2-Chloro-5-methoxypyrazine

Chloro-3-methoxy-2-pyrazinamine 2-Chloro-3-methoxypyrazine 2-Chloro-5-methoxypyrazine 2-Chloro-6-methoxypyrazine 6-Chloro-3-methoxy-2-pyrazinecarbonitrile 6-Chloro-3-methoxy-2-pyrazinecarboxamide 2-Chloro-6-methylamino-3,5-diphenylpyrazine 2-Chloro-3-methylaminopyrazine 6-Chloro-3-methylamino-2-pyrazinecarboxamide 5-Chloro-6-methylamino-2,3-... 

A cyano group produces practical reactivity (methanolic CH30, 66°, < 3hr) by its presence in 2-chloro-3-cyano-6-methylpyridine, opposing the deactivating effect of a methyl group, and on other 2-chloropyridines (see references 3-6 in ref. 140). The cyano group activates 3-cyano-6,6-diphenyl-2-methoxypyrazine (168) (pre-... 

Examples of the 3-lithiation of both 2- and 2,6-disubstituted chloro- and methoxypyrazines, as well as 2-thiomethylpyrazine are known (88S881 90JOC3410 91JHC765, 91JOM(412)301] (Scheme 117). As with pyridazine, LiTMP has so far been the only base employed, and this same base system has also recently been used for the directed metalation of pyrazine... 

Chloro- (127, R = Cl) or 2-lluoropyrazine 1-oxide (127, X = F) gave 2-methoxypyrazine 1-oxide (128) [MeONa, MeOH, reflux 45 min 85% (from chloro substrate) or MeONa, MeOH, 20°C, 10 min 91% (from fluoro substrate)].276... 

Chloro-3,6-difluoro-5-hydrazinopyrazine 2-Chloro-3,6-difluoro-5-methoxypyrazine 2-Chloro-3,6-diisobutyl-5-methoxypyrazine 2-Chloro-3,6-diisobutylpyrazine 2-Chloro-3,6-diisobutylpyrazine 1, 4-dioxide... 

Chloro-5-isobutylpyrazine 6-Chloro-5-isobutyl-2-pyrazinecarbothioamide 6-Chloro-5-isobutyl-2-pyrazinecarboxamide 2-Chloro-3-isobutylpyrazine 4-oxide 2-Chloro-5-isopentyl-3,6-dimethylpyrazine 2-Chloro-3-isopropenyl-6-isopropyl-5-methoxypyrazine 5-Chloro-6-isopropenyl-3-isopropyl-l-methyl-2(177)-pyrazinone... 

Q-(p-Toluenesulfonyloxyiinino)malononitrile (104), when treated with malono-nitrile in basic conditions, has been shown to give salts of l,l,3,3-tetracyano-2-azapropenide (105), which with concentrated sulfuric acid in methanol gave 2-amino-3,5-dicyano-6-methoxypyrazine (106) (484) and with hydrochloric acid in acetone gave 2-amino-6-chloro-3,5-dicyanopyrazine (485, 486). Catalytic cyclization of 2-(2 -aminobutylamino)butanol with Raney nickel has been found to give a mixture of 2,5-diethylpiperazine (25% yield) and 2,5-diethylpyrazine (8%) (487). 

Chloro-3-morpholinopyrazine treated with allyl alcohol followed by bromination in the presence of water has been shown to give 5-bromo-2-(3 -bromo-2-hydroxypropoxy)-3-morpholinopyrazine (813), and bromination of 2-amino[or 2-(p-toluenesulfonamido)]-3-methoxypyrazine with a mixture of potassium bromide and bromate in 6N sulfuric acid gave 2-amino-[or 2-(p-toluenesulfonamido)]-5-bromo-3-methoxypyrazine (814). The bromination (814) of 2-methoxy-3-sulfanilamidopyrazine in methanol was anomalous (815,816) [see Section 5D(2)]. 

