Syntheses of some new azolopyrido-[4′,3′:4,5]thieno[2,3-d]pyrimidines

Article abstract of DOI:10.1002/hc.10030

Diethyl2-[(ethoxythioxomethyl)amino]4,5,6,7-tetrahydrothieno[2,3-c]-pyridin e-3,6-dicarboxylate 2, prepared from diethyl 2-isothiocyanato-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3,6-dicarboxylate 1 by boiling in anhydrous ethanol, was converted into pyrido[4′,3′:4,5]thieno[2,3-d]pyrimidine derivatives 3, 4 by treatment with hydrazine hydrate. The tetracyclic systems imidazo[1,2-a]pyrido-[4′,3′:4,5]-thieno[2,3-d]pyrimidine 9 and pyrido[4′,3′:4,5]-thieno[2,3-d][1,3]thiazolo-[3,2-a]pyrimidine 10 were synthesized by the reaction of 2 with 1,2-diaminoethane and aminoethanethiol, respectively. The hydrazino derivative 4 underwent cyclization reactions with orthoesters and nitrous acid to give the corresponding pyrido[4′,3′:4,5]thieno[2,3-d][1,2,4]triazolo[1,5-a]pyrimidines 5, 6 and pyrido[4′,3′:4,5]thieno[3,2-e][1,2,3,4]tetrazolo[1,5-a]pyrimidine 8, respectively. Moreover, reactions of 3 with cyanogen bromide, N-carbethoxyhydrazine, carbon disulfide, and ethyl chloroformate resulted in the formation of the new pyrido[4′,3′:4,5]thieno[2,3-d][1,3,4]thiadiazolo-[3,2-a]pyrimidine derivatives 12-15.

Full text of DOI:10.1002/hc.10030

Heteroatom Chemistry
Volume 13, Number 3, 2002
S0ynt0heses of Some New Azolopyrido-
[4 ,3 :4,5]thieno[2,3-d ]pyrimidines
Essam Kh. Ahmed
Chemistry Department, Faculty of Science, El-Minia University, El-Minia 61519, Egypt
Received 1 May 2001; revised 2 October 2001
have been reported to possess broad-spectrum an-
ABSTRACT:Diethyl2-[(ethoxythioxomethyl)amino]-
thelmintic activity [2]. Although there are many
4,5,6,7-tetrahydrothieno[2,3-c]-pyridine-3,6-dicarbo-
methods reported in the literature for the prepa-
xylate 2, prepared from diethyl 2-isothiocyanato-4,5,
ration of isothiocyanates [3], heterocyclic isothio-
6,7-tetrahydrothieno[2,3-c]pyridine-3,6-dicarboxylate
cyanates with an ester group at the ortho position
1 by boiling in anhydrous ethanol, was converted
have been only recently reported [4–11]. This
into pyrido[40,30:4,5]thieno[2,3-d]pyrimidine deriva-
prompted us to investigate the utility of heterocyclic
tives 3, 4 by treatment with hydrazine hydrate. The
isothiocyanates with an ester group at the ortho
tetracyclic systems imidazo[1,2-a]pyrido-[40,30:4,5]-
position. We have shown that these compounds
thieno[2,3-d]pyrimidine
9
and pyrido[40,30:4,5]-
are versatile starting materials for the syntheses
of heterocyclic thiourea derivatives, and different
fused heterocyclic systems [12,13]. In our ongo-
ing search for new heterocycles containing the
thienopyrimidine ring systems [14–17], the present
paper follows this line of research by reporting on
a new, rapid, and convenient synthesis of diethyl 2-
[(ethoxythioxomethyl)amino]-4,5,6,7-tetrahydrothi-
eno[2,3-c]pyridine-3,6-dicarboxylate 2 and its utility
in the synthesis of not yet reported pyrido[40,30:4,5]-
thieno[2,3-d]pyrimidines 3, 4, pyrido[40,30:4,5]thie-
no[2,3-d][1,2,4]triazolo[1,5-a]-pyrimidines 5, 6 and
pyrido[40,30:4,5]thieno[2,3-d][1,3,4]thiadiazolo[3,2-
a]pyrimidines 12–15.
thieno[2,3-d][1,3]thiazolo-[3,2-a]pyrimidine 10 were
synthesized by the reaction of 2 with 1,2-diamino-
ethane and aminoethanethiol, respectively. The hydra-
zino derivative 4 underwent cyclization reactions with
orthoesters and nitrous acid to give the correspon-
ding pyrido[40,30:4,5]thieno[2,3-d][1,2,4]triazolo[1,5-
a]pyrimidines 5, 6 and pyrido[40,30:4,5]thieno[3,2-e]-
[1,2,3,4]tetrazolo[1,5-a]pyrimidine 8, respectively.
