2.6- Diamino-3,5-dicyanopyrazine

The direct alkylation of aminopyrazines is usually unsatisfactory as a synthetic method because it mainly takes place at the most basic ring nitrogen. However, 3,6-diamino-2,5-dicyanopyrazines are successfully alkylated by treatment with alkyl iodide or bromide in protic solvent in the presence of alkali such as NaOH in dimethylacetamide (DMA) to form bis(dialkylamino)pyrazines <1998DP(39)49>. Reaction of 2,6-diamino-3,5-diarylpyrazine with methylglyoxal in aqueous HCl-ethanol led to -alkylation but no formation of the expected bicyclic imidazolo[l,2- z]pyrazine <2001S768>. 

Treatment of 2-amino-3,5,6-tricyanopyrazine (57), prepared in 95% yield by condensation of DISN and DAMN (Section V,A,2,b), with ammonia under very mild conditions gives 2,6-diamino-3,5-dicyanopyrazine (58) in nearly quantitative yield (74USP3814757). The regiochemistry of the displacement was determined by hydrolysis to 2,6-diamino-3,5-dicarboxypyrazine (85),... 

The use of a, -diaminopropionic acid with a,0-dicarbonyl compoimds leads to pyrazinecarboxylic acids (351, 352), and diaminomaleonitrile (S3) gives 2,3-dicyanopyrazines (52, R = R = CN) (353, 355, 357). The condensation of a,/3-diamino compounds with a-keto esters has been shown to give 5-hydroxy-23-dihydropyrazines (51, R = OH) (340). 

Tetracyanopyrazine has been reported to react with liquid ammonia in tetra-hydrofuran to give 2,6-diamino-3,5-dicyanopyrazine (1180, 1182), and with dimethylamine in tetrahydrofuran at 0° to give 2,3,5-tricyano-6-dimethylamino-pyrazine (97.7%) (158), and this on treatment with ammonia in tetrahydrofuran gave 2-amino-3,5-dicyano-6-dimethylaminopyrazine (89%) (158). 

Tetracyanopyrazine with liquid ammonia in tetrahydrofuran formed 2,6-diamino-3,5-dicyanopyrazine (1180, 1182), and tetracyanopyrazine with piperazine similarly gave 2,6-dicyano-3,5-dipiperazin-l -ylpyrazine (1182). 

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