Synthesis of 5-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-4-amino- 1,2,4-triazole-3-thione and its reactions with polyfunctional electrophiles

Article abstract of DOI:10.1007/s007060170070

In the reaction of 5-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-1,3,4- oxadiazole-2-thione with hydrazine hydrate, 5-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-4- amino-1,2,4-triazole-3-thione was formed. The reactions of the latter with ethyl bromoacetate and chloroacetonitrile in the presence of triethylamine proceeded under formation of the corresponding S-alkylated derivatives, whereas from its reaction with ω-bromoacetophenone and ethyl 4-chloroacetoacetate triazolothiadiazines were obtained. Treatment of the title compound with ethyl 2-chloroacetoacetate led to the formation of 5-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-4-N- acetylamino-(3-ethoxy-carbonylmethylthio)-1,2,4-triazole. Performing of the latter reaction without basic catalyst gave a triazolothiadiazine. Treatment of the S-alkylated derivatives with sodium methoxide resulted in triazolothiadiazines via a cyclocondensation reaction.

Full text of DOI:10.1007/s007060170070

Monatshefte fuÈr Chemie 132, 825±831 (2001)
Synthesis of 5-(6-Methyl-2,4-dioxo-1,2,3,4-
tetrahydro-3-pyrimidinyl)-methyl-4-amino-
1,2,4-triazole-3-thione and its Reactions with
Polyfunctional Electrophiles
Ã
and Sigitas Tumkevicius
Povilas Vainilavicius , Romualdas Smicius, Virginija Jakubkiene,
Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, LT-2006 Vilnius,
Lithuania
Summary. In the reaction of 5-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-1,3,4-
oxadiazole-2-thione with hydrazine hydrate, 5-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidi-
nyl)-methyl-4-amino-1,2,4-triazole-3-thione was formed. The reactions of the latter with ethyl
bromoacetate and chloroacetonitrile in the presence of triethylamine proceeded under formation of
the corresponding S-alkylated derivatives, whereas from its reaction with !-bromoacetophenone and
ethyl 4-chloroacetoacetate triazolothiadiazines were obtained. Treatment of the title compound with
ethyl 2-chloroacetoacetate led to the formation of 5-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-
pyrimidinyl)-methyl-4-N-acetylamino-(3-ethoxy-carbonylmethylthio)-1,2,4-triazole. Performing of
the latter reaction without basic catalyst gave a triazolothiadiazine. Treatment of the S-alkylated
derivatives with sodium methoxide resulted in triazolothiadiazines via a cyclocondensation reaction.
Keywords. Alkylation; Cyclocondensation; Pyrimidine; 1,2,4-Triazole-3-thiones; 1,2,4-Triazolo[3,
4-b]-1,3,4-thiadiazines.
Introduction
N-Alkylated oxopyrimidines with functional groups in the alkyl fragment can be
considered to some extent as analogs of natural nucleosides. Therefore, these
compounds have acquired increasing importance as agents with anti-in¯ammatory
[1, 2], anticancer [3], blood platelet agregation inhibitory [4], immunotropic [2, 5],
and antivirus [6±9] activity. Nevertheless, the chemistry of oxopyrimidines bearing
nitrogen heterosystems in N-alkyl groups has been studied insuf®ciently. Recently,
we have reported on the synthesis of oxopyrimidine derivatives with a pyrazole
moiety in the N-alkyl group, which were found to be potential cardiotonic agents
[10]. In continuation of our interest in the synthesis of such compounds, we now
report on the synthesis of 5-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-
methyl-4-amino-1,2,4-triazol-3-thione and its reactions with various electrophilic
Ã
Corresponding author

826
P. Vainilavicius et al.
reagents. The choice of the title compound was based on two reasons. Firstly, such
heterosystems are polyfunctional compounds, and both moieties ± pyrimidine and
azole ± can take part in reactions with electrophilic and nucleophilic reagents. Thus,
the study of their properties is of considerable interest in view of their chemistry.
Secondly, derivatives of such biheterocycles can possess valuable pharmacological
properties, because their structures include both a pyrimidine nucleus and a 4-amino-
1,2,4-triazole moiety, which is present in biologically active compounds [11, 12].
Results and Discussion
The synthesis of 5-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-
4-amino-1,2,4-triazol-3-thione (4) is outlined in Scheme 1.
