the imidazo-annulated heterocycles that could be purified by fluorous solid phase extraction (Scheme 9). Subsequent Pd-catalyzed cross-coupling reactions of the fluorous sulfonates with arylboronic acids or thiols gave biaryls or aryl sulfides, respectively, albeit it in relatively low yields. 

Reaction of pyrido[ 1,2- pyrazin-4-one 304 with methyl cyanoacetate, cyanamide, and JI-oxo nitriles in AcOH at 70 °C gave imidazo[ l,2- ] pyridine 331, imidazo[l,2- ]-pyrimidine 332, and tetracyclic heterocycles 333, respectively <1996JHC639>. 

An efficient one-pot synthesis of some novel azolo[l,5-a]pyrimidines, via enaminonitriles, has been described <00SC1985>. The utility of 3-aminocinnamonitrile in the synthesis of new pyrazolo[l,5-a]pyrimidines has been reported <00ZN(B)321>. The synthesis of novel arylaminopyrazolo[3,4-d]pyrimidin-4-ones has been described <99IJC(B)1075>. The synthesis and properties of a-Thiagra, a substituted 5-(2-thienyl)pyrazolo[4,3-d]pyrimidin-7-one bioisostere of Viagra, have been described <00H(53)2643>. Imidazo[4,5-b]pyrazines are obtained by the reaction of 4-amino- 5-imino-imidazole derivatives with acetophenone dimethylacetal . 

Imidazo[l,5-a]pyrazine, hexahydro-synthesis, 5, 644-645 Imidazo[l,5-a]pyrazine, 3-methyl-Mannich reaction, 5, 625 Imidazo[l,5-a]pyrazine, 3-(methylthio)-reactions... 

Imidazo[l,5-a]pyrazin-8(7H)-ones sjmthesis, 5, 625 Imidazo[4,5-6]pyrazin-2-ones reactions, 5, 626 synthesis, 5, 645, 646 lH-lmidazo[l,2-f>]pyrazole, 2,3-dihydro-synthesis, 6, 991 Imidazo[4,5-c]pjrrazole,... 

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... 

Reaction of pyrido[l,2-a]pyrazin-4-one 145 with methyl cyanoacetate, cyanamide, and /3-oxo nitriles in AcOH at 70°C gave imidazo[l,2-a]pyridine 147, imidazo[l,2-u]pyrimidine 148, and tetracyclic heterocycles 149, respectively (96JHC639). 

Syntheses of fused mesoionic heterocycles such as [l,2,3]triazolo[l,5-a]-quinoline, -quinazoline, -quinoxaline, and -benzotriazine derivatives have been described <02T3185>. Cyclizations of alkyl 2-benzoylamino-(4,5-dicyano-1 //-1,2,3-triazol-1 -yl)propenoates gave [1,2,3]triazolo[l, 5-a]pyrazines <02H(56)353>. Reaction of triethyl N-( 1 -ethy 1-2-methy 1-4-nitro-l//-imidazol-5-yl)phosphorimidate with aryl isocyanates provided a route to 2-aryI-2//,4//-imidazo[4,5-fif][l,2,3]triazoles <02JCS(P 1)1968>. 2-(A,A-Diphenylamino)-4-hydrazino-6-... 

The thermal Curtius reaction of a 3-aminopyrazine-2-carboxylic acid azide proceeds with intramolecular cyclization to provide a versatile synthetic route to a wide variety of 1,3-dihydro-2tf-imidazo[4,5-i]-pyrazin-2-ones. Many compounds in this series are potent hypotensive agents in animals they are also inhibitors of the enyzme cyclic AMP phosphodiesterase in vitro. 

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-... 

Various imidazo[4,5-fc]pyrazin-2-ones (228) have been subjected to a number of different reactions. Alkylation, acylation and the Mannich reaction all give 1,3-disubstituted derivatives (229). Halogenation of the 2-oxo compound (230) with bromine or chlorine in acetic acid or with sulfuryl chloride provided monohalo derivatives (231) (69FRP1578366, 71BRP1248146). The chlorine atom of (231) can be removed by catalytic hydrogenation. 

Distillation of l,2,3,4-tetrahydropyrido[3,2-ii]pyrimidine-2,4-dione (384) with zinc dust caused a reductive rearrangement to imidazo[4,5-h]pyridine (385) (56JCS1045). Reaction of 6-chloropyrido[2,3-h]pyrazines (386) with potassium amide in liquid ammonia resulted in attack at C-2 giving (387), with ring contraction to (388) involving loss of chlorine to give imidazo[4,5-h]pyridine or 2-substituted derivatives thereof (389) (79JHC305). 

One of the few examples of formation of the pyrazine ring as the last step in the synthesis of imidazo[4,5-fe]pyrazines (504) involves the reaction of biacetyl with the diamine (503) generated in situ from the 4-nitro-5-amino compound (502) (70TL1013>. Another synthesis involving the use of an imidazole is the condensation of ethylenediamine (505) with (506) to give the perhydro derivative (507). 

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