Moreover, reactions of 3 with cyanogen bromide,
N-carbethoxyhydrazine, carbon disulfide, and ethyl
chloroformate resulted in the formation of the
new pyrido[40,30:4,5]thieno[2,3-d][1,3,4]thiadiazolo-
C
[3,2-a]pyrimidine derivatives 12–15.
2002 Wiley
Periodicals, Inc. Heteroatom Chem 13:280–286, 2002;
Published online in Wiley Interscience (www.interscience.
wiley.com). DOI 10.1002/hc.10030
RESULTS AND DISCUSSION
It has been found that refluxing diethyl 2-isothio-
cyanato-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3,
6-dicarboxylate 1 [12] with anhydrous ethanol for
20 h resulted in the formation of diethyl 2-[(etho-
xythioxomethyl) amino]-4,5,6,7- tetrahydrothieno-
[2,3-c]pyridine-3,6-dicarboxylate 2. Compound 2,
with two reactive groups at ortho positions, was
converted into ethyl 3-amino-4-oxo-2-thioxo-1,3,
4,5,6,8-hexahydropyrido[40,30:4,5]thieno[2,3-d ]pyri-
INTRODUCTION
The antiparasitic properties exhibited by a variety
of isothiocyanates have been very well documented
[1]. Furthermore, various substituted thioureas also
Correspondence to: Essam Kh. Ahmed; e-mail: essamkhalaf24@
hotmail.com.
c
2002 Wiley Periodicals, Inc.
midine-7(2H)-carboxylate
3
by the action of
280

Syntheses of Some New Azolopyrido[40,30:4,5]thieno[2,3-d]pyrimidines 281
hydrazine hydrate at room temperature, while, by
structure assigned. The IR spectrum showed two
broad bands in the region 3200–3400 cm 1 character-
istic of the NH2 group. The 2-amino group protons
resonate further downfield, at = 7.99 than the
3-amino group protons of the precursor 3. Conden-
sation of 3 with N-carbethoxyhydrazine in the pre-
sence of hydrochloric acid afforded ethyl 2-hydra-
zino-10-oxo-8, 9-dihydro-10H-pyrido[40,30:4,5]thieno-
[2,3-d][1,3,4]-thiadiazolo[3,2-a]pyrimidine-7(6H)-
carboxylate 13, which in its IR spectrum showed
heating, the replacement of the mercapto group by
the hydrazino group took place to give the hydrazino
derivative 4.
Compound 4 was also obtained by treatment of
3 with hydrazine hydrate in ethanol at reflux tem-
perature. Compound 4 could be further cyclized into
tetracyclic azolopyrido[40,30:4,5]thieno[2,3-d]pyrim-
idine derivatives. For example, when 4 was refluxed
with triethyl orthoformate, only one product was ob-
tained, and this was identified as the new heterocycle
ethyl 3-amino-10-oxo-3,8,9,10-tetrahydropyrido[40,
30:4,5]thieno[2,3-d][1,2,4]triazolo[1,5a]pyrimidine-
7-(6H)-carboxylate 5. The structure assignment of
compound 5 was obtained by elemental analyses, IR
1
absorption bands at 3240, 3205, and 3160 cm due
to NH and NH2 groups. It also showed another band
at 1670 due to the cyclic amide mooiety ( CO N).
