The synthesis and some properties of 1-(2-amino-oxyethyl)cytosines

Abstract

1-(2-Amino-oxyethyl)cytosine (III) has been prepared from 4-methylthio-1-(2-phthalimido-oxyethyl)-pyrimidin-2(1H)-one (II) and methanolic ammonia. Methylation of a protected derivative of N(4)-acetyl-(III) with diazomethane gave the 3- and N(4)-methyl derivatives (VIII) and (IV) of compound (III). In deuterium oxide at pD 6·4 the C-5 proton in (III), and that in (VIII), is rapidly replaced by deuterium. Compound (III) in aqueous hydroxylamine (pH 6) undergoes rapid ring closure at C-6 and substitution by hydroxylamine at C-4 to give 1,3,4,8,9,9a-hexahydro-8-hydroxyiminopyrimido[4,3-c][1,2,4]oxadiazin-6(7H)-one (XI). Compound (III) also undergoes self-condensation to give a ‘dimeric’ product of structure analogous to (XI).

A possibly general method for the synthesis of alkoxyamines by cleavage of N-alkoxyphthalimides with methanolic ammonia is discussed.