Synthesis and structure of novel thieno[2,3-d]pyrimidine derivatives containing 1,3,4-oxadiazole moiety

Article abstract of DOI:10.1002/jccs.200900060

The reaction of 5-(1-pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidine carbohydrazide 5 with CS² in the presence of pyridine afforded the 6-(2,3-dihydro-2-mercapto-1,3,4-oxadiazol-5-yl)-4-methyl-5-(1-pyrrolyl) -2-phenylthieno[2,3-d]pyrimidine

Full text of DOI:10.1002/jccs.200900060

408
Journal of the Chinese Chemical Society, 2009, 56, 408-415
Synthesis and Structure of Novel Thieno[2,3-d]pyrimidine Derivatives
Containing 1,3,4-Oxadiazole Moiety
Yuh-Wen Ho* (
Department of Materials and Textiles, Nanya Institute of Technology, Jhongli, Taiwan 32091, R.O.C.
) and Maw-Cherng Suen (
)
The reaction of 5-(1-pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidine carbohydrazide 5 with CS2
in the presence of pyridine afforded the 6-(2,3-dihydro-2-mercapto-1,3,4-oxadiazol-5-yl)-4-methyl-5-
(1-pyrrolyl)-2-phenylthieno[2,3-d]pyrimidine 6, which reacted with methyl iodide in the presence of so-
dium methoxide to yield the 6-(2-methylthio-1,3,4-oxadiazol-5-yl)-4-methyl-5-(1-pyrrolyl)-2-phenyl-
thieno[2,3-d]pyrimidine 7. The 6-(2-substituted-1,3,4-oxadiazol-5-yl)-2-phenylthieno[2,3-d]pyrimidine
derivatives 9, 11 and 13 were obtained by the condensation of 6-(2-methylthio-1,3,4-oxadiazol-5-yl)-
2-phenylthieno[2,3-d]pyrimidine 7 with appropriate secondary amines. The structure of the new com-
pounds was substantiated from their IR, UV-vis spectroscopy, 1H NMR, mass spectra, elemental analysis
and X-ray crystal analysis.
Keywords: Thioxopyrimidine; 1,3,4-Oxadiazole; Thieno[2,3-d]pyrimidine; Spectral characteris-
tics; X-ray crystal structure.
INTRODUCTION
The considerable biological and medicinal activity of
RESULTS AND DISCUSSION
All relevant reactions are depicted in Schemes I-II.
The required compound 5-cyano-1,6-dihydro-4-methyl-
2-phenyl-6-thioxopyrimidine 1 was prepared by treating
benzoylisothiocyanate with 3-aminocrotononitrile in re-
fluxing dioxane.13,14 Cyclization of thioxopyrimidine 1
with ethyl chloroacetate 2 in DMF in the presence of excess
anhydrous potassium carbonate at room temperature gave
the ethyl 5-amino-4-methyl-2-phenylthieno[2,3-d]pyrimi-
dine-6-carboxylate 3 (Scheme I). The possible mechanism
for formation of compound 3 can be explained by the reac-
tion pathway depicted in Scheme I. Treatment of com-
pound 3 with 2,5-dimethoxytetrahydrofuran in glacial ace-
tic acid produced the ethyl 5-(1-pyrrolyl)-4-methyl-2-phen-
ylthieno[2,3-d]pyrimidine-6-carboxylate 4, which reacted
with an excess of 85% hydrazine hydrate in refluxing etha-
nol to give the corresponding 5-(1-pyrrolyl)-4-methyl-2-
phenylthieno[2,3-d]pyrimidine carbohydrazide 5 (Scheme
I). The carbohydrazide 5 was used as a key intermediate for
the synthesis of novel 1,3,4-oxadiazole-thieno[2,3-d]pyr-
imidine derivatives. The IR spectra of compound 4 indi-
cated the absence of the NH2 group and carbohydrazide 5
showed the characteristic absorption bands at 3398 and
3335 cm-1 for the NH2 group, at 3110 cm-1 for the NH group
fused thienopyrimidines have stimulated much research in
this field.1-5 Likewise, 1,3,4-oxadiazole (OXD) derivatives
are useful targets in the search for antivirals as they have
been associated with many types of biological properties
such as anti-inflammatory,6,7 antibacterial, antifungal ac-
tivities,8,9 and they inhibit HIV replication.10 The incorpo-
ration of two moieties increases biological activity of both
and thus it was of value to synthesize some new hetero-
cyclic derivatives having two moieties in the same mole-
cules.Our research has been devoted to the development of
new classes of pyrrolothienopyrimidine systems which in-
corporate the 1,3,4-oxadiazole moiety in the hope that they
may be biologically active. In preceding papers11,12 we
have described the synthesis of a series of novel 5-(1-pyr-
rolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidine deriva-
tives containing chalcones, pyridines, pyridin-2(1H)-ones,
2H-pyran-2-one, pyrazoles, pyrimidines imidazolpyrimi-
dines and pyrazolopyrimidine moiety. In continuation of
our studies, we describe the synthesis of some novel thieno-
[2,3-d]pyrimidine derivatives containing 1,3,4-oxadiazole
moiety derived from 5-(1-pyrrolyl)-4-methyl-2-phenyl-
thieno[2,3-d]pyrimidine carbohydrazide 5. The structures
of the new compounds were verified by spectroscopic
methods and the X-ray crystal structure of compound 9 is
also discussed.
and 1638 cm-1 for the C=O group. The H NMR spectra
1
(CDCl3) of compounds 4 and 5 revealed two multiplets at d
6.49-6.35 (2H, m) and 6.81-6.72 (2H, m), which were

