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