Ester 1 was obtained by regioselective alkylation of 4-methyluracil with ethyl
bromoacetate according to Ref. [13]. Treatment of 1 with an excess of 100%
hydrazine hydrate afforded hydrazide 2. Oxadiazole 3 was obtained according to
Ref. [14] by the reaction of 2 with carbon disul®de in the presence of potassium
hydroxide. It is known that 5-substituted 1,3,4-oxadiazol-2-thiones undergo
recyclization with the formation of 4-amino-1,2,4-triazole-3-thiones in the reaction
with hydrazine hydrate [15]. In order to elaborate an ef®cient method for the
synthesis of 4, the reaction of 3 with hydrazine hydrate was studied using different
solvents (water, ethanol, and dioxane (method A)). The best yield (55%) was
obtained when the reaction was carried out in ethanol. Compound 4 was also
synthesized in 40% yield by the reaction of 1 with thiocarbohydrazide in the
presence of sodium methoxide (method B).
All alkylation reactions of 4 with electrophilic reagents were carried out under
similar conditions using ethanol as a solvent and triethylamine as a base. The
alkylation of 4 with ethyl bromoacetate and chloroacetonitrile gave the S-alkylated
Scheme 1

Reactions of a Pyrimidinyl-Substituted Triazolethione
827
Scheme 2
derivatives 5 and 6. In the reaction of 4 with !-bromoacetophenone and 4-chloro-
acetoacetate, intramolecular cyclocondensation of the S-alkylated products took
place to give the triazolothiadiazines 7 and 8 (Scheme 2).
The unexpected 4-acetylamino-3-ethoxycarbonylmethylthio derivative 11 was
obtained in an analogous reaction of 4 with ethyl 2-chloroacetoacetate (method A).
Probably, the reaction proceeded via the formation of the intermediate 11a, which
underwent a cleavage similar to that of ꢀ-oxocarboxylic acids under basic con-
ditions (triethylamine). The course of the reaction was proven by the formation of
the corresponding triazolothiadiazine 13 when the reaction between 4 and ethyl
2-chloroacetoacetate was carried out without triethylamine. Moreover, 11 was also
obtained by an alternative synthesis, including acetylation of 4 with acetic
anhydride and following alkylation of the obtained 4-acetylamino-1,2,4-triazole-2-
thione 12 with ethyl bromoacetate (method B). Upon treatment with sodium
methoxide in methanol, the S-alkyl derivatives 5 and 6 underwent a cyclocondensa-
tion reaction to give triazolothiadiazines 9 and 10.
In the IR spectra of compounds 1±13, absorption bands characteristic for uracil
1
derivatives [16, 17] were found in the regions of 1665±1640 and 1723±1691 cm .

828
P. Vainilavicius et al.
The IR spectra of compounds 1, 5, 8, 9, and 12 are characterized by the absorption
1
of the ester C=O and C±O±C groups at 1735±1720 and 1229±1175 cm . In the
1
spectrum of 6, the absorption of the CN group was observed at 2248 cm . The IR
spectra of 2, 9, 11, and 12 are characterized by the absorption of amide groups in the
1
regions of 1732±1723 (C=O) and 3100±3059 (NH) cm . The IR spectra of
oxadiazolethione 3 and aminotriazolethione 4 (absorption of N±C=S at 1507 and
1
1458 cm , respectively) indicate that these compounds exist in the thione form.
The C±O±C absorption band of oxadiazole 3 is observed in the region characteristic
1
for oxadiazoles (1063 cm [18]).
In the 1H NMR spectra of all compounds the signals of the pyrimidine ring and
its substituents can be observed: 2.06±2.11 (CH3), 4.29±5.23 (5-CH), and 9.1±11.35
(NH) ppm. The protons of SCH2 group of 5±11 resonate at 3.71±4.44 ppm, whereas
the signal of SCH group of 13 is observed at 5.24 ppm. The signal of the NH2 group
of 4-aminotriazoles 4±6 is observed at 5.69±6.14 ppm as a broad singlet, whereas
the signal of the amino group of 10 is shifted down®eld to 7.16 ppm. These data
together with the results of elemental analyses con®rm the structures of the
synthesized compounds.
Experimental
Melting points were determined in open capillaries and are uncorrected. IR spectra were measured in
Nujol mulls on a Perkin-Elmer FT spectrophotometer Spectrum BX II. 1H NMR spectra were
recorded with a Tesla BS 570 A spectrometer (80 MHz) using TMS as internal standard. The
experimental values of the microanalyses for compounds 1±13 agreed with the calculated ones.
