Alkylation of methyl 4-oxo-3-piperidinecarboxylate (I) with ethyl bromoacetate provided piperidineacetate (II). Subsequent decarbomethoxylation of (II) using LiCl in boiling DMF produced piperidone (III). On the other hand, coupling between 4-aminobenzonitrile (IV) and N-Boc-glycine (V) via activation with carbonyldiimidazole gave amide (V). The Boc group of (V) was then deprotected with HCl in EtOAc to yield 2-amino-N-(4-cyanophenyl)acetamide (VI). Reductive condensation of amine (VI) with piperidone (III) employing NaBH(OAc)3 furnished adduct (VII), which was further reductocondensed with chloroacetaldehyde to give chloroethyl amine (VIII). Cyclization of (VIII) in the presence of NaH generated piperazinone (IX). Finally, addition of hydroxylamine to the cyano group of (IX) provided the corresponding hydroxyamidine.

Alkylation of methyl 4-oxo-3-piperidinecarboxylate (I) with ethyl bromoacetate provided piperidineacetate (II). Subsequent decarbomethoxylation of (II) using LiCl in boiling DMF produced piperidone (III). On the other hand, coupling between 4-aminobenzonitrile (IV) and N-Boc-glycine (V) via activation with carbonyldiimidazole gave amide (V). The Boc group of (V) was then deprotected with HCl in EtOAc to yield 2-amino-N-(4-cyanophenyl)acetamide (VI). Reductive condensation of amine (VI) with piperidone (III) employing NaBH(OAc)3 furnished adduct (VII), which was further reductocondensed with chloroacetaldehyde to give chloroethyl amine (VIII). Cyclization of (VIII) in the presence of NaH generated piperazinone (IX). Finally, addition of hydroxylamine to the cyano group of (IX) provided the corresponding hydroxyamidine.