Refluxing of compound 3 with carbon disulfide
in pyridine afforded ethyl 2-thioxo-10-oxo-6,7,8,9-
tetrahydropyrido[40,30 :4,5]thieno[2,3-d][1,3,4]thia-
diazolo[3,2-a]pyrimidine-7-carboxylate 14. The stru-
cture of 14 has been confirmed on the basis of IR
1
1
and H NMR spectroscopy. The H NMR spectrum
showed a two hydrogen proton singlet at = 6.20,
which was assigned to the NH2 group. This band
disappeared after D2O exchange. Other analytical
and spectroscopic data are given in the experimental
section. In the same manner, when compound 4 was
refluxed with triethyl orthoacetate, it gave ethyl 3-
amino-2-methyl-10-oxo-3,8,9,10-tetrahydro[40,30:4,
5]thieno[2,3-d][1,2,4]triazolo[1,5-a]pyrimidine-7-
(6H)-carboxylate 6. Treatment of compound 4 with
nitrous acid in a molar ratio of 1:1 gave ethyl 4-ami-
no-5-oxo-4,5,6,9-tetrahydropyrido[40,30:4,5]thieno-
[3,2-e][1,2,3,4]tetrazolo[1,5-a]pyrimidine-8(7H)-
carboxylate 8 through the intermediate formation
of the 2-azido derivative 7. The proof for this latter
1
and H NMR studies. The IR spectrum showed a
1
band at 3200–3180 cm for the NH group, and
NMR spectra showed a singlet at = 5.30 (1H, NH)
and this showed that compound 14 exists preferably
in the thione rather than in the thiol form. Another
new thiadiazolo derivative 15 was synthesized from
3 by reaction with ethyl chloroformate.
EXPERIMENTAL
Melting points were determined on a Gallenkamp
apparatus and are uncorrected. Elemental analyses
were performed at the microanalytical Laboratory,
1
reaction is the signal in the H NMR spectrum at
= 5.87 for the amino group, and its IR spectrum
showed no azide band. This compound exists only
in the tetrazolo form.
1
Cairo University. 13C and H NMR spectra: Bruker
AC 200 (1H: 200.13 MHz, 13C: 50.32 MHz), 5 mm
dual 1H/13C-VT probe at 300 K; solvent: DMSO-d6 and
CDCl3, respectively, values are given relative to the
internal standard TMS ( = 0 ppm). IR spectra were
recorded on a Shimadzu 470 Spectrophotometer in
KBr pellets. Mass spectra were recorded on a Finni-
gan MAT 95-A spectrometer.
When the thiourethane 2 reacted with 1,2-diami-
noethane, it gave ethyl 5-oxo-1,2,3, 6,7,9-hexahydro-
imidazo[1,2-a]pyrido[40,30:4,5]thieno[2,3-d]pyrimi-
din-8(5H)-carboxylate 9. In this case, the cyclization
took place only to the nitrogen at position 3 in the
pyrimidine system. Similarly, ethyl 5-oxo-2,3,6,9-tet-
rahydro-5H-pyrido[40,30:4,5]thieno[2,3-d][1,3]thia-
zolo[3,2-a]pyrimidine-8(7H)-carboxylate 10 was ob-
tained from the reaction of 2 with aminoethanethiol
hydrochloride in pyridine (Scheme 1).
As illustrated in Scheme 2, compound 3 was
proved to be a versatile starting material for the synt-
hesis of the new pyrido[40,30:4,5]thieno[2,3-d][1,3,
4]thiadiazolo-[3,2-a]pyrimidine derivatives 12–15.
Upon treatment of 3 with cyanogen bromide, the
thiadiazolo compound, namely ethyl 2-amino-10-
oxo-8,9-dihydro-10H-pyrido[40,30:4,5]thieno[2,3-d]-
[1,3,4]thiadiazolo[3,2-a]pyrimidine-7(6H)-carboxy-
late 12, was obtained. This reaction proceeded via
the thiocyanate 11 as an intermediate. The analyt-
ical and spectral data are in accordance with the
Diethyl 2-[(ethoxythioxomethyl)amino]-4,5,6,7-
tetrahydrothieno[2,3-c]pyridine-3,6-dicarboxy-
late (2)
A solution of 1 (0.41 g, 0.0012 mol) in anhydrous
ethanol (30 ml) was heated under reflux for 20 h.
