Ammonia → 2-[benzothiazol-2(3H)-ylidene]-2-cyanoacetamidine

Participants

Reaction Steps

In the first step, the benzothiazole 10 [L is a leaving group, as in Reaction Scheme 4] reacts with malononitrile in the presence of a strong base, such as sodium ethoxide in ethanol, to give the 2-[benzothiazol-2(3H)-ylidene]malononitrile 17. Reaction of this nitrile in suspension in a polar solvent with gaseous hydrogen chloride gives the 2-[benzothiazol-2(3H)-ylidene]-2-cyanoacetimidate 18, and reaction of the imidate with ammonia gives the corresponding 2-[benzothiazol-2(3H)-ylidene]-2-cyanoacetamidine 19. Compound 19 is then reacted with a β-diketone or equivalent, such as 2,4-pentanedione or ethyl 3-oxo-4,4,4-trifluorobutyrate, to form the pyrimidine ring [substituents not shown] of the compound of formula 6, in the presence of a base such as sodium ethoxide in an aprotic solvent under strong (e.g. microwave) heating. Finally, the compound of formula 6 is hydrolyzed to a compound of formula 8, as in Reaction Scheme 1. If the order is reversed, so that the hydrolysis is performed before the coupling, the hydrolysis proceeds as in Reaction Scheme 1, and the coupling may take place under milder conditions.

Provenance & Evidence