Efficient synthesis of S-dipeptidothiouracil derivatives via a one-pot, five-component reaction under ionic liquid condition

Article abstract of DOI:10.1080/17415993.2012.662982

S-Dipeptidothiouracil derivatives were successfully synthesized via a one-pot, five-component nucleophilic addition/Ugi reaction sequence under ionic liquid conditions at room temperature. Simplicity, green condition, and high yields of products are advantages of this method.

Full text of DOI:10.1080/17415993.2012.662982

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Efficient synthesis of S-
dipeptidothiouracil derivatives via
a one-pot, five-component reaction
under ionic liquid condition
Ashraf Sadat Shahvelayati a & Zohreh Esmaeeli a
a Department of Chemistry, Shahr-e Rey Branch, Islamic Azad
University, Tehran, Iran
Published online: 04 Apr 2012.
To cite this article: Ashraf Sadat Shahvelayati & Zohreh Esmaeeli (2012) Efficient synthesis of S-
dipeptidothiouracil derivatives via a one-pot, five-component reaction under ionic liquid condition,
Journal of Sulfur Chemistry, 33:3, 319-325, DOI: 10.1080/17415993.2012.662982
To link to this article: http://dx.doi.org/10.1080/17415993.2012.662982
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Journal of Sulfur Chemistry
Vol. 33, No. 3, June 2012, 319–325
Efficient synthesis of S-dipeptidothiouracil derivatives via a
one-pot, five-component reaction under ionic liquid condition
Ashraf Sadat Shahvelayati* and Zohreh Esmaeeli
Department of Chemistry, Shahr-e Rey Branch, Islamic Azad University, Tehran, Iran
(Received 27 December 2011; final version received 30 January 2012)
S-Dipeptidothiouracil derivatives were successfully synthesized via a one-pot, five-component nucle-
ophilic addition/Ugi reaction sequence under ionic liquid conditions at room temperature. Simplicity,
green condition, and high yields of products are advantages of this method.
R1
H
H
ClC 2COO
O
NH2
R
R
O
H
N
1
3
N
S
H
il
r.t.
O
N
R2
N
R
S
NH
4
R1
NH
R
R2
N
C
6
O
2
O
5
10 Examples 62-90% Yield
Keywords: thiouracil; one-pot; nucleophilic addition; Ugi reaction; five-component reaction; ionic liquid
1. Introduction
Two very important classes of natural products, pyrimidine bases and pseudopeptides, play
important roles in various biological systems. Thio derivatives of pyrimidine bases includ-
ing 2-thiouracil, 4-propyl-2-thiouracil, and 2-thiocytosine are minor components of t-RNA and
furthermore, they have contributed remarkably to biological, pharmacological and medicinal
chemistry. Their S-, N-, or S, N-disubstituted analogs have shown therapeutic properties, espe-
cially antiviral, antithyroid, and antitumor activities. They have also been reported as biosensors
and radio protectors. The prototropic tautomerism of thio derivatives of pyrimidine bases has
attracted much attention. The tautomeric equilibrium of 2-thiouracil determines its chemoselec-
tivity and regioselectivity, and is dependent on the temperature and on whether it is in the solution
or in the solid state (1–3).
*Corresponding author. Email: avelayati@yahoo.com
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2012 Taylor & Francis
http://dx.doi.org/10.1080/17415993.2012.662982
http://www.tandfonline.com

320 A.S. Shahvelayati and Z. Esmaeeli
In this field, multicomponent condensation reactions based on isocyanides have been utilized
efficiently in conjunction with combinatorial chemistry to prepare polyfunctional compounds
in short reaction sequences (4, 5). One of the best-known multicomponent reactions is the Ugi
four-component reaction (4CR) which occurs in good yields (6). In this reaction, an isocyanide,
an amine, a carboxylic acid, and an oxo compound are spontaneously condensed to yield an
acylaminocarboxamide. Generally, the Ugi 4CRs were performed in organic solvents such as
methanol or tetrahydrofuran at room temperature for 1–2 days (7). Recently, new solvents not
previously utilized such as water (8) or ionic liquids (9) have been used for these reactions.
Room-temperature ionic liquids (RTILs), especially those based on 1,3-dialkylimidazolium
salts, have shown great promise as attractive alternatives to the conventional solvents.They possess
the unique advantages of high thermal stability, negligible vapor pressure, immiscibility with both
organic compounds and water, and recyclability (10–12).