Novel Thieno[2,3-d]pyrimidine Derivatives Containing
J. Chin. Chem. Soc., Vol. 56, No. 2, 2009 409
1,3,4-Oxadiazole Moiety
Scheme I
readily assigned to the hydrogen attached at C3, C4 and C2,
C5 of the pyrrolyl ring, respectively. Moreover, carbohy-
drazide 5 showed a broad singlet at d 6.42 (2H, br) assigned
to the NH2 protons and a broad singlet at d 9.72 (1H, br) as-
signed to the NH proton.
(Scheme I). The structures of 6 and 7 were established on
the basis of their elemental analysis and spectral data. On
the other hand, some novel 6-(2-substituted-1,3,4-oxadi-
azol-5-yl)-4-methyl-5-(1-pyrrolyl)-2-phenylthieno[2,3-
d]pyrimidine derivatives 9, 11 and 13 were also obtained
by the condensation reaction of compound 7 with mor-
pholine 8, 1,2,3,4-tetrahydroquinoline 10 and 1-(2-pyr-
imidyl)piperazine 12, respectively (Scheme II). Neverthe-
less, under the same reaction conditions, reaction of carbo-
hydrazide 5 with N,N-diphenylamine 14 did not produce
the desired compound 15, but led only to the recovery of
starting material. Typical proton chemical shift assignment
Next, cyclization of carbohydrazide 5 with CS2 in the
presence of pyridine afforded the 6-(2,3-dihydro-2-mer-
capto-1,3,4-oxadiazol-5-yl)-4-methyl-5-(1-pyrrolyl)-2-
phenylthieno[2,3-d]pyrimidine 6 followed by reaction with
iodomethane in the presence of sodium methoxide to yield
the 6-(2-methylthio-1,3,4-oxadiazol-5-yl)-4-methyl-5-(1-
pyrrolyl)-2-phenylthieno[2,3-d]pyrimidine 7 (84% yield)

410 J. Chin. Chem. Soc., Vol. 56, No. 2, 2009
Ho and Suen
Scheme II
for compound 11 is shown in Fig. 1. This structure gets fur-
ther support from mass spectroscopy. It has been observed
that electron impact (EI) spectral has many common fea-
tures. Compounds 9, 11 and 13 exhibited m/z 357, m/z 331,
m/z 315, m/z 288, m/z 260 and m/z 222 piece peaks. The
possible mass fragmentation pathway of compound 9 is
shown in Chart I.
vis absorption spectroscopy. The absorption maxima (lmax)
of the compounds 7, 9, 11 and 13 were measured in ethyl-
acetate and dichloromethane solutions and are shown in
Table 1. For compounds 7, 9, 11 and 13 in ethyl acetate, ab-
sorption maxima in the UV region was in the range of 339
to 356 nm, while in dichloromethane it was 343 to 366 nm.
It was also found that their lmax values show a significant
increase and are clearly bathochromic shifts when the sol-
vent polarity is increased from ethylacetate to dichloro-
methane, i.e. a positive solvatochromis, which shows that
the compounds molecules are more polar in the excited
state than the ground state.15,16 Compound 7, as a standard,
absorbed at 343 nm (dichloromethane) and substituent