The cyclization of ethyl cyanoacetate (I) with urea (II) in ethanolic NaOEt provided 6-aminouracil (III). Nitrosation of (III) with NaNO2 in aqueous AcOH, followed by reduction of the resulting nitroso compound (IV) using sodium hydrosulfite gave 5,6-diaminouracil, which was purified by conversion to its hydrochloride salt (V). Condensation of this diamine with melted oxalic acid produced tetrahydroxypteridine (VI). Subsequent reaction of (VI) with PCl5 and POCl3 afforded tetrachlorocompound (VII). The reaction of (VII) with pyrrolidine (VIII) in aqueous KHCO3/CHCl3 resulted in a mixture of 2-, 4-, 7- and 4,7-substituted compounds, from which the desired 4-pyrrolidino-2,6,7-trichloropteridine (IX) was isolated by column chromatography. Further treatment of (IX) with benzylamine (X) in dioxan at r.t. provided diamine (XI). Finally, substitution of the third chlorine atom for piperazine (XII) was accomplished in boiling dioxan.

The cyclization of ethyl cyanoacetate (I) with urea (II) in ethanolic NaOEt provided 6-aminouracil (III). Nitrosation of (III) with NaNO2 in aqueous AcOH, followed by reduction of the resulting nitroso compound (IV) using sodium hydrosulfite gave 5,6-diaminouracil, which was purified by conversion to its hydrochloride salt (V). Condensation of this diamine with melted oxalic acid produced tetrahydroxypteridine (VI). Subsequent reaction of (VI) with PCl5 and POCl3 afforded tetrachlorocompound (VII). The reaction of (VII) with pyrrolidine (VIII) in aqueous KHCO3/CHCl3 resulted in a mixture of 2-, 4-, 7- and 4,7-substituted compounds, from which the desired 4-pyrrolidino-2,6,7-trichloropteridine (IX) was isolated by column chromatography. Further treatment of (IX) with benzylamine (X) in dioxan at r.t. provided diamine (XI). Finally, substitution of the third chlorine atom for piperazine (XII) was accomplished in boiling dioxan.

The cyclization of ethyl cyanoacetate (I) with urea (II) in ethanolic NaOEt provided 6-aminouracil (III). Nitrosation of (III) with NaNO2 in aqueous AcOH, followed by reduction of the resulting nitroso compound (IV) using sodium hydrosulfite gave 5,6-diaminouracil, which was purified by conversion to its hydrochloride salt (V). Condensation of this diamine with melted oxalic acid produced tetrahydroxypteridine (VI). Subsequent reaction of (VI) with PCl5 and POCl3 afforded tetrachlorocompound (VII). The reaction of (VII) with pyrrolidine (VIII) in aqueous KHCO3/CHCl3 resulted in a mixture of 2-, 4-, 7- and 4,7-substituted compounds, from which the desired 4-pyrrolidino-2,6,7-trichloropteridine (IX) was isolated by column chromatography. Further treatment of (IX) with benzylamine (X) in dioxan at r.t. provided diamine (XI). Finally, substitution of the third chlorine atom for piperazine (XII) was accomplished in boiling dioxan.