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Diuretic

A nitrogen substituent on a pyrazine ring carbon is often introduced by displacement of chloride. The substitution is facilitated by the adjacent ring nitrogen and can be further facilitated by an electron‐withdrawing group (NO ₂ , SO ₂ R, COOR, CN) on a para ring carbon.

Discussion. The guanidine group is introduced in the final step by reaction of guanidine with the methyl ester. Chloride at the 5‐position of the 5,6‐dichloropyrazine is displaced by ammonia. The 5,6‐dichloropyrazine is formed by chlorination of methyl 3‐aminopyrazine‐2‐carboxylate. The methyl ester is formed from the carboxylic acid (Fischer Esterification).

3‐Aminopyrazine‐2‐carboxylic acid is formed by hydrolysis of the pyrimidine ring of lumazine (1H‐pteridine‐2,4‐dione). The pyrazine ring of lumazine is formed by reaction of 5,6‐diaminouracil with glyoxal. The amino group at the 5‐position of 5,6‐diaminouracil is formed by reduction of a nitroso group. The nitroso group is introduced by nitrosation of 6‐aminouracil. 6‐Aminouracil is formed from ethyl cyanoacetate and urea.