The condensation of ethyl cyanopyruvate (I) with 2-fluorobenzyl hydrazine (II) in the presence of trifluoroacetic acid produced the aminopyrazole (III). This was further condensed with (dimethylamino)acrolein (IV) under acidic conditions to furnish the pyrazolopyridine (V). The ethyl ester group of (V) was then converted to nitrile (VII) via formation of the corresponding amide (VI), followed by dehydration with trifluoroacetic anhydride. Addition of methoxide to the cyano group of (VII) produced imidate (VIII), which was treated with ammonium chloride to yield the amidine (IX).

Condensation of cyclopropaneacetonitrile (X) with bis(dimethylamino)-tert-butoxymethane gave rise to the enamino nitrile (XI). This was then cyclized with amidine (IX) to produce the target pyrimidine derivative.

The condensation of ethyl cyanopyruvate (I) with 2-fluorobenzyl hydrazine (II) in the presence of trifluoroacetic acid produced the aminopyrazole (III). This was further condensed with (dimethylamino)acrolein (IV) under acidic conditions to furnish the pyrazolopyridine (V). The ethyl ester group of (V) was then converted to nitrile (VII) via formation of the corresponding amide (VI), followed by dehydration with trifluoroacetic anhydride. Addition of methoxide to the cyano group of (VII) produced imidate (VIII), which was treated with ammonium chloride to yield the amidine (IX).

In a related method, Claisen condensation of ethyl formate with cyclopropaneacetonitrile (X), followed by acetylation of the intermediate potassium enolate (XII) with Ac2O, furnished the (acetoxy)acrylonitrile (XIII). This was finally cyclized with amidine (IX) in the presence of Et3N in refluxing toluene.

The condensation of ethyl cyanopyruvate (I) with 2-fluorobenzyl hydrazine (II) in the presence of trifluoroacetic acid produced the aminopyrazole (III). This was further condensed with (dimethylamino)acrolein (IV) under acidic conditions to furnish the pyrazolopyridine (V). The ethyl ester group of (V) was then converted to nitrile (VII) via formation of the corresponding amide (VI), followed by dehydration with trifluoroacetic anhydride. Addition of methoxide to the cyano group of (VII) produced imidate (VIII), which was treated with ammonium chloride to yield the amidine (IX).

Condensation of cyclopropaneacetonitrile (X) with bis(dimethylamino)-tert-butoxymethane gave rise to the enamino nitrile (XI). This was then cyclized with amidine (IX) to produce the target pyrimidine derivative.

The condensation between 2-fluorobenzylhydrazine (I) and the sodium enolate of ethyl cyanopyruvate (II) in the presence of trifluoroacetic acid produced the pyrazole derivative (III). Subsequent cyclization of aminopyrazole (III) with (dimethylamino)acrolein (IV) gave the pyrazolopyridine (V). Amonolysis of the ethyl ester group of (V) afforded amide (VI), which was further dehydrated to nitrile (VII) by means of trifluoroacetic anhydride and pyridine. Addition of sodium methoxide to nitrile (VII) furnished imidate (VIII). This was converted to the corresponding amidine (IX) upon treatment with ammonium chloride and HOAc. Finally, the title diamino pyrimidine compound was obtained by heating a mixture of amidine (IX) and morpholinomalononitrile (X).

The reaction of 2-cyclopropylacetonitrile (I) with ethyl formate (II) by means of t-BuOK in THF gives the hydroxymethylene derivative (III), which is cyclized with 1-(2-fluorobenzyl)pyrazolo[3,4-b]pyridine-3-carboxamidine (IV)(see scheme no. 28591301a, intermediate (IX)) by heating at 105 C to afford the target aminopyrimidine derivative.