2. Results and discussion
As part of our current study on the development of new routes to the synthesis of organosulfur com-
pounds(13–15), wereporthereanefficientand convenient procedureforthesynthesisof thiouracil
derivatives under ionic liquid conditions at room temperature. Thus a one-pot, five-component
reaction consisting of chloroacetic acid (1), 4-propyl-2-thiouracil (2), primary amines (3), oxo
compound (4), and isocyanides (5) leads to the pseudopeptidothiouracil derivatives as shown in
Scheme 1. The connection of a dipeptide moiety to the thiouracil derivatives in 6a–6j (Scheme 2)
is an interesting structural feature that might increase pharmacological and biological activities
of these compounds.
The structures of compounds 6a–6j were verified by IR, 1H NMR, and 13C NMR spectral data.
The mass spectra of compounds 6a–6j displayed molecular ion peaks at appropriate m/z-values.
1
The IR and H NMR spectra of 6a–6j exhibited two characteristic peaks for the NH groups.
13
=
The proton-decoupled C NMR spectra of 6a–6j showed three distinct resonances for C O
groups. For example, the 1H NMR spectrum of 6c in CDCl3 showed a doublet (δ = 5.70 ppm)
and a singlet (δ = 8.52 ppm) for the NH groups. The methyl protons in 6c appeared as a triplet
(δ = 0.93 ppm) and a singlet (δ = 1.49 ppm). The methylene protons of n-propyl group in 6c
appeared as a multiplet (δ = 1.54–1.63 ppm) and a triplet (δ = 2.39 ppm), and the protons of
SCH2 and NCH2 moieties exhibited two singlets at δ = 3.95 and 4.82 ppm, respectively. The
vinyl proton on the thiouracil ring appeared as a singlet at δ = 5.99 ppm and characteristic signals
for the cyclohexyl and phenyl groups were also observed. The 1H-decoupled 13C NMR spectrum
of 6c showed 21 signals which is in agreement with the proposed structure including three distinct
R1
H
NH2
N
S
N
O
H
COO
R2
S
3
il
r.t.
O
H
H
ClC 2COO
R
NH
NH
1
4
2
R
O
N
C
O
R
R
H
5
N
N
S
il
R2
N
r.t.
NH
O
R1
6
O
Scheme 1. Synthesis of S-thiouracil derivatives via a five-component reaction.

Journal of Sulfur Chemistry 321
O
O
H
H
O
H
N
N
O
N
N
O
S
S
N
O
N
S
N
N
N
NH
O
NH
O
NH
O
a
6
c
6
6b
O
H
O
O
N
H
N
O
S
H
N
N
O
N
O
N
S
N
S
N
N
NH
O
NH
NH
O
O
6f
e
6
6d
O
O
H
H
N
O
N
N
N
S
S
O
H
N
N
N
N
S
NH
O
NH
O
N
O
NH
O
6i
6g
h
6
O
O
H
N
O
N
S
N
NH
O
6j
Scheme 2. Chemical structures of S-thiouracil derivatives 6a–6j.
=
resonances for the C O groups. Partial assignments of aromatic and cyclohexyl resonances are
given in Section 4. The mass spectrum of 6c displayed the molecular ion peak at m/z = 484.
The advantage of the present procedure is that all five starting materials were mixed in a one-pot
reaction without any catalyst and without the need for separation of intermediates. A tentative
mechanism for this transformation is proposed in Scheme 3. Presumably, the reaction proceeds
step by step to generate the intermediate 7, which would then undergo acyl transfer reaction (the
Mumm rearrangment) to produce final products.
H
N
S
l H
C C 2COO
H
HN
1
2
O
il
N
OOC
N
S
R1
H
N
O
OOC
S
il
NH2
HN
3
N
R1
R2
HN
C
O
O
H
O
R
5
R
R
4
R
N
R
R1
R
R1
R
R
H
N
N
HN
R
O
N
O
S
N
R2
R
NH
O
S
NH
O
R1
N
O
R2
6
7
Scheme 3. Proposed mechanism for the formation of compounds 6.