The solvent was evaporated in vacuo to give 0.35 g
(75.2% yield) of 2. An analytical sample was obtained
by recrystallization from ethanol; as yellow crys-
tals, mp 116–117 C. IR: = 3100, 2990, 1700, 1680,
1
1580, and 1540 cm . 1H NMR (CDCl3): =1.10–
145 (m, 9H, 3 COOCH2CH3), 2.90 (t, J = 5.6 Hz,
2H, H-4), 3.70 (t, J = 5.6 Hz, 2H, H-5), 4.20 (q, J =
7.0 Hz, 2H, COOCH2CH3), 4.40 (q, J = 7.0 Hz, 2H,

282 Ahmed
SCHEME 1
COOCH2CH3), 4.45–4.60 (m, 4H, H-7, OCH2CH3).
13C NMR (CDCl3): = 13.88 (q, OCH2CH3), 14.08
(q, COOCH2CH3), 14.52 (q, NCOOCH2CH3), 26.34
(t, C-4), 40.97 (t, C-5), 42.41 (t, C-7), 60.76 (t,
COOCH2CH3), 61.46 (t, N COOCH2CH3), 66.82
(t, OCH2CH3), 112.02 (s, C-3), 122.32 (s, C-7a), 129.94
(s, C-3a), 150.95 (s, CO ester), 155.29 (s, N CO),
166.06 (s, C-2), 184.71 (s, CS). MS: m/z = 386 [M+].
C16H22N2O5S2 (386.49) calcd.: C, 49.72; H, 5.73; N,
7.24; S, 16.59. Found: C, 49.59; H, 5.65; N, 7.11, S,
16.44.
Ethyl 3-Amino-4-oxo-2-thioxo-1,3,4,5,6,8-hexa-
hydropyrido[40,30:4,5]thieno-[2,3-d]pyrimidine-
7(2H) carboxylate (3)
To a solution of 2 (0.77 g, 0.002 mol) in ethanol (10
ml), hydrazine hydrate 99% (0.8 g, 0.024 mol)) was
added and the mixture was stirred at room tempera-
ture for 30 h. The solid product that had formed was
collected by filtration, dried, and recrystallized from
dioxane. Yield: 0.5 g (76.9%) of 3 as yellow crystals,
mp 232–234 C. IR: = 3400, 3000, 2990, 1710, 1680,

Syntheses of Some New Azolopyrido[40,30:4,5]thieno[2,3-d]pyrimidines 283
SCHEME 2
1
1
H-6), 4.10 (q, J = 7.0 Hz, 2H, COOCH2CH3), 4.30
(s, 2H, H-8), 4.70 (s, 2H, NH2), 5.30 (s, 2H, NH2),
8.30 (s, 1H, NH). 13C NMR (DMSO-d6): = 14.60 (q,
COOCH2CH3), 26.10 (t-C-5), 40.20 (t, C-6), 42.10 (t,
C-8), 60.80 (t, COOCH2CH3), 112.20 (s, C-4a), 120.90
(s, C-8a), 129.10 (s, C-9a), 154.20 (s, C-2), 159.30
(s, C-4), 165.40 (s, CO). MS: m/z = 324 [M+].
C12H16N6O3S (324.36) calcd.: C, 44.43; H, 4.97; N,
25.90. Found: C, 44.55; H, 4.80; N, 25.80.
1640, and 1600 cm . H NMR (DMSO-d6): = 1.20
(t, J = 7.0 Hz, 3H, COOCH2CH3), 2.90 (t, J = 5.6 Hz,
2H, H-5), 3.60 (t, J = 5.6 Hz, 2H, H-6), 4.20 (q, J =
7.0 Hz, 2H, COOCH2CH3), 4.50 (s, 2H, H-8), 6.30–
6.50 (br, 2H, NH2). 13C NMR (DMSO-d6): = 14.56
(q, COOCH2CH3), 25.26 (t, C-5), 40.74 (t, C-6), 46.75
(t, C-8), 60.95 (t, COOCH2CH3), 113.30 (s, C-4a),
121.03 (s, C-8a), 128.28 (s, C-4b), 153.60 (s, C-2),
154.64 (CO ester), 161.63 (s, CO), 161.63 (s, C-9a),
168.83 (s, C S). MS: m/z = 326 [M+]. C12H14N4O3S2
(326.40) calcd.: C, 44.15; H, 4.32; N, 17.16. Found: C,
44.10; H, 4.22; N, 17.10.