Deuterolysis of 3-chloro-2-chloromethyl-5-methoxypyrazine over 5% palladium on alumina in the presence of sodium isopropoxide in 2-propanol afforded 3-deutero-2-monodeuteromethyl-5-methoxypyrazine (687) and methylation of the bromomagnesium derivative from 2-bromomethyl-3,5,6-trimethylpyrazine with methyl sulfate or methyl iodide gave 2-ethyl-3,5,6-trimethylpyrazine (330). 

Other hydrolyses with sodium hydroxide have been described as follows. 2-Benzyloxy-6-chloropyrazine in ethanol with 3.5N sodium hydroxide at reflux for 4.5 hours gave 2-chloro-6-hydroxypyrazine (832), 2-chloro-6-metho)Qrpyrazine with aqueous ethanolic sodium hydroxide gave 2-chloro-6-hydroxypyrazine (43%) possibly containing a small amount of 2-hydroxy-6-methoxypyrazine) (883), and 2,6-dimethoxypyrazine with aqueous ethanolic sodium hydroxide at reflux for 24 hours formed 2-hydroxy-6-methoxypyrazine (832). 

Methoxypyrazines (31) have been prepared by diazomethane methylation of 2-hydroxy-3-isobutylpyrazine (60, 311, 367), 2-hydroxy-3-isopropylpyrazine (59, 367), 2-hydroxy-3-propyl(ethyl or hexyl)pyrazine (367), 3-hydroxy-2-isobutyl-5(and 6)methylpyrazine and 2-hydroxy-3-isobutyl-5,6-dimethylpyrazine (368), 2,3-dihydroxypyrazine (832), 2-hydroxy-5-methoxy- and 2,5-dihydroxy-3,6-diphenyl-pyrazine (832), 2-hydroxy-6-methoxy(and benzyloxy)pyrazine (832), 2,6-dihydroxy-3,5-diphenylpyrazine (873), 2,3,5-trifluoro-6-hydroxypyrazine (851), 2-chloro-6-hydroxy-3,5-diphenylpyrazine (873), 2-chloro-6-hydroxy-5-methyl-3-phenylpyrazine (873), 2-chloro-6-hydroxy-3-methyl-5-phenylpyrazine (873), 5,6-dichloro-1 -cyclohexyl-34iydroxy-2-oxo-l, 2-dihydropyrazine (853), 2-chloro-5-hydroxy-3-methoxy-6-methoxycarbonylpyrazine (881), 2-(4 -amino-3, 5 -dibromo-phenylsulfonamido)-3Tiydroxy-6-methoxypyrazine (881), 2-amino-3-hydroxy-... 

Deoxygenation with formation of Chloro-, Acetoxy-, and Methoxypyrazines... 

When heated with aqueous potassium hydroxide, 2,5-dicyano-3,6-dimethyl(and diphenyOpyrazine gave 2-carboxy-5-hydroxy-3,6-dimethyl(and diphenyl)pyrazine (286-288) and the diethyl analogue was prepared similarly (287). 2-ChIoro-6-cyanopyrazine refluxed with three equivalents of sodium methoxide for 2 hours gave 2-carboxy-6-methoxypyrazine, also obtained from 2-chloro-6-cyanopyrazine with one equivalent of sodium methoxide through 2-(C-imino-C-methoxymethyl)-6-methoxypyrazine (2), which, refluxed with 15% sodium hydroxide, gave 2-carboxy-6-methoxypyrazine (986). 

Dimethoxycarbonylpyrazine heated with hydrazine hydrate in ethanol gave some 5,8-dihydroxypyrazino[2,3-with hydrazines (and amines) has been described in Section 2C(2)(a) (961,1330, 1331). An analogous active ester was prepared from 2-amino-3-carboxy-5-chloro-6-methoxypyrazine and with hydrazine in tetrahydrofuran gave 2-amino-5-chloro-... 

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