Ethyl (6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-acetate (1; C9H12N2O4)
1 was synthesized in analogy to the procedure for the corresponding methyl ester as described in
Ref. [13].
Yield: 68%; m.p.: 144±145ꢀC (ethyl acetate); IR: ꢁ ˆ 3108 (NH), 1735, 1712, 1660 (CO), 1228
1
(C±O±C) cm 1; H NMR (DMSO-d6): ꢂ ˆ 1:15 (t, J ˆ 7 Hz, 3H, CH3), 2.03 (s, 3H, CH3), 4.07
(q, J ˆ 7 Hz, 2H, OCH2), 4.41 (s, 2H, NCH2), 5.45 (s, 1H, CH), 7.29 (s, 1H, NH) ppm.
Hydrazide of (6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-acetic acid (2; C7H10N4O3)
To a suspension of 1 (16 g, 0.075 mol) in 60 cm3 MeOH, 10 cm3 100% hydrazine hydrate (11.3 g,
0.23 mol) were added under stirring. The reaction mixture was stirred at room temperature for 8 h and
then left at 0ꢀC for additional 8 h. The precipitate was ®ltered off, washed with 2-propanol, and
recrystallized.
Yield: 10.9 g (74%); m.p.: 259±261ꢀC (H2O); IR: ꢁ ˆ 3072 (NH), 1732, 1703, 1665 (CO), 1614
1
(NH2), 1529, 1284 (C±N), 1102 (NH2), 1101 (N±N) cm 1; H NMR (DMSO-d6): ꢂ ˆ 2:08 (s, 3H,
CH3), 4.29 (m, 4H, NCH2, NH2), 5.46 (s, 1H, CH), 9.10 (s, 1H, NH), 11.16 (s, 1H, NH) ppm.
5-(6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-1,3,4-oxadiazole-3-thione
(3; C8H8N4O3S)
To a solution of KOH (5.94 g, 0.106 mol) in 150 cm3 EtOH, 6.37cm3 CS2 (8.06 g, 0.106 mol) were
added, and the reaction mixture was stirred at room temperature for 15 min. Then, hydrazide 2 (20 g,
0.101 mol) and 150 cm3 EtOH were added, and the reaction mixture was re¯uxed for 16 h and
subsequently evaporated to dryness. The residue was dissolved in 300 cm3 H2O, and the solution was

Reactions of a Pyrimidinyl-Substituted Triazolethione
829
treated with conc. HCl to reach pH ꢁ 3. The solid was ®ltered off, washed with water, and
recrystallized.
Yield: 17.7 g (73%); m.p.: 246±247ꢀC (H2O); IR: ꢁ ˆ 3101 (NH), 1723, 1651 (CO), 1507 (CS),
1063 (C±O±C) cm 1; 1H NMR (DMSO-d6): ꢂ ˆ 2:10 (s, 3H, CH3), 5.03 (s, 2H, NCH2), 5.56 (s, 1H,
CH), 11.49 (s, 1H, NH) ppm.
5-(6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-4-amino-1,2,4-triazole-3-thione
(4; C8H10N6O2S)
Method A. To a suspension of 3 (2 g, 8.33 mmol) in 40 cm3 H2O, 0.61 cm3 100% hydrazine hydrate
(0.63 g, 12.5mmol) were added, and the reaction mixture was re¯uxed for 4 h. Then, KOH (0.7 g,
12.5 mmol) was added, insoluble material was ®ltered off, and the ®ltrate was acidi®ed with conc.
HCl to pH ꢁ 3. The solid was ®ltered off, washed with water, and recrystallized.
Yield: 0.51 g (24%); m.p.: 285±287ꢀC (H2O); IR: ꢁ ˆ 3099 (NH2), 3046 (NH), 1716, 1639 (CO),
1605 (NH2), 1498 (CS) cm 1; 1H NMR (DMSO-d6): ꢂ ˆ 2:10 (s, 3H, CH3), 4.99 (s, 2H, NCH2), 5.57
(s, 1H, CH), 5.69 (s, 2H, NH2), 11.33 (s, 1H, NH), 13.56 (s, 1H, NH) ppm.
When EtOH was used as a solvent, the reaction time was 7 h (yield: 1.16 g, 55%); in the case of
dioxane, the reaction required 4.5 h to complete (yield: 0.8 g, 38%).
