Journal of Labelled Compounds and Radiopharmaceuticals
J Label Compd Radiopharm 2007; 50: 576–577.
Published online in Wiley InterScience
JLCR
Short Research Article
Synthesis of 1-(1-benzyl-2-ethylthio-2-14C-5-imidazolyl)-
4-{3-(1-isopropylamino)-2-pridyl} piperaziney
NADER SAEMIAN*, GHOLAMHOSSEIN SHIRVANI and HOJATOLLAH MATLOUBI
Nuclear Research Center/AEOI, Chemical Division, P.O. Box 11365-3486, Tehran, Iran
Received 21 June 2006; Revised 22 January 2007; Accepted 23 January 2007
Keywords: carbon-14; bis(heteroaryl) piperazines
Introduction
Results and discussion
A variety of analogues of bis (heteroaryl) piperazines
(BHAPs) (such as: U-80493E) were synthesized and
evaluated for their inhibition of human immuodefi-
ciency virus type1 (HIV-1) reverse transcriptase.1
Sometimes replacement of the substituted aryl moiety
with other various aromatic systems provided bis
(heteroaryl) piperazines that were 10–100 fold more
potent than U-80493E (for instance: Atevirdine).2
According to previous structure and activity relation-
ship studies on atevirdine, the compound 1 was
synthesized by Hadizadeh and coworkers, in which
1-(3-alkylamino-2-pyridyl) piperazine part of the mole-
cule was unchanged and 5-alkoxy-2-indolylcarbonyl
part of the molecule was replaced by benzyl-
2-alkylthio-imidazolylcarbonyl moiety.3 Therefore, to
further elucidate the mechanism of action and to
support ongoing metabolism studies, there arose a
need for analogs of this compound carbon-14 labelled
in a biologically stable site.4 In this paper, the synthesis
In this approach, according to the synthetic pathway
shown in Scheme 1, barium [14C]carbonate 2 was
converted to potassium [14C]cyanide 3 according to
standard procedure.5
Then potassium [14C]thiocyanate 4 was obtained
quantitatively via the reaction between potassium [14C]
cyanide 3 and sulfur in acetone.6 Potassium [14C]
thiocyanate 4 was stirred with 1,3-dihydroxyacetone
dimmer 6 and benzylamine hydrochloride 5 to give
[2-14C]-5-hydroxymethyl-2-mercapto-1-benzylimidazole
7.7 Subsequent alkylation of compound 7 with ethyl
iodide and oxidation of the product with manganese
dioxide and further oxidation of the latter product with
alkaline solution of silver nitrate gave [2-14C]-2-
ethylthio-1-benzylimidazole-5-carboxylic acid 8.8–10
On the other hand, 1-[ 3-(1-isopropylamino)-2-pridyl]
piperazine 13 has been synthesized as part of a 4-step
sequence from piperazine 11 and 2-chloro-3-nitro
pyridine 12.1 The final step coupling of 8 with 13
was accomplished utilizing 1,10-sulfinyldiimidazole
to afford the title compound 1-(1-benzyl-2-ethylthio-
2-[14C]-5-imidazolyl)-4-{3-(1-isopropylamino)-2-pridyl}
piperazine 1.
of
1-(1-benzyl-2-ethylthio-2-[14C]-5-imidazolyl)-4-{3-
(1-isopropylamino)-2-pridyl} piperazine 1 is described.
RHN
N
Et
N
N
S
N
N
O
Bn
1
R:isopropyl
*Correspondence to: Nader Saemian, Nuclear Research Center/AEOI,
Chemical Division, P.O. Box 11365-3486, Tehran, Iran.
E-mail: nsaemian@aeoi.org.ir
yProceedings of the Ninth International Symposium on the Synthesis
and Applications of Isotopically Labelled Compounds, Edinburgh,
16–20 July 2006.
Copyright # 2007 John Wiley & Sons, Ltd.