Pyrido pyrazine preparation

Different azanthraquinones 390-392 were prepared from 3-amino-4-imino-4//-pyrido[l,2-a]pyrazines 373 with 1,4-quinones in one pot reactions via [4-1-2] cycloaddition and the subsequent ring transformation (Scheme 9) (97T5455). 

Quinoxalines have been prepared starting from common 1,2-diketones and 1,2-aryldiamines in MeOH/AcOH at 160 °C for 5 min under microwave irradiation (Scheme 81). Several differently substituted quinoxalines 223 and pyrido[2,3-b]pyrazines were prepared with this method, which Umitation may be the symmetry of the diketone 221 or the diamine 222 employed, in order to avoid the formation of a mixture of regioisomers [142],... 

Reaction of 3-amino-4-imino-4//-pyrido[l,2- ]pyrazine 306 (R = 4-MeC6H4) with ketenes 328, prepared in situ from the appropriate acetyl chloride with NEt3, yielded tricyclic derivatives 329 (Scheme 29) <1999JPR332>. Pyridine-3,4-dicarboxylates 330 were obtained from 4//-pyrido[l,2- pyrazines 307 with DMAD in refluxing toluene. 

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>. 

Derivatives of pyrido[2,3-f>]pyrazine were prepared from pyridyl-substituted AAs. Reductive cyclization afforded 115 (79CZ387), whereas cyclization with potassium carbonate gave the dione 116 (87TL6363). 

A unique acyclic C-nucleoside containing the pyrido[2,3-. ]pyrazine nucleus 675 was prepared by the action of AcOH, whereby rearrangement of 3 -keto-2 -deoxypyrazine C-nucleoside derivatives 673 occurs via the intramolecular aminal intermediate 674, followed by furanose ring opening and subsequent aromatization (Equation 56)... 

The treatment of 4-acetylpiperazinone 323 with LiHMDS, followed by addition of (C02Et)2 gave three condensation products 324-326. Upon addition of excess LiHMDS 8,9-dihydroxy-3,4-dihydro-lH,6H-pyrido [l,2-fl]pyrazine-l,6-dione 327 was obtained in low yield (07BML5595). The major isomer 324 could be izomerized into 325 on the action of TFA in aqueous MeCN, which readily cyclized to pyrido[l, 2-aJpyrazine-l, 6-dione 327. 14C-labeled 327 was also prepared using 14C-labeled diethyl oxalate. 

Lindsley and co-workers developed a general procedure towards the collection of diverse heterocyclic scaffolds from common 1,2-diketone intermediates 96. Substituted quinoxalines 97, fused pyrazolo [ 4,5-g ] quinoxalines 98 and imidazolo[3,4-g]quinoxalines 99 as well as pyrido[2,3-fo]pyrazines 100 and Ihicno[3,4-fo Ipyrazincs 101 have been prepared in excellent yields [132] (Scheme 54), employing optimized reaction conditions (microwave heating of equimolar mixtures of 1,2-diketone 96 and diamine components at 160 °C for 5 min in 9 1 MeOH - AcOH). The use of microwave irradiation resulted in reduced reaction times (5 min vs. 2-12 hours), improved yields as well as the suppressed formation of polymeric species a characteristic of traditional... 

Pyrazine diquatemary salts of types 16lB1 and 17152 are known and also 6,7-dihydro derivatives of 16.152a The diquaternary salt (17) was originally formulated as the monohydrate of 18, but attempts to dehydrate 17 to 18 have not been successful.152 Dipyrido[l,2-a 2, l -c]pyrazinium dibromide (16) has herbicidal properties it is reduced in aqueous solution to a stable radical cation.183 The related pyrido[l,2-a]pyrazinium salts of type 19 have also been prepared.153,1B4a... 

Hexahydro-l//-pyrido[l,2-a]pyrazin-l-ones were prepared by oxidation of 2-substituted perhydropyrido[l,2-a]pyrazines and perhydro-pyrido[l,2-a]pyrazin-l-one with Hg(OAc)2 in 5% aqueous AcOH (73CPB1248). Oxidation of l,3,4,6,ll,lla-hexahydro-2//-pyrazino[l,2-bjisoquinoline with Hg(OAc)2 in 5% aqueous AcOH gave the 6-oxo derivative [73CPB2039 77IJC(B)70]. l,3,4,6,ll,lla-Hexahydro-2//-... 

Heating either trimethyl 2-methyl-6-ethylidene-2,6-dihydro-l//-pyrido[l,2a]-pyrazine-7,8,9-tricarboxylate or tetramethyl 1,2-dimethyl-2,9a-dihydro-l//-pyrido-[l,2-a]pyrazine-6,7,8,9-tetracarboxylate in dilute HC1 gave dimethyl 2-methyl-7-propionyl-l,6-dioxo-2,6-dihydro-l//-pyrido[l,2-a]pyrazine-8,9-dicarboxylates (62JCS1510). 1,12-Dihydroxyper-hydrodibenzo[ac]pyrazine was prepared from l-(2-tetrahydrofuryl)-9-hydroxyperhydropyrido[l,2-a]pyrazine in AC2O saturated with HBr at 95-100°C (61BSF2135). 

Benzylperhydropyrido[l,2-a]pyrazin-6-one was prepared through the cyclization of 287, obtained from 285 via 286 (93JOC690). From the reaction mixture of 2,3-di(2-tetrahydrofuryl)piperazine, treated with HBr gas in AcOH at 90-95°C, then with KOH, l-(2-tetrahydrofuryl)-9-hydroxy-perhydropyrido[l,2-a]pyrazine could be isolated (61BSF2135). Cyclization of 2-(l,2,3,4-tetrahydroxylbutyl)quinoxalines in an acidic media gave 8H-pyrido[l,2-a]quinoxalin-8-ones together with a small amount of their 9-... 

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