Methanol → Pyrazine-2-carboxamidine hydrochloride

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Reaction Steps

According to Scheme 1, step a, pyrazine-2-carbonitrile 1 is reacted in an alcohol solvent, preferably methyl alcohol in the presence of base A selected from an alkali metal hydroxide or alkali metal alkoxide, preferably sodium methoxide and more preferably sodium methoxide in a ratio of about 1:1 (mole/mole) in the temperature range of about 20-40° C., preferably in the range of about 28-32° C. for about 3-12 h, preferably in the range of 4-5 h, followed by treating with an ammonium salt of an inorganic acid, for example, ammonium chloride for a period of about 16-48 h, preferably in the range of 20-24 h at about 25° C. or optionally for about 3-6 h at reflux. Methyl t-butyl ether is added and the mixture is stirred for about 15 to 30 min and the solid which forms is collected by filtration, washed with methyl t-butyl ether then dried at about 40° C. under vacuum to give pyrazine-2-carboxamidine hydrochloride 2 as a white solid. Optionally following reflux the volatiles are removed to a residue and the residue is crystallized from ethanol-diethyl ether and the product collected. In particular, the procedure described has higher yields as compared to the art (S. Kushner et al, J. Amer. Chem. Soc., 74, 3617-3621 (1952) and published patent application US2005-0075357A1).

Provenance & Evidence