2- pyrazine cyclocondensation

Swain and Brown 1952). It was therefore proposed that the pyridine-2,3-diamine 482 may also behave as a catalyst for the ring opening of starting pyrrolidinone 479. This would allow the pyrazine cyclocondensation to take place and the combination of both factors may explain the observed mixture of regioisomers (Adlington et al. 2001). 

Cyclocondensation of 2-aminomethylpiperidine 422 and dimethyl oxalate yielded perhydropyrido[l,2-n]pyrazine-3,4-dione 423 (00T1005). 

Perhydropyrido[l,2- ]pyrazin-l-one was prepared in the reaction of methyl pipecolinate and ethylene imine in boiling EtOH <19951JSP5461047>. Cyclocondensation of ethyl 2-amino-2-(2-pyridyl)acetate with DMAD, followed by treatment of reaction mixture with NaOMe, gave the 2-(l-methoxycarbonyl)-4-oxo-47/-pyrido[l,2- ]pyrazin-3-yl)acetate <1996JHC639>. 

Cyclocondensation of 2-aminomethylpiperidine 395 and (C02Me)2 yielded perhydropyrido[l,2-tf]pyrazine-3,4-dione 396 (Equation 73) <2000T1005>. Reaction of a 2-(tosylamino)methylpyridine with (CH2Br)2 afforded a... 

Amino-3-(methoxycarbonyl)pyrazine 89 is a versatile reagent for the cyclocondensation reactions leading to heterocondensed pteridines 90-93 (Scheme 6) <2001JHC1173>. 

A different approach to quinoxalines and heterocycle-fused pyrazines has been described by the Lindsley group, based on the cyclocondensation of 1,2-diketones and aryl/heteroaryl 1,2-diamines (Scheme 6.260) [450]. Optimized reaction conditions involved heating an equimolar mixture of the diketone and diamine components for 5 min at 160 °C in a 9 1 methanol/acetic acid solvent mixture, which furnished the substituted quinoxalines in excellent yields. This approach could also be applied equally successfully to the synthesis of heteroaryl pyrazines, such as pyr-ido[2,3-b]pyrazines and thieno[3,4-b]pyrazines. The same group has employed 1,2-diketone building blocks for the preparation of other heterocyclic structures (see Schemes 6.198, 6.268, and 6.269). 

Cyclocondensation of 3-amino-2-methylaminopyridine 647 or 2-amino-3-methylaminopyridine 651 with 2-keto-glutaric acid gave 2-carboxyethyi-4-methylpyrido[2,3-i)]pyrazin-3(4/7)-one 652 and its 3-carboxyethyl-2(l/7)-one isomer 653, respectively (Equation 54) <1994FA259>. 

Cyclocondensation of bromoacetaldehyde oxime with 2-benzoylpyridine and 2-cyanopyridine gave l-phenylpyrido[l,2-a]pyrazin-5-ium bromide 2-... 

Cyclocondensation of pipecolinic acid and malic acid anhydride in pyridine afforded 3-hydroxy-2,3-dimethylperhydropyrido[l,2-a]pyrazine-l, 4-dione (74CB2804). Cyclocondensation of bis(2,4,6-trichlorophenyl) mal-onates with 2-methyl-, 2-benzyl- and 2-ethoxycarbonylmethylquinoxalines and -3-ones at 250°C afforded 8-hydroxy-10//-pyrido[l,2-a]quinoxalin-10-ones and their 5,6-dihydro-6,10-dione derivatives (77M103). Under Horner-Wittig reaction conditions, the reactions of 2-formylquinoxaline and dialkyl phosphonosuccinates (314) also involved cyclization to give alkyl 10-oxo-10//-pyrido[l,2-a]quinoxahne-8-carboxylate (80LA542). 

There is a paucity of functional group reactions associated with the pyrrolopyrazines. A few examples may be found within the references describing their syntheses. However, a reaction has been reported which describes the [4 + 2] cycloaddition of pyrrolopyrazines. Ring expansion of 2-phenyl-2//-pyrrolo[3,4-/ ]pyrazine (32) occurs through cyclocondensation of the trimethylsilyl ether (33) with, amongst other dienophiles, methyl acrylate, and a mixture of quinoxalines (34) is obtained in 38% yield (Scheme 2) <86JHC1641>. 

Ar-Benzyl-A,A-bis(tosylmethyl)amine gave 1,4-dibenzylpiperazine (Sml2, THF—(Me2N)3PO, 5 min Et2CO -65% minimal detail).1620 Note One postulated cyclocondensation with dissimilar C—N—C synthons to give a pyrazine has been reported without details.1129... 

Of all the possibilities for producing a pyrazine ring from three synthons, only one type of cyclocondensation has emerged from the present survey it involves the reaction of a C—C synthon with two identical N—C synthons, as indicated in the following examples ... 

Ethyl 2-pyrazinecarboxylate (103, R = Et) gave 2-acetoacetylpyrazine (106) (AcMe, EtOK, THF, reflux, 6 h crude), characterized by cyclocondensation with H2NNH2 to give 2-(5-methylpyrazol-3-yl)pyrazine (107) (EtOH—H20, reflux, 5 h 44% overall).1501... 

Note One postulated cyclocondensation with dissimilar C—N—C synthons to give a pyrazine has been reported without details. - ... 

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