Method B (from Compound 3). To a suspension
of 3 (0.32 g , 0.001 mol) in ethanol (10 ml), hydrazine
hydrate (99%, 5ml) was added and the mixture was
heated under reflux for 6 h. After cooling, the pre-
cipitate that had formed was collected by filtration,
dried, and recrystallized from ethanol. Yield: 0.24 g
(75.7%) of 4 as colorless crystals, mp 243–244 C. The
compound is identical in every respect with the com-
pound obtained by Method A.
Ethyl 3-Amino-2-hydrazino-4-oxo-3,5,6,8-tetra-
hydropyrido[40,30:4,5]thieno-[2,3d]pyrimidine-
7(4H)carboxylate (4)
Method A (from Compound 2). A solution of 2
(1 g, 0.0026 mol) and hydrazine hydrate 99% (10 ml)
in ethanol (30 ml) was heated under reflux for 3 h.
The solid product that had formed was , after cool-
ing, collected by filtration, dried, and recrystallized
from ethanol. Yield: 0.61 g (73.5%) of 4 as col-
orless crystals, mp 242–244 C. IR: = 3400, 3200,
Ethyl 3-Amino-10-oxo-3,8,9,10-tetrahydropyrido-
[40,30:4,5]thieno[2,3-d][1,2,4]triazolo[1,5-a]-
pyrimidine-7(6H)-carboxylate (5)
1
1
2850, 1700, 1680, and 1620 cm . H NMR (DMSO-
d6): = 1.30 (t, J = 7.0 Hz, 3H, COOCH2CH3), 2.80
(t, J = 5.6 Hz, 2H, H-5), 3.60 (t, J = 5.6 Hz, 2H,
A mixture of compound 4 (0.32 g, 0.001 mol)
and triethyl orthoformate 98%, d = 0.89 (0.2 ml,
0.0016 mol) in acetic acid (5 ml) was refluxed for

284 Ahmed
1
1580 cm . 1H NMR (DMSO-d6): = 1.20 (t, J = 7.0
40 min. The solution was then cooled to room
temperature and the resulting solid was collected
by filtration, washed with diethyl ether, dried,
and recrystallized from ethanol/dioxane. Yield:
0.2 g (60.6%) of 5 as colorless crystals, mp 260–
262 C (decom.). IR: ␯ = 3420, 3320, 3200, 2990,
Hz, 3H, COOCH2CH3), 2.90 (t, J = 5.6 Hz, 2H, H-6),
3.60 (t, J = 5.6 Hz, 2H, H-7 ), 4.10 (q, J = 7.0 Hz, 2H,
COOCH2CH3), 4.60 (s, 2H, H-9), 5.80 (s, 2H, NH2).
MS: m/z = 335 [M+]. C12H13N7O3S (335.34) calcd.: C,
42.98; H, 3.90; N, 29.23. Found: C, 42.90; H, 3.78; N,
29.11.
1
2950, 1710, 1680, 1640, 1600, and 1580 cm .
1H NMR (DMSO-d6): = 1.20 (t, J = 7.0 Hz, 3H,
COOCH2CH3), 2.90 (t, J = 5.6 Hz, 2H, H-9), 3.70
(t, J = 5.6 Hz, 2H, H-8), 4.10 (q, J = 7.0 Hz, 2H,
COOCH2CH3), 4.60 (s, 2H, H-6), 6.20 (s, 2H, NH2),
8.90 (s, 1H, H-2). 13C-NMR (DMSO-d6): = 14.20
(q, COOCH2CH3), 25.60 (t, C-9), 40.90 (t, C-8), 42.70
(s, C-6), 61.60 (t, COOCH2CH3), 114.60 (s, C-9b),
125.90 (s, C-9a), 130.40 (s, C-5a), 153.40 (s, C-2),
154.70 (s, C-10), 155.60 (s, C-4a), 159.80 (s, C-3a),
164.30 (s, CO ester). MS: m/z = 334 [M+].
C13H14N6O3S (334.35) calcd.: C, 46.69; H, 4.22; N,
25.13; S, 9.58. Found: C, 46.57; H, 4.31; N, 24.96; S,
9.43.