Method B. To a solution of sodium methoxide (1.89 g, 35 mmol) in 50 cm3 MeOH, 1.59 g thio-
carbohydrazide (15 mmol) were added, and the mixture was re¯uxed for 5 min. 2.12 g 1 (10 mmol)
were added, and the reaction mixture was re¯uxed under stirring for 14 h and subsequently evaporated
to dryness. The residue was dissolved in 40 cm3 H2O, ®ltered, and the ®ltrate was acidi®ed with conc.
HCl to pH ꢁ 3. The precipitate was ®ltered off, washed with water, and recrystallized. Yield: 1.02 g
(40%).
5-(6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-4-amino-3-
(ethoxycarbonylmethylthio)-1,2,4-triazole (5; C12H16N6O4S)
A mixture of 4 (1 g, 3.94 mmol), 30 cm3 EtOH, 0.55 cm3 triethylamine (0.4 g, 3.94 mmol), and
0.44 cm3 ethyl bromoacetate (0.66 g, 3.94 mmol) was re¯uxed for 6 h, then evaporated to half its
initial volume, and cooled. The precipitate was ®ltered off, washed with a small amount of cold water,
and recrystallized.
Yield: 0.99 g (75%); m.p.: 149±151ꢀC (EtOH); IR: ꢁ ˆ 3290 (NH2), 3172 (NH), 1720, 1691, 1641
1
(CO), 1621 (NH2), 1226 (C±O±C) cm 1; H NMR (DMSO-d6): ꢂ ˆ 1:21 (t, J ˆ 7 Hz, 3H, CH3),
2.11 (s, 3H, CH3), 4.04 (s, 2H, SCH2), 4.14 (q, J ˆ 7 Hz, 2H, OCH2), 5.07 (s, 2H, NCH2), 5.56 (s,
1H, CH), 6.11 (s, 2H, NH2), 11.30 (s, 1H, NH) ppm.
5-(6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-4-amino-3-(cyanomethylthio)-
1,2,4-triazole (6; C10H11N7O2S)
A mixture of 4 (1 g, 3.94 mmol), 30 cm3 EtOH, 0.55 cm3 triethylamine (0.4 g, 3.94 mmol), and
0.25 cm3 chloroacetonitrile (0.3g, 3.94 mmol) was re¯uxed for 9 h and cooled. The precipitate was
®ltered off, washed with a small amount of cold water, and recrystallized.
Yield: 0.63 g (54%); m.p.: 205±207ꢀC (EtOH); IR: ꢁ ˆ 3266 (NH2), 2248 (CN), 1711, 1653 (CO),
1
1627 (NH2) cm 1; H NMR (DMSO-d6): ꢂ ˆ 2:10 (s, 3H, CH3), 4.27 (s, 2H, SCH2), 5.09 (s, 2H,
NCH2), 5.56 (s, 1H, CH), 6.14 (s, 2H, NH2), 11.24 (s, 1H, NH) ppm.
3-(6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-6-phenyl-7H-1,2,4-
triazolo[3,4-b]-1,3,4-thiadiazine (7; C16H14N6O2S)
Compound 7 was synthesized from 4 and !-bromoacetophenone according to the procedure described
for 5 (reaction time: 12 h).

830
P. Vainilavicius et al.
1
Yield: 0.84 g (60%); m.p.: 238±239ꢀC (EtOH); IR: ꢁ ˆ 3170 (NH), 1722, 1646 (CO) cm
;
1H NMR (DMSO-d6): ꢂ ˆ 2:10 (s, 3H, CH3), 4.44 (s, 2H, SCH2), 5.23 (s, 2H, NCH2), 5.58 (s, 1H,
CH), 7.63±8.00 (m, 5H, C6H5), 11.35 (s, 1H, NH) ppm.
3-(6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-6-(ethoxycarbonylmethyl)-
7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine (8; C14H16N6O4S)
Compound 8 was synthesized from 4 and ethyl 4-chloroacetoacetate according to the procedure
described for 5 (reaction time: 12 h).
Yield: 0.92 g (64%); m.p.: 203±205ꢀC (H2O); IR: ꢁ ˆ 3075 (NH), 1732, 1700, 1651 (CO), 1206
1
(C±O±C) cm 1; H NMR (DMSO-d6): ꢂ ˆ 1:24 (t, J ˆ 7 Hz, 3H, CH3), 2.10 (s, 3H, CH3), 3.81
(s, 2H, SCH2), 3.97 (s, 2H, CH2), 4.18 (q, J ˆ 7 Hz, 2H, OCH2), 5.09 (s, 2H, NCH2), 5.56 (s, 1H,
CH), 11.32 (s, 1H, NH) ppm.
