2-Cyano-3-methoxypyrazine

The primary synthesis of 2-cyano-3-methoxypyrazines was completed by a sequence of reactions starting from aminomalononitrile (Scheme 40). 

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-... 

Dicyano-3,6-dimethylpyrazine shaken with sodium ethoxide at room temperature for 10 hours produced 2-cyano-5-ethoxy-3,6-dimethylpyrazine (288). Bromination of 2-methoxy-3-sulfanilamidopyrazine (39) in methanol led to 5-(4 -amino-3, 5 -dibromobenzenesulfonimido)-6-hydroxy-2,3-dimethoxy-2,3,4,5-tetrahydropyrazine (32) which with 2 N sodium hydroxide gave 3-(4 -amino-3, 5 -dibromobenzenesulfonamido)-2-hydroxy-5 nethoxypyrazine (40) (816). The preparation of 2-amino-3,5-dicyano-6-methoxy(and ethoxy)pyrazine from a-(p-toluenesulfonyloxyiminomalononitrile and malononitrile has been described in Section II.7 (484). 2-Methoxycarbonyl(and cyano)-5-pyridiniopyrazine chloride (41) is reported (conditions not stated) to give 2-carboxy(and carbamoyl)-5-methoxypyrazine (765). 

Alkoxypyrazine A-oxides may also be prepared by oxidation of the alkoxypyrazine with peroxyacetic acid. In this way the following have been prepared 3-ethoxypyrazine 1-oxide (100°/20h) (978) 3-(trideuteromethoxy)pyrazine 1-oxide (757l9h) (975) 3-ethoxy-2-methylpyrazine 1-oxide (65-75724h) (978) 3-methoxy-2-phenylpyrazine 1-oxide (55720 h) (817) 3-ethoxy-2,5-dimethyl-pyrazine 1-oxide (56716 h) (872) 3-carbamoyl-2-methoxypyrazine 1-oxide (80720h) (881) and 2-cyano-5-ethoxy-3,6-dimethylpyrazine A-oxide (55720h) (288). 

The use of a carboximidate to yield a 4-methoxypteridine is illustrated by the synthesis of 4,7-dimethoxypteridine-6-carbonitrile (5) from methyl 3-amino-6-cyano-5-methoxypyrazine-2-carboximidate (4).141... 

---