Russian Journal of Applied Chemistry, 2013, Vol. 86, No. 7, pp. 1088−1089.
Pleiades Publishing, Ltd., 2013.
Original Russian Text © N.A. Tankabekyan, V.M. Mokhov, Yu.V. Popov, 2013, published in Zhurnal Prikladnoi Khimii, 2013, Vol. 86, No. 7, pp. 1156−1157.
Alkylation of Saturated Nitrogen-containing Heterocycles
N. A. Tankabekyan, V. M. Mokhov, and Yu. V. Popov
Volgograd State Technical University, Volgograd, Russia
Received May 16, 2013
Abstract—A synthetic route toward 1-N-heteryl-4-oxoadamantanes, intermediates in the synthesis of 1-heteryl-4-
(R)-amino(acylamino)adamantanes used for treating type II diabetes and other diseases, was developed. Synthesis
of 1-N-heteryl-4-oxoadamantanes was carried out by alkylation of saturated nitrogen-containing heterocycles with
Derivatives of 1,4-dialkylamino(diacylamino)
adamantane are used for treatment of type II diabetes
and metabolic syndrome, as well as for treatment and
prevention of various immunopathological, in particular
autoimmune, inﬂ ammatory, and allergic, diseases [1–5].
Promising starting compounds for their synthesis are
1-heteryl-4-(R)-amino(acylamino)adamantanes [2, 3].
The aim of this study was to ﬁ nd routes for direct
and selective introduction of a nitrogen-containing
moiety into the 1-position of the adamantane core, while
retaining the 4-position of the carbonyl group which is
readily further functionalized to a substituted amino
group . The starting compound was synthetically
available 1-bromo-4-oxoadamantane I . There exist
published data on alkylation of saturated nitrogen-
containing heterocycles with 1-bromoadamantane ,
but data on the use of compound I in this reaction are
To obtain 1-N-heteryl-4-oxoadamantanes IIIa–IIIc,
we studied for the ﬁ rst time the reaction of alkylation of
heterocycles from the piperidine (IIa), morpholine (IIb),
and piperazine (IIc) series with compound I:
The reaction was carried out at the reactant molar
ratio I : (IIa–IIc) = 1 : (3–4) in a sealed ampule at
190–220°C in the course of 7–8 h. After isolation and
puriﬁ cation, the yield of products IIIa–IIIc was 50–54%.
It was found that, compared to 1-bromoadamantane,
compound I is less reactive toward IIa–IIc, due to the