Ethyl 5-Oxo-1,2,3,6,7,9-hexahydroimidazo[1,2-a]-
pyrido[40,30:4,5]thieno[2,3-d]pyrimidine-8(5H)-
carboxylate (9)
To a solution of compound 2 (0.38 g, 0.001 mol)
in benzene (10 ml), 1,2-diaminoethane (0.09 g,
0.0015 mol) was added, and the mixture was heated
under reflux for 6 h. The precipitate that had formed
was, after cooling, collected by filtration, dried, and
recrystallized from ethanol. Yield: 0.25 g (80.6%)
of 9 as colorless crystals, mp 294–296 C. IR:
=
1
3100, 2990, 2940, 1750, 1710, 1680, and 1640 cm .
1H NMR (DMSO-d6): = 1.30 (t, J = 7.0 Hz, 3H,
COOCH2CH3), 2.80 (t, J = 5.6 Hz, 2H, H-6), 3.50–
3.70 (m, 4H, H-7, H-3), 4.10 (q, J = 7.0 Hz, 2H,
COOCH2CH3), 4.40 (t, J = 7.6 Hz, 2H, H-2), 4.50 (s,
2H, H-9), 9.05 (brs, 1H, NH). MS: m/z = 320 [M+].
C14H16N4O3S (320.38) calcd.: C, 52.48; H, 5.03; N,
17.48. Found: C, 52.31; H, 4.99; N, 17.37.
Ethyl 3-Amino-2-methyl-10-oxo-3,8,9,10-tetrahy-
dropyrido[40,30:4,5]thieno-[2,3-d][1,2,4]triazolo-
[1,5-a]pyrimidine-7(6H)-carboxylate (6)
A mixture of compound 4 (0.32 g, 0.001 mol) and
triethyl orthoacetate (0.18 g, 0.0014 mol) in acetic
acid (5 ml) was refluxed for 30 min. The solu-
tion was then cooled to room temprature and the
resulting solid was collected by filtration, washed
with diethyl ether, dried, and recrystallized from
ethanol/dioxane. Yield: 0.22 g (64.7%) of 6 as col-
orless crystals, mp 289–291 C. IR: = 3400, 3300,
Ethyl 5-Oxo-2,3,6,9-tetrahydro-5H-pyrido[40,30:
4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidine-
8(7H)-carboxylate (10)
1
3200, 3000, 2850, 1700, 1680, and 1600 cm .
To a solution of compound 2 (0.38 g, 0.001 mol) in
anhydrous pyridine (10 ml), aminoethanethiol hy-
drochloride (0.16 g, 0.0014 mol) was added and the
mixture was heated under reflux for 24 h. The solvent
was evaporated in vacuo, sodium hydroxide (aque-
ous solution, 10%, 10 ml) was added, and the result-
ing precipitate was collected by filtration, dried, and
recrystallized from ethanol. Yield: 0.21 g (63.6%) of
10 as colorless crystals, mp 174–176 C. IR: = 3000,
1H NMR (DMSO-d6): = 1.20 (t, J = 7.0 Hz, 2H,
COOCH2CH3), 2.40 (s, 3H, CH3), 3.00 (t, J = 5.6 Hz,
2H, H-9), 3.70 (t, J = 5.6 Hz, 2H, H-8), 4.10 (q,
J = 7.0 Hz, 2H, COOCH2CH3), 4.60 (s, 2H, H-6),
5.90 (s, 2H, NH2). MS: m/z = 348 [M+]. C14H16N6O3S
(348.39) calcd.: C, 48.26; H, 4.62; N, 24.12; S, 9.20.
Found: C, 48.39; H, 4.80; N, 24.27; S 9.28.