322 A.S. Shahvelayati and Z. Esmaeeli
3. Conclusions
In conclusion, we have described an efficient method for the synthesis of S-dipeptidothiouracil
derivatives in high yields, via a one-pot, five-component reaction using an ionic liquid as a
new solvent. Reaction times were dramatically reduced, and yields were generally improved by
this new method. The reaction scope is broad, which permits the use of three points of diver-
sity in the starting materials. Due to the well-recognized utility of thiouracil derivatives, many
libraries of compounds can be prepared using this method as structural scaffolds for further
diversification.
4. Experimental
4.1. General
Chloroacetic acid, 4-propylthiouracil, amines, alkylisocyanides, and ketones were obtained from
Merck and were used without further purification. [bmim]Br was synthesized from the reaction of
N-methylimidazole and n-butyl bromide (16). Melting points were obtained uncorrected using an
Electrothermal-9100 apparatus. IR spectra were recorded with a Shimadzu IR-460 spectrometer.
1H and 13C NMR spectra were recorded with a Bruker DRX-300Avance instrument using CDCl3
as the deuterated solvent containing tetramethylsilane as internal standard, at 300 and 75 MHz,
respectively, in parts per million, and J in hertz. Electron impact ionization-mass spectroscopy
(EI-MS) (70 eV): mass spectra were obtained with a Finnigan-MAT-8430 mass spectrometer (in
m/z). Elemental analyses (C, H, N) were obtained with a Heraeus CHN-O-Rapid analyzer.
4.2. General procedure for the synthesis of thiouracil derivatives 6a–6j
4-Propyl thiouracil (2) (1 mmol) was added to chloroacetic acid (1) (1 mmol) in 1 ml of [bmim]Br
and the mixture was stirred at room temperature for 0.5 h. Then, primary amine 3 (1 mmol) and
oxo compound 4 (1.2 mmol) were added and stirred for 15 min, and is followed by addition
of isocyanide 5 (1 mmol). The reaction was detected by TLC (n-hexane–EtOAc, 3/1) and was
completed after 5 h. The residue was dissolved in diluted NaHCO3 (30 ml) and the mixture was
extracted with AcOEt (2 × 15 ml) and was dried on Na2SO4. The solvent was evaporated under
reduced pressure to leave a residue that was dried by column chromatography [silica gel (230–400
mesh; Merck), hexane/AcOEt, 3:1] to afford desired pure products 6a–6j.
4.2.1. N-Cyclohexyl-2-(N-ethyl-2-((6-oxo-4-propyl-1,6-dihydropyrimidin-2-
yl)thio)acetamido)-2-methyl propanamide (6a)
White powder, m.p. 89–90 ◦C; yield: 0.35 g (83%). IR (KBr): 3342, 3321, 1646, 1576, 1570 cm−1
.
1H NMR: δ = 0.95 (3H, t, 3J = 7.3 Hz, Me), 1.01–1.90 (10H, m, 5CH2), 1.34 (3H, t, 3J = 7.0 Hz,
Me), 1.50 (6H, s, 2Me), 1.62–1.70 (2H, m, CH2), 2.49 (2H, t, 3J = 7.3 Hz, CH2), 3.61–3.76 (1H,
3
3
m, CH), 3.65 (2H, q, J = 7.0 Hz, CH2), 4.10 (2H, s, SCH2), 5.58 (1H, d, J = 8.0 Hz, NH),
6.02 (1H, s, CH), 7.10 (1H, br s, NH). 13C NMR: δ = 13.8 (Me), 16.7 (Me), 21.4 (CH2), 24.6
(CH2), 24.9 (2 Me), 25.4 (2CH2), 32.6 (2CH2), 33.6 (CH2), 39.3 (CH2), 39.6 (CH), 48.3 (CH2),
=
=
=
62.6 (C), 107.1 (C), 155.0 (CH), 160.0 (C), 162.6 (C O), 169.6 (C O), 173.9 (C O). EI-MS:
m/z (%) = 422 (M+, 2.5), 211 (28), 169 (15), 125 (21), 97 (45), 57 (33), 43 (27), 29 (18). Anal.
Calcd for C21H34N4O3S (422.58): C, 59.69; H, 8.11; N, 13.26; Found: C, 59.95; H, 8.58; N,
13.11%.

