Cyanopyrazines with amines

Chloro-6-cyanopyrazine with anhydrous methylamine (940), diethylamine, and other amines in refluxing benzene (941,942), thiomorpholine, and A -methyl-... 

Cyanopyrazine with concentrated aqueous ammonia was converted through 2-[A(-(C-imino-C-pyrazin-2-ylinethyl)amidino]pyrazine (43) to 2-carbamoylpyrazine (985), and 2-chloro-6-cyanopyrazine reacted similarly (985). 2-Ethoxy-6-(C-ethoxy-C-iminomethyl)pyrazine was found to be a by-product of the reaction of 2-chloro-6-cyanopyrazine with concentrated ethanolic ammonia and 2-ethoxy(or methoxy)-6-[C-ethoxy(or methoxy)-C-iminomethyl]pyrazine was obtained from 2-chloro-6-cyanopyrazine by the action of ethanol (or methanol) in the presence of triethylamine (985). 2-Cyanopyrazine treated in water with hydroxylamine hydrochloride and sodium carbonate at 70-75° gave 2-(C-amino-C-hydroxyiminomethyl)-pyrazine (62), and 2aluminum chloride at 140-220° gave 2-(C-anilino-C-iminomethyl)pyrazine (and similar preparations were carried out with other aromatic amines) (1334,1410). 

Chloro-6-cyanopyrazine with aqueous methylamine at 0° gave 2-chloro-6-(A -methylamidino)pyrazine (940), and 2-cyano-6-dimethylaminopyrazine with dimethylamine in the presence of anhydrous aluminum chloride gave 2-dimethyl-amino-6-(C-dimethylamino-C-iminomethyl)pyrazine and similar reactions were observed with other secondary amines (1424). 

Although there have been few new developments in the period since 1993, halogenopyrazines 42 have been convenient precursors for a variety of pyrazine derivatives. For example, the halogenopyrazines 42 are cyanated by palladium-catalyzed cross-coupling with alkali cyanide or by treatment with copper cyanide in refluxing picoline, to yield cyanopyrazines 48. Alkoxypyrazines 49 are produced by treatment with alkoxide-alcohol, and aminopyrazines 50 are prepared by amination with ammonia or appropriate amines. The nucleophilic substitution of chloropyrazine with sodium alkoxide, phenoxide, alkyl- or arylthiolate is efficiently effected under focused microwave irradiation <2002T887>. 

Cyanopyrazines react with aromatic amines in the presence of aluminum chloride as catalyst at temperatures below 200° and give amidine derivatives in good yield [Eq. (14)].228 Hydrogenation of... 

The replacement of nitrile groups by amino groups is exemplified by the reaction of 2,3-dicyano-pyrazine (272) with an aqueous solution of methyl-amine to give 3-methylamino-2-cyanopyrazine (273) (86JHC1299 see also... 

Condensation of 2-amino-5-bromomethyl-3-cyanopyrazine 1-oxides with the appropriate substituted amine afforded a series of 2-amino-5-([(aryl and aralkyl)-amino]methyl -3-cyanopyrazine 1-oxides (1040), and with p-chlorophenol and arylthiols gave 2-amino-5-[(p-chlorophenoxy)methyl]-3-cyanopyrazine 1-oxide and 2-amino-5[(arylthio)methyl]-3-cyanopyrazine 1-oxides (1041). 

Amine substitution of activated halogeno or other groups on pyrazines and quinoxalines has been described (Section 6.03.5.4.2). It is noteworthy that a variety of 2-amino-3-cyanopyrazines are produced by reaction of 2-cyano-3-phenylsulfonylpyrazine with the corresponding amines (Equation (6)). 

A -formyl group. Subsequently, dl-(VIII.64) was prepared by a modified Taylor synthesis by Rosowsky et al. [265], 4-(7V-Methyl-A -tosylamino)benzoyl chloride was condensed with diethyl DL-3-aminoglutarate, the tosyl group was removed with HBr, the resultant amine was coupled to 2-amino-5-chlorome-thyl-3-cyanopyrazine A -oxide [24], and the 7V-oxide was directly reduced to amino nitrile dl-(VIII.66) with triethyl phosphite and condensed with guanidine carbonate to form diester dl-(VIII.64) in low yield. 

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