1
1
2980, 1700, 1680, and 1540 cm . H NMR (DMSO-
d6): = 1.20 (t, J = 7.0 Hz, 3H, COOCH2CH3), 2.80
(t, J = 5.6 Hz, 2H, H-6), 3.55–3.70 (m, 4H, H-7, H-3),
4.10 (q, J = 7.0 Hz, 2H, COOCH2CH3), 4.40 (t, J =
7.6 Hz, 2H, H-2), 4.60 (s, 2H, H-9). 13C-NMR (DMSO-
d6): = 14.15 (q, COOCH2CH3), 25.12 (t, C-6), 26.80
(t, C-2), 40.7 (t, C-7), 42.70 (s, C-9), 48.16 (t, C-3),
61.06 (t, COOCH2CH3), 117.48 (s, C-5a), 127.03 (s,
C-5b), 128.92 (s, C-9a), 154.70 (s, C-10a), 156.18 (s,
C-11a), 160.76 (s, C-5), 163.43 (s, CO ester). MS:
m/z = 337 [M+]. C14H15N3O3S2 (337.43) calcd.: C,
49.83; H, 4.48; N, 12.45; S, 19.00. Found: C, 49.75;
H, 4.31; N, 12.28; S, 19.12.
Ethyl 4-Amino-5-oxo-4,5,6,9-tetrahydropyrido
[40,30:4,5]thieno[3,2-e][1,2,3,4]-tetrazolo[1,5-a]-
pyrimidine-8(7H)-carboxylate (8)
To a stirred suspension of compound 4 (0.64 g,
0.002 mol) in a mixture of acetic acid (8 ml) and
water (6 ml) a solution of sodium nitrite (0.17 g,
0.002 mol) in water (6 ml) was added dropwise at
0 C. The mixture was left in the refrigerator for
12 h. and the precipitate that had formed was col-
lected by filtration, dried, and recrystallized from
DMF. Yield: 0.36 g (54.54%) of 8 as yellow crystals,
mp 192–194 C. IR: = 3300, 3000, 1700, 1670, and

Syntheses of Some New Azolopyrido[40,30:4,5]thieno[2,3-d]pyrimidines 285
with stirring at room temperature. The mixture was
then gently heated in an oil-bath at 100 C for 6 h
with continous stirring. Pyridine was removed in
vacuo and the residue dissolved in benzene (5 ml)
and diluted with petroleum ether bp 60–80 (20 ml).
The soild product that separated was collected by
filtration, dried, and recrystallized from ethyl ac-
etate (charcoal). Yield: 0.23 g (63.8%) of 14 as
faint yellow crystals, mp 183–184 C. IR: = 3350–
Ethyl 2-Amino-10-oxo-8,9-dihydro-10H-pyrido-
[40,30:4,5]thieno[2,3-d][1,3,4]-thiadiazolo[3,2-a]-
pyrimidine-7(6H)-carboxylate (12)
A mixture of compound 3 (0.32 g, 0.001 mol) and
cyanogen bromide (0.13 g, 0.0012 mol) in aqueous
ethanol 75% (8 ml) was refluxed for 3 h. The re-
action mixture was evaporated to one-fourth of its
volume and neutralized by the addition of a satu-
rated aqueous solution of sodium acetate. The solid
product that had formed was collected by filtra-
tion, dried, and recrystallized from ethanol. Yield:
0.26 g (75.5%) of 12 as colorless crystals, mp 233–
235 C. IR : = 3200–3300, 3000, 2900, 1700, 1680,
1
3250, 2900, 1710, 1670, 1620, 1140 (C S) cm .
1H-NMR (DMSO-d6): ␦ = 1.20 (t, J = 7.0 Hz, 3H,
COOCH2CH3), 2.90 (t, J = 5.6 Hz, 2H, H-9), 3.70
(t, J = 5.6 Hz, 2H, H-8), 4.90 (q, J = 7.0 Hz, 2H,
COOCH2CH3), 4.60 (s, 2H, H-6), 5.30 (s, 1H, NH).
MS: m/z = 368 [M+]. C13H12N4O3S2 (368.46) calcd.:
C, 42.37; H, 3.28; N, 15.20; S, 26.10. Found: C, 42.49;
H, 3.32; N, 15.33; S, 26.20.