Journal of Sulfur Chemistry 323
4.2.2. N-Benzyl-2-((6-oxo-4-propyl-1,6-dihydropyrimidin-2-yl)thio)acetamido-N-
cyclohexyl-2-ethylbutanamide (6b)
White powder, m.p. 77–80 ◦C; yield: 0.40 g (78%). IR (KBr): 3286, 3064, 1677, 1665, 1570 cm−1
.
3
3
1H NMR: δ = 0.90 (6H, t, J = 7.1 Hz, 2Me), 0.98 (3H, t, J = 7.3 Hz, Me), 1.10–2.02 (16H,
3
m, 8CH2), 2.64 (2H, t, J = 7.3 Hz, CH2), 3.72–3.92 (1H, m, CH), 4.75 (2H, s, SCH2), 4.86
(2H, s, NCH2), 5.79 (1H, d, 3J = 7.7 Hz, NH), 6.18 (1H, s, CH), 7.28 (1H, t, 3J = 7.1 Hz, CH),
7.41 (2H, t, 3J = 7.1 Hz, 2CH), 7.76 (2H, d, 3J = 7.1 Hz, 2CH), 8.31 (1H, br s, NH). 13C NMR:
δ = 13.6 (Me), 13.7 (2Me), 21.1 (CH2), 24.7 (CH2), 24.9 (2CH2), 25.4 (2CH2), 33.1 (2CH2),
33.9 (CH2), 39.1 (CH), 48.6 (CH2), 49.8 (CH2), 65.0 (C), 107.8 (C), 127.5 (C), 127.6 (2CH),
=
=
=
128.7 (CH), 129.2 (2CH), 137.7 (CH), 160.9 (C), 168.8 (C O), 168.9 (C O), 170.4 (C O).
EI-MS: m/z (%) = 512 (M+, 1.5), 483 (21), 211 (29), 125 (18), 97 (38), 91 (100), 57 (40), 29
(33). Anal. Calcd for C28H40N4O3S (512.71): C, 65.59; H, 7.86; N, 10.93; Found: C, 65.89; H,
8.08; N, 11.17%.
4.2.3. 2-(N-Benzyl-2-((6-oxo-4-propyl-1,6-dihydropyrimidin-2-yl)thio)acetamido)-N-
cyclohexyl-2-methyl propanamide (6c)
White powder, m.p. 98–100 ◦C; yield: 0.43 g (89%). IR (KBr): 3546, 3339, 1697, 1658,
1589 cm−1. 1H NMR: δ = 0.93 (3H, t, 3J = 7.2 Hz, Me), 1.00–1.95 (10H, m, 5CH2), 1.49 (6H,
s, 2Me), 1.54–1.63 (2H, m, CH2), 2.39 (2H, t, 3J = 7.2 Hz, CH2), 3.68–3.85 (1H, m, CH), 3.95
(2H, s, SCH2), 4.82 (2H, s, NCH2), 5.70 (1H, d, 3J = 7.7 Hz, NH), 5.99 (1H, s, CH), 7.31 (1H, t,
3J = 7.2 Hz, CH), 7.41 (2H, t, 3J = 7.2 Hz, 2CH), 7.53 (2H, d, 3J = 7.2 Hz, 2CH), 8.52 (1H, br s,
NH). 13C NMR: δ = 14.1 (Me), 21.4 (CH2), 24.8 (CH2), 25.4 (2Me), 25.9 (2CH2), 33.3 (2CH2),
34.6 (CH2), 39.9 (CH), 48.5 (CH2), 49.0 (NCH2), 63.6 (C), 108.5 (C), 126.4 (2CH), 127.5 (C),
=
=
=
127.9 (CH), 129.5 (2CH), 138.3 (CH), 160.3 (CH), 168.9 (C O), 169.6 (C O), 173.9 (C O).
EI-MS: m/z (%) = 484 (M+, 1.5), 211 (30), 169 (21), 125 (24), 97 (39), 91 (100), 57 (45), 43
(18). Anal. Calcd for C26H36N4O3S (484.65): C, 64.43; H, 7.49; N, 11.56; Found: C, 64.86; H,
7.58; N, 11.07%.
4.2.4. N-Cyclohexyl-1-(N-isopropyl-2-((6-oxo-4-propyl-1,6-dihydropyrimidin-2-
yl)thio)acetamido)cyclohexanecarboxamide (6d)
White powder, m.p. 93–96 ◦C; yield: 0.29 g (62%). IR (KBr): 3416, 3150, 1712, 1702, 1659 cm−1
.
