2-Bromo-3-methoxycarbonylpyrazine

Bromo-3-methoxycarbonylpyrazine with 2,3-dimethylaniline in refluxing toluene gave 2-(2, 3 -dimethylphenyl)amino-3-methoxycarbonylpyrazine (950) [hydrolysis of this product with sodium hydroxide in ethanol gave 2-carboxy-3-(2, 3 -dimethylphenyl)aminopyrazine, which was also obtained by treatment of l-(2, 3 -dimethylphenyl)lumazine with sodium hydroxide in refluxing ethanol (950)]. 3-Bromo-2-hydroxy-5-phenylpyrazine with ammonium hydroxide and copper at 150° gave 3-amino-2-hydroxy-5-phenylpyrazine (365a). Replacement of the iodo substituent from 2-amino-5-iodo-3,6-dimethylpyrazine has been effected with ammonium hydroxide (887). 

The diazotization of aminopyrazines has been described in earlier sections. Section V.IH records the preparation of 2-fluoropyrazine from 2-aminopyrazine in fluoroboric acid containing copper powder with sodium nitrite (882, 884) and Section V.ll the preparation of iodopyrazines from some aminopyrazines via isodiazotate salts (30) (887). These salts were assigned the isodiazotate structure, on the basis of their inability to couple with 0-naphthol in alkaline solution (887) and they were characterized by hydrolysis in cold 40% aqueous sulfuric acid to the hydroxypyrazine (887). Section V.I K describes the conversion of aminopyrazines to bromopyrazines (798, 800, 807, 890-892) for example, 2-amino-3-methoxy-carbonylpyrazine with hydrobromic acid, bromine, and sodium nitrite in water gave 2-bromo-3-methoxycarbonylpyrazine (798, 890). The diazotization of aminopyrazines to hydroxypyrazines has been described in Section VI. 1C, to alkoxy-pyrazines in Section V1.3C, and to oxopyrazines in Section V1.9A(5). 2-Amino-pyrazine with isopentyl nitrite in benzene gave 2-phenylpyrazine (45%) and some 2-isopentoxypyrazine and 2,2 -dipyrazinyl amino isomers (1211). 

Bromination of 2-amino-3-methoxycarbonylpyrazine in acetic acid gave 2-amino-5-bromo-3-methoxycarbonylpyrazine (787, 798) and the 2-methylamino analogue... 

Amino-3-hydroxypyrazine with phosphoryl bromide at 140-150° for 20 minutes gave 2-amino-3-bromopyrazine (807) and 2-hydroxy-6-methoxycarbonyl-pyrazine with phosphoryl bromide at 125° for 10 minutes gave 2-bromo-6-methoxycarbonylpyrazine (867). 

Aminopyrazine was oxidized by hydrogen peroxide in acetic acid at 20° to 3-aminopyrazine 1 -oxide and at 50° for 15 hours to 2-aininopyrazine 1,4-dioxide (51%) (also obtained by similar oxidation of 3-aminopyrazine 1-oxide) (1189). m-Chloroperoxybenzoic acid was also used for the oxidation of 2-aminopyrazine to its 1-oxide (1258). The following aminopyrazine TV-oxides have been prepared by oxidation (reagent and conditions) 2-amino-3-methoxycarbonylpyrazine 1-oxide (m-chloroperoxybenzoic acid in chloroform at reflux) (880, 1222) 2-amino-5-chloro-3-methoxycarbonyl(and methylcarbamoyl)pyrazine 1-oxide (m-chloroperoxybenzoic acid in chloroform at reflux) (1222) 2-amino-5-bromo-3-methoxycarbonylpyrazine 1-oxide (wperoxyacetic acid) (906) 2-amino-3-bromo-5,6-dimethylpyrazine 1-oxide (peroxyacetic acid) (907) and 2,3-bis(pyridin-2 -yl)pyrazine 1,4-dioxide (hydrogen peroxide in sulfuric acid at room temperature) (754). 

The brominations of 2-amino-3-carboxypyrazine (804), 2-amino-5-bromo-3-carboxypyrazine (805, 806), and 2-amino-5-bromo-3-methoxycarbonylpyrazine (807) to 2-amino-3,5-dibromopyrazine have been described in Section V.IB (2) nitrations of 2-amino-3-carboxy-5-chloro-6-ethylaminopyrazine to 2-amino-5-chloro-6-ethylamino-3-nitropyrazine (1181) and 2,6-diamino-3,5-dicarboxypyrazine... 

Dimethoxy-2-methoxycarbonylpyrazine boiled with phosphoryl chloride and phosphorus pentachloride gave the acid chloride, which, treated with aqueous hydrazine, gave 2-hydrazinocarbonyl-3,5-dimethoxypyrazine (881). 2-Methoxy-3-methoxycarbonyl-5-methylpyrazine with methylmagnesium iodide in ether gave 3-(l -hydroxy-r-methylethyl)-2-methoxy-5-methylpyrazine (39) (844). Thebromi-nation of 2-amino-5-bromo-3-methoxycarbonylpyrazine in 30% hydrobromic acid to 2-amino-3,5-dibromopyrazine has been described in Section V.IB (2) (807). 

Alkoxycarbonylpyrazines have been oxidized to alkoxycarbonylpyrazine Af-oxides as follows 2-ethoxycarbonylpyrazine with perhydrol gave 3-ethoxy-carbonylpyrazine 1-oxide (575) 2-amino-3-methoxycarbonylpyrazine refluxed with m-chloroperoxybenzoic acid in chloroform gave 2-amino-3-methoxycarbonyl-pyrazine 1-oxide (876,880,1222) the 5-bromo (808, 877,878, 1222) and 5-chloro (875, 876, 879, 1222) derivatives were prepared similarly and some 3-ethoxy-carbonylpyrazine 1-oxides have been prepared by oxidation (reagent not stated) of... 

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