1
and 1620 cm . 1H NMR (DMSO-d6): = 1.20 (t,
J = 7.0 Hz, 3H, COOCH2CH3), 2.90 (t, J = 5.6 Hz,
2H, H-9), 3.70 (t, J = 5.6 Hz, 2H, H-8), 4.10 (q,
J = 7.0 Hz, 2H, COOCH2CH3), 4.60 (s, 2H, H-6), 7.99
(br s, 2H, NH2). 13C NMR (DMSO-d6): = 14.40 (q,
COOCH2CH3), 25.10 (t, C-9), 40.80 (t, C-8), 42.80 (t,
C-6), 61.40 (t, CO2CH2CH3), 118.10 (s, C-9b), 128.80
(s, C-9a), 131.90 (s, C-5a), 150.50 (s, C-4a), 154.40
(s, C-2),161.40 (s, C-10), 166.90 (s, CO ester). MS:
m/z = 351 [M+]. C13H13N5O3S2 (351.40) calcd.: C,
44.43; H, 3.73; N, 19.92; S, 18.24. Found: C, 44.55;
H, 3.80; N, 19.78; S, 18.30.
Ethyl 2,10-Dioxo-6,7,8,9-tetrahydropyrido-
[40,30:4,5]thieno[2,3-d][1,3,4]-thiadiazolo[3,2-a]-
pyrimidine-7-carboxylate (15)
A solution of compound 3 (0.32 g, 0.001 mol) in
ethanol (10 ml) was treated with ethyl chlorofor-
mate (0.12 g, 0.0011 mol) dropwise with stirring.
The mixture was then heated at 70 C for 24 h. The
solution was evaporated to dryness and the residue
diluted with water. The solid product was collected
by filtration, washed with water, dried, and recrys-
tallized from ethanol/water. Yield: 0.28 g (81.1%)
Ethyl 2-Hydrazino-10-oxo-8,9-dihydro-10H-
pyrido[40,30:4,5]thieno[2,3-d]-[1,3,4]thiadiazolo-
[3,2-a]pyrimidine-7(6H)-carboxylate (13)
of 15 as colorless crystals, mp 111–113 C. IR :
=
To a solution of compound 3 (0.64 g, 0.002 mol) in
ethanol (15 ml) was added N-carbethoxyhydrazine
(0.22 g, 0.002 mol) and hydrochloric acid (0.26 ml).
The contents were refluxed for 10 h. Ethanol was
distilled off compeletly. On basification with 10%
sodium carbonate solution, the solid that sepa-
rated was collected by filtration, washed with water,
dried, and recrystallized from ethanol. Yield: 0.45 g,
(62.67%) of 13 as yellow crystals, mp 270–273 C
(melt with decom.). IR: = 3250, 3200, 3100, 3000,
1
3300, 3100, 3000, 2980, 1745, 1710, and 1685 cm .
1H NMR (DMSO-d6): = 1.20 (t, J = 7.0 Hz, 3H,
COOCH2CH3), 3.00 (t, J = 5.6 Hz, 2H, H-9), 3.60
(t, J = 5.6 Hz, 2H, H-8), 4.10 (q, J = 7.0 Hz, 2H,
COOCH2CH3), 4.60 (s, 2H, H-6), 8.90 (s, 1H, NH).
MS: m/z = 352 [M+]. C13H12N4O4S2 (352.40) calcd.:
C, 44.30; H, 3.43; N, 15.89. Found: C, 44.20; H, 3.51;
N, 15.80.
1
1
1700, 1685, and 1620 cm . H NMR (DMSO-d6):
= 1.20 (t, J = 7.0 Hz, 3H, COOCH2CH3), 2.70 (t,
J = 5.6 Hz, 2H, H-9), 3.70 (t, J = 5.6 Hz, 2H, H-8),
4.10 (q, J = 7.0 Hz, 2H, COOCH2CH3), 4.60 (s, 2H, H-
6), 5.80 (s, 2H, NH2), 8.50 (s, 1H, NH). MS: m/z = 366
[M+]. C13H14N6O3S2 (366.42) calcd.: C, 42.61; H, 3.85;
N, 22.93; S, 17.50. Found: C, 42.70; H, 3.92; N, 22.81;
S, 17.67.
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[1] Sharma, S.; Charles, E. S. Prog Drug Res 1982, 26,
9.
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Ethyl 2-Thioxo-10-oxo-6,7,8,9-tetrahydro pyrido-
[40,30:4,5]thieno[2,3-d][1,3,4]-thiadiazolo[3,2-a]-
pyrimidine-7-carboxylate (14)
A solution of 3 (0.32 g, 0.001 mol) in pyridine (5 ml)
was treated with carbon disulfide (1 ml) dropwise

286 Ahmed
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