3
3
1H NMR: δ = 0.99 (3H, t, J = 7.3 Hz, Me), 0.87–1.80 (20H, m, 10CH2), 1.15 (6H, d, J =
3
6.5 Hz, 2Me), 1.67–1.75 (2H, m, CH2), 2.51 (2H, t, J = 7.3 Hz, CH2), 3.75 (2H, s, SCH2),
3.95–4.11 (2H, m, 2CH), 5.87 (1H, d, 3J = 8.0 Hz, NH), 6.11 (1H, s, CH), 7.45 (1H, br s, NH).
13C NMR: δ = 13.8 (Me), 19.8 (CH2), 20.0 (2CH2), 21.0 (2Me), 24.7 (CH2), 24.9 (2CH2), 26.5
(CH2), 27.6 (2CH2), 30.9 (CH2), 31.5 (2CH2), 33.8 (CH), 42.2 (CH), 47.7 (CH2), 54.5 (C), 108.8
=
=
=
(C), 155.0 (CH), 160.7 (C), 167.7 (C O), 169.3 (C O), 172.7 (C O). EI-MS: m/z (%) = 476
(M+, 4), 433 (15), 211 (100), 209 (21), 125 (28), 97 (36), 57 (41), 43 (52). Anal. Calcd for
C25H40N4O3S (476.68): C, 62.99; H, 8.46; N, 11.75; Found: C, 63.12; H, 8.78; N, 11.23%.
4.2.5. N-Cyclohexyl-1-(N-ethyl-2-((6-oxo-4-propyl-1,6-dihydropyrimidin-2-
yl)thio)acetamido)cyclopentane carboxamide (6e)
White powder, m.p. 96–98 ◦C; yield: 0.32 g (71%). IR (KBr): 3454, 3340, 1677, 1666, 1656 cm−1
.
3
3
1H NMR: δ = 0.98 (3H, t, J = 7.7 Hz, Me), 1.10–1.94 (20H, m, 10CH2), 1.32 (3H, t, J =
7.0 Hz, Me), 2.73 (2H, t, 3J = 7.7 Hz, CH2), 3.61 (2H, q, 3J = 7.0 Hz, CH2), 3.86–3.90 (1H, m,

324 A.S. Shahvelayati and Z. Esmaeeli
CH), 4.09 (2H, s, SCH2), 5.87 (1H, d, 3J = 7.5 Hz, NH), 6.16 (1H, s, CH), 7.76 (1H, br s, NH).
13C NMR: δ = 13.7 (Me), 16.3 (Me), 21.1 (CH2), 23.0 (2CH2), 24.7 (CH2), 25.4 (2CH2), 25.5
(2CH2), 32.6 (2CH2), 33.0 (CH2), 39.1 (CH2), 39.9 (C), 48.3 (CH2), 65.9 (C), 108.1 (C), 159.9
+
=
=
=
(CH), 160.5 (C), 170.4 (C O), 170.5 (C O), 172.5 (C O). EI-MS: m/z (%) = 448 (M , 2),
419 (19), 211 (100), 195 (16), 125 (28), 97 (41), 57 (37), 29 (24). Anal. Calcd for C23H36N4O3S
(448.62): C, 61.58; H, 8.09; N, 12.49; Found: C, 61.75; H, 8.78; N, 12.27%.
4.2.6. 1-(N-Benzyl-2-((6-oxo-4-propyl-1,6-dihydropyrimidin-2-yl)thio)acetamido)-N-
cyclohexylcyclohexanecarboxamide (6f)
White powder, m.p. 73–74 ◦C; yield: 0.44 g (85%). IR (KBr): 3285, 3064, 1686, 1667, 1590 cm−1
.
1H NMR: δ = 0.934 (3H, t, J = 7.0 Hz, Me), 1.38–1.88 (22H, m, 11CH2), 2.42 (2H, t, J =
7.0 Hz, CH2), 3.68–3.87 (1H, m, CH), 3.99 (2H, s, SCH2), 4.84 (2H, s, NCH2), 6.02 (1H, s, CH),
6.42 (1 H, d, 3J = 7.7 Hz, NH), 7.28 (1H, t, 3J = 7.5 Hz, CH), 7.30 (2H, t, 3J = 7.5 Hz, 2CH),
7.39 (2H, d, 3J = 7.5 Hz, 2CH), 8.31 (1H, br s, NH). 13C NMR: δ = 14.0 (Me), 21.5 (CH2), 23.4
(CH2), 25.2 (CH2), 25.7 (2CH2), 25.9 (2CH2), 30.1 (2CH2), 33.2 (2CH2), 33.3 (CH2), 39.1 (CH),
3
3
48.9 (CH2), 49.1 (CH2), 67.5 (C), 107.8 (C), 126.4 (2CH), 127.9 (C), 129.4 (2CH), 129.9 (CH),
+
=
=
=
148.4 (CH), 168.5 (C O), 169.0 (C), 170.5 (C O), 172.0 (C O). EI-MS: m/z (%) = 524 (M ,
1), 211 (20), 209 (12), 125 (18), 97 (43), 91 (100), 57 (42), 43 (24). Anal. Calcd for C29H40N4O3S
(524.72): C, 66.38; H, 7.68; N, 10.68; Found: C, 66.48; H, 7.88; N, 10.17%.
4.2.7. N-Cyclohexyl-2-ethyl-2-(N-ethyl-2-((6-oxo-4-propyl-1,6-dihydropyrimidin-2-
yl)thio)acetamido)butanamide (6g)
White powder, m.p. 81–84 ◦C; yield: 0.35 g (77%). IR (KBr): 3316, 3210, 1686, 1643, 1590 cm−1
.
1H NMR: δ = 0.84 (6H, t, 3J = 7.2 Hz, 2Me), 0.96 (3H, t, 3J = 7.6 Hz, Me), 1.05–2.10 (16H, m,
8CH2), 1.42 (3H, t, 3J = 7.1 Hz, Me), 2.44 (2H, t, 3J = 7.6 Hz, CH2), 3.55 (2H, q, 3J = 7.1 Hz,
NCH2), 3.74–3.81 (1H, m, CH), 4.09 (2H, s, SCH2), 5.68 (1H, d, 3J = 8.0 Hz, NH), 6.02 (1H,
s, CH), 7.79 (1H, br s, NH). 13C NMR: δ = 8.4 (2Me), 13.7 (Me), 17.2 (Me), 21.1 (CH2), 23.4
(CH2), 24.9 (2 CH2), 25.6 (2CH2), 32.9 (2CH2), 34.4 (CH2), 39.1 (CH2), 39.9 (C), 48.6 (CH2),
=
=
=
65.9 (C), 108.1 (C), 160.1 (CH), 164.2 (C), 170.4 (C O), 170.5 (C O), 172.3 (C O). EI-MS:
m/z (%) = 450 (M+, 3.5), 421 (32), 211 (100), 197 (18), 125 (21), 97 (28), 57 (40), 29 (26).
Anal. Calcd for C23H38N4O3S (450.6): C, 61.30; H, 8.50; N, 12.43; Found: C, 61.89; H, 8.78; N,
12.23%.
4.2.8. 2-(N-Benzyl-2-((6-oxo-4-propyl-1,6-dihydropyrimidin-2-yl)thio)acetamido)-N-
(tert-butyl)-2-methylpropanamide (6h)
White powder, m.p. 75–76 ◦C; yield: 0.41 g (90%). IR (KBr): 3417, 3031, 1689, 1660, 1610 cm−1
.
1H NMR: δ = 0.91 (3H, t, 3J = 7.3 Hz, Me), 1.32 (9H, s, CMe3), 1.46 (6H, s, 2Me), 1.53–1.61
(2H, m, CH2), 2.39 (2H, t, 3J = 7.3 Hz, CH2), 4.02 (2H, s, SCH2), 4.81 (2H, s, NCH2), 5.65 (1H,
s, NH), 5.99 (1H, s, CH), 7.29 (1H, t, 3J = 7.1 Hz, CH), 7.39 (2H, t, 3J = 7.1 Hz, 2CH), 7.46 (2H,
d, 3J = 7.1 Hz, 2CH), 8.01 (1H, br s, NH). 13C NMR: δ = 14.0 (Me), 21.4 (CH2), 24.9 (2Me),
28.9 (CMe3), 31.3 (CH2), 39.4 (C), 48.7 (CH2), 51.6 (NCH2), 64.1 (C), 108.1 (C), 126.4 (2CH),
=
=
127.6 (C), 127.9 (CH), 129.5 (2CH), 138.4 (CH), 165.3 (C), 168.4 (C O), 169.3 (C O), 173.9
+
=
(C O). EI-MS: m/z (%) = 458 (M , 1.6), 401 (18), 211 (27), 143 (23), 99 (22), 91 (100), 57
(61). Anal. Calcd for C24H34N4O3S (458.62): C, 62.85; H, 7.47; N, 12.22; Found: C, 63.15; H,
7.78; N, 12.36%.