3-(6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-1,2,4-triazolo[3,4-b]-1,3,4-
thiadiazin-6-one (9; C10H10N6O3S)
To a suspension of 5 (1 g, 2.94 mmol) in 40 cm3 MeOH, 2.94 cm3 1 M methanolic sodium methoxide
(2.94 mmol) were added. The reaction mixture was re¯uxed under stirring for 10 h and evaporated to
dryness. The residue was dissolved in 20 cm3 H2O and acidi®ed with 1 M HCl to pH ꢁ 3 under
cooling. The precipitate was ®ltered off, washed with water, and recrystallized.
Yield: 0.64 g (74%); m.p.: >300ꢀC (aqueous DMF); IR: ꢁ ˆ 3104 (NH), 1732, 1700, 1640 (CO)
cm 1; 1H NMR (DMSO-d6): ꢂ ˆ 2:11 (s, 3H, CH3), 3.85 (s, 2H, SCH2), 5.07 (s, 2H, NCH2), 5.57 (s,
1H, CH), 11.32 (s, 1H, NH) ppm.
3-(6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-7H-1,2,4-triazolo[3,4-b]-
1,3,4-thiadiazin-6-ylamine (10; C10H11N7O2S)
To a hot solution of 6 (1 g, 3.58 mmol) in 40 cm3 MeOH, 0.36cm3 0.5 M methanolic sodium
methoxide (0.18 mmol) were added, and the reaction mixture was stirred at 50ꢀC for 72 h. The
precipitate was ®ltered off, washed with hot MeOH, and recrystallized.
Yield: 0.36 g (36%); m.p.: >300ꢀC (aqueous DMF); IR: ꢁ ˆ 3186 (NH2), 3082 (NH), 1716, 1662
1
(CO), 1594 (NH2) cm 1; H NMR (DMSO-d6): ꢂ ˆ 2:10 (s, 3H, CH3), 3.71 (s, 2H, SCH2), 4.97
(s, 2H, NCH2), 5.53 (s, 1H, CH), 7.16 (s, 2H, NH2), 10.92 (s, 1H, NH) ppm.
5-(6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-4-N-acetylamino-3-
(ethoxycarbonylmethylthio)-1,2,4-triazole (11; C14H18N6O5S)
Method A. A mixture of 4 (1 g, 3.94 mmol), 30 cm3 MeOH, 0.55 cm3 triethylamine (0.4 g, 3.94 mmol),
and 0.54 cm3 ethyl 2-chloroacetoacetate (0.65 g, 3.94mmol) was re¯uxed for 14 h, subsequently
evaporated to dryness, and the residue was recrystallized. Yield: 0.82 g (55%); m.p.: 188±190ꢀC
(H2O).
Method B. To a solution of 12 (1 g, 3.37 mmol) and 0.47 cm3 triethylamine (0.34 g, 3.37 mmol) in
20 cm3 EtOH, 0.37 cm3 ethyl bromoacetate (0.56 g, 3.37 mmol) were added. The reaction mixture was
re¯uxed for 3 h, evaporated to dryness, and the residue was recrystallized.
Yield: 0.67 g (52%); m.p.: 188±190ꢀC (H2O); IR: ꢁ ˆ 3098 (NH), 1723, 1700, 1645 (CO), 1187
1
(C±O±C) cm 1; H NMR (DMSO-d6): ꢂ ˆ 1:20 (t, J ˆ 7 Hz, 3H, CH3), 2.06 (s, 6H, 2CH3), 4.03
(s, 2H, SCH2), 4.12 (q, J ˆ 7 Hz, 2H, OCH2), 4.89 (s, 2H, NCH2), 5.54 (s, 1H, CH), 11.30 (s, 1H,
NH), 11.54 (s, 1H, NH) ppm.

Reactions of a Pyrimidinyl-Substituted Triazolethione
831
5-(6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-4-N-acetylamino-1,2,4-triazole-
3-thione (12; C10H12N6O3S)
To a suspension of 4 (1 g, 3.94 mmol) in 50 cm3 CH3COOH (conc.), 0.49 cm3 acetic anhydride
(0.53 g, 5.23 mmol) were added portionwise. The reaction mixture was re¯uxed for 8 h, evaporated to
dryness, and the residue was recrystallized.
