2- 1 -Phenyl-1 ’- methyl pyrazine

Beim kurzen Erhitzcn in waBriger Natronlauge dehydratisiert 3-Amino-2-(amino-benzoyloxi-mino-methyl)-pyrazin in guter Ausbeute zu 3-(3-Amino-2-pyrazinyl)-2-phenyl-l,2,4-oxadi-azol (77% Schmp, 220-2230)211 ... 

Another key intermediate for pteridine synthesis was also seen in 2-amino-3-ethoxycarbonyl-5-phenylpyrazine 1-oxide which reacts with various amines to form the corresponding amides followed by cyclization with triethyl orthoformate giving 3-alkyl-6-phenyl-4(3/7)pteridinone 8-oxides <87JHC1109>. The synthesis of 2,4-diamino-6-methylpteridine 5-oxide (371) was achieved from 5-methyl-pyrazine-2-carboxamide (366) via the 4-oxide (367), a Hofmann degradation (368), bro-mination (369), and cyanation (370) followed by cyclization with guanidine to give (371) (Scheme 60) <93JHC841>. 

Oxidation of nuclear and extranuclear hydroxypyrazines (and derivatives) to their Af-oxides has been achieved with hydrogen peroxide in acetic acid, and with m-chloroperoxybenzoic acid in 1,2-dichIoroethane. 3-Hydroxy-2,5-diisobutyl-pyrazine was oxidized with 30% hydrogen peroxide in acetic acid at 70 to 3-hydroxy-2,5-diisobutylpyrazine 1-oxide (101), 3-hydroxy-2-(Af-methyl-A -phenyl-carbamoyl)pyrazine 1-oxide (90) was also prepared from the conesponding pyrazine [its A -4-methyl derivative was prepared similarly and also by methylation of (90) (1055)], and 3-hydroxy-2-(A -methyl-AAp-tolylcarbamoyl)pyrazine 1-oxide (1055) was synthesized analogously. 

Typical preparations have been described for 2-(r-hydroxyiminomethyl)pyrazine (138) 2-(4 -dimethylamino-T-hydroxyiminobutyl)pyrazine (1186) 2-(2 -hydroxy-iminopentyl)-6-methylpyrazine (645) 2-(2 -hydroxyimino-3, 3 -dimethylbutyl)-6-methylpyrazine (645) 2-[r-hydroxyimino-2-(pyridin-2"-yl) (hyl]pyrazine (642) 2-[2 -hydroxyimino-2 -(pyridin-2"-yl, pyrazin-2"-yl, or pyrimidin-4 -yl)ethyl]pyrazine (642) 2-[l, 2 -bishydroxyimino-2 -(pyridin-2"-yl)ethyl]pyrazine (642) 2-12 -(2",4"-dinitrophenylhydrazono)-3 -methylbutyl]-6-methylpyrazine (645) 2-[ 1-(substituted hydrazono)ethyl]pyrazine (1196) 2-[l -phenyl-1 -(substituted hydrazono)methyl]-pyrazine (1196) 2-(r-thiosemicarbazonoethyl)pyrazine (138) 2-(2 -chloro-l -thiosemicarbazonoethyOpyrazine (138) and 2,5-dimethyl-3,6-bis(r-semicarbazono-ethyl)pyrazine (1196). 

Amino-5-methyl-6-phenyl-2-pyrazine-carboxylic acid... 

Pyrazine, 2-amino-5-methyl-synthesis, 3, 180, 181 Pyrazine, 2-amino-5-phenyl-synthesis, 3, 180, 181... 

Nakano, M., Sugioka, K., Ushijima, Y., and Goto, T. (1986). Chemiluminescence probe with Cypridina luciferin analogue, 2-methyl-6-phenyl-3,7-dihydroimidazo[l,2-a]pyrazine-3-one, for estimating the ability of human granulocytes to generate superoxide anion. Anal. Biochem. 159 363-369. 

One interesting example of this type of synthesis has been reported. 6-Phenyl-5//-5,7(6F/)-pyrrolo[3,4-/>]pyrazine (515) underwent electrolytic reduction in the presence of chlorotrimethylsilane to give the (unisolated ) substrate (516) that reacted with methyl acrylate (minimal detail) to afford a mixture of methyl 8-anilino-5-oxo-l,5-dihydro-6-quinoxalinecarboxylate (517) and methyl 5-ani-lino-8-oxo-4,8-dihydro-6-quinoxalinecarboxylate (517a) (17% and 21%, respectively, after separation). 

Substituted pyrimidine N-oxides such as 891 are converted analogously into their corresponding 4-substituted 2-cyano pyrimidines 892 and 4-substituted 6-cya-no pyrimidines 893 [18]. Likewise 2,4-substituted pyrimidine N-oxides 894 afford the 2,4-substituted 6-cyano pyrimidines 895 whereas the 2,6-dimethylpyrimidine-N-oxide 896 gives the 2,6-dimethyl-4-cyanopyrimidine 897 [18, 19] (Scheme 7.6). The 4,5-disubstituted pyridine N-oxides 898 are converted into 2-cyano-4,5-disubsti-tuted pyrimidines 899 and 4,5-disubstituted-6-cyano pyrimidines 900 [19] (Scheme 7.6). Whereas with most of the 4,5-substituents in 898 the 6-cyano pyrimidines 900 are formed nearly exclusively, combination of a 4-methoxy substituent with a 5-methoxy, 5-phenyl, 5-methyl, or 5-halo substituent gives rise to the exclusive formation of the 2-cyanopyrimidines 899 [19] (Scheme 7.6). The chemistry of pyrimidine N-oxides has been reviewed [20]. In the pyrazine series, 3-aminopyrazine N-ox-ide 901 affords, with TCS 14, NaCN, and triethylamine in DMF, 3-amino-2-cyano-pyrazine 902 in 80% yield and 5% amidine 903 [21, 22] which is apparently formed by reaction of the amino group in 902 with DMF in the presence of TCS 14 [23] (Scheme 7.7) (cf. also Section 4.2.2). Other 3-substituted pyrazine N-oxides react with 18 under a variety of conditions, e.g. in the presence of ZnBr2 [22]. 

Stereostructures of a co-crystal of (li )-l- 4-[(9aA)-perhydropyrido[l,2- ]pyrazin-2-yl]phenyl -2-phenyl-7-hydroxy-l, 2,3,4-tetrahydroisoquinoline with ERa-LBD301-553/C — S triple mutant <2005JME364> and iV-[2-(4-hydroxyphenyl)ethyl]-a-propyl-3-[(4-hydroxyphenyl)methyl]-l,4-dioxo-l,2,3,4,ll,l la-hexahydro-67/-pyrazino[l,2- ]isoquinoline-3-acetamide with fructose-1,6-biphosphatase <2003JBC51176> were determined by X-ray crystallography. The structure of a complex formed from 3-[( -methylphenyl)amino]-4-[(4-methylphenyl)imino]-4//-pyrido[l,2-tf]pyrazine with sodium bis(trimethylsilyl)amide and (norbornadiene)Mo(CO)4 in THF was characterized by single crystal X-ray diffraction <1995JPR38>. 

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