Journal of Sulfur Chemistry 325
4.2.9. N-(tert-Butyl)-2-(N-ethyl-2-((6-oxo-4-propyl-1,6-dihydropyrimidin-2-
yl)thio)acetamido)-2-methylpropanamide (6i)
White powder, m.p. 79–81 ◦C; yield: 0.31 g (79%). IR (KBr): 3459, 3346, 1739, 1690, 1653 cm−1
.
1H NMR: δ = 0.94 (3H, t, J = 7.3 Hz, Me), 1.20 (9H, s, CMe3), 1.27 (3H, t, J = 7.2 Hz,
Me), 1.49 (6H, s, 2Me), 1.63–1.65 (2H, m, CH2), 2.41 (2H, t, 3J = 7.3 Hz, CH2), 3.58 (2H, q,
3J = 7.2 Hz, NCH2), 3.99 (2H, s, SCH2), 5.58 (1H, s, NH), 5.98 (1H, s, CH), 8.10 (1H, br s, NH).
13C NMR: δ = 14.2 (Me), 16.8 (Me), 21.1 (CH2), 24.6 (2Me), 28.6 (CMe3), 29.7 (CH2), 33.5
3
3
=
(CH2), 39.9 (C), 50.9 (CH2), 63.0 (C), 107.4 (C),+154.0 (CH), 169.2 (C), 170.4 (C O), 170.5
=
=
(C O), 173.8 (C O). EI-MS: m/z (%) = 396 (M , 4), 367 (21), 211 (100), 143 (17), 99 (28),
57 (75), 29 (10). Anal. Calcd for C19H32N4O3S (396.55): C, 57.55; H, 8.13; N, 14.13; Found: C,
57.50; H, 8.48; N, 13.96%.
4.2.10. 1-(N-Benzyl-2-((6-oxo-4-propyl-1,6-dihydropyrimidin-2-yl)thio)acetamido)-N-
cyclohexylcyclopentanecarboxamide (6j)
White powder, m.p. 87–88 ◦C; yield: 0.34 g (67%). IR (KBr): 3325, 3098, 1685, 1660, 1640 cm−1
3
3
1H NMR: δ = 0.91 (3H, t, J = 7.5 Hz, Me), 0.89–1.92 (20H, m, 10CH2), 2.39 (2H, t, J =
7.5 Hz, CH2), 3.65–3.70 (1H, m, CH), 3.96 (2H, s, SCH2), 4.83 (2H, s, NCH2), 5.68 (1H, d,
3J = 8.0 Hz, NH), 6.01 (1H, s, CH), 7.32 (1H, t, J = 7.2 Hz, CH), 7.41 (2H, t, J = 7.2 Hz,
3
3
2CH), 7.49 (2H, d, J = 7.2 Hz, 2CH), 7.82 (1H, br s, NH). 13C NMR: δ = 14.1 (Me), 21.1
3
(CH2), 22.7 (2CH2), 24.3 (CH2), 24.9 (2CH2), 25.5 (2CH2), 31.8 (2CH2), 32.8 (CH2), 39.4 (CH),
48.2 (CH2), 48.9 (CH2), 63.2 (C), 108.0 (C), 126.1 (2CH), 127.5 (C), 127.6 (CH), 129.1 (2CH),
+
=
=
=
135.3 (CH), 166.0 (C), 168.3 (C O), 169.3 (C O), 173.7 (C O). EI-MS: m/z (%) = 510 (M ,
1.7), 211 (29), 195 (18), 97 (21), 91 (100), 57 (33), 43 (13). Anal. Calcd for C28H38N4O3S
(510.69): C, 65.85; H, 7.50; N, 10.97; Found: C, 66.18; H, 7.68; N, 11.17%.
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