Yield: 0.67 g (57%); m.p.: 299±301ꢀC (H2O); IR: ꢁ ˆ 1724, 1704, 1644 (CO), 1501 (CS) cm
1
;
1H NMR (DMSO-d6): ꢂ ˆ 2:08 (s, 6H, 2CH3), 4.80 (s, 2H, NCH2), 5.55 (s, 1H, CH), 11.27 (s, 2H,
2NH), 13.73 (s, 1H, NH) ppm.
3-(6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-7-(ethoxycarbonyl)-6-methyl-7H-
1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine (13; C14H16N6O4S)
A mixture of 4 (1 g, 3.94 mmol), 30 cm3 EtOH, and 0.54 cm3 ethyl 2-chloroacetoacetate (0.65 g,
3.94 mmol) was stirred at 60ꢀC for 18 h, cooled to room temperature, and neutralized with triethyl-
amine. The precipitate was ®ltered off, washed with a small amount of cold water, and recrystallized.
Yield: 0.64 g (45%); m.p.: 205±206.5ꢀC (H2O); IR: ꢁ ˆ 1727, 1700, 1655 (CO), 1175 (C±O±C)
cm 1; 1H NMR (DMSO-d6): ꢂ ˆ 1:14 (t, J ˆ 7 Hz, 3H, CH3), 2.08 (s, 3H, CH3), 2.41 (s, 3H, CH3),
4.12 (q, J ˆ 7 Hz, 2H, OCH2), 5.10 (s, 2H, NCH2), 5.24 (s, 1H, SCH), 5.55 (s, 1H, CH), 11.30 (s, 1H,
NH) ppm.
References
[1] Hardtmann GE, Ott H (1972) US Pat. 3663698; (1972) CA 77: 52313
[2] Krivonogov VP, Tolstikov GA, Murinov YI, Zarudy FS, Lazareva DN, Davidova VA, Ismagilova
AF, Spirikhin LV, Abrachmanov IB (1997) Khim Pharm Zh 31(7): 24
[3] Ozaki Sh, Watanabe Y, Hoshiko T, Mizuno H, Ishikawa K, Mori H (1984) Chem Pharm Bull 32:
733
[4] Meanwell NA (1991) US Pat. 4983610; (1991) CA 114: 164276
[5] Krivonogov VP, Tolstikov GA, Murinov YI, Zarudy FS, Lazareva DN, Ismagilova AF, Volkova
SS, Sakhautdinova GM, Afzaletdinova NG, Khisamutdinov RA, Spirikhin LV, Krivonogova II
(1993) Khim Pharm Zh 27(11): 41
[6] Tanaka H, Baba M, Hayakawa H, Sakamaki T, Miyasaka T, Ubasawa M, Takashima H, Sekiya K,
Nitta I, Shigeta S, Walker RT, Balzarini J, De Clercq E (1991) J Med Chem 34: 349
[7] Tanaka H, Takashima H, Ubasawa M, Sekiya K, Inoye N, Baba M, Shigeta S, Walker RT,
De Clercq E, Miyasaka T (1995) J Med Chem 38: 2860
[8] Danel K, Larsen E, Pedersen EB, Vestergaard BF, Nielsen C (1996) J Med Chem 39: 2427
[9] Pontikis R, Benhida R, Aubertin A-M, Grierson DG, Monneret C (1997) J Med Chem 40: 1845
[10] Sedereviciute V, Garaliene V, Vainilavicius P, Hetzheim A (1998) Pharmazie 53: 233
[11] Bhalerao UT, Muralikrishna Ch, Rani BR (1994) Tetrahedron 50: 4019
[12] Kalluraya B, Sreenivasa G, Holla BS (1993) Indian J Heterocycl Chem 3: 97; (1994) CA 121:
35476
[13] Vainilavicius P, Sedereviciute V, Mociskyte G (1992) Khim Geterotsikl Soedin 1665
[14] Ainsworth C (1956) J Am Chem Soc 78: 4475
[15] Reid JR, Heindel ND (1976) J Heterocycl Chem 13: 925
[16] Angell CL (1961) J Chem Soc 504
[17] Wittenburg E (1966) Chem Ber 99: 2380
[18] Charistos DA, Vagenas GV, Tzavellas LC, Tsoleridis CA, Rodios NA (1994) J Heterocycl Chem
31: 1593
Received November 20, 2000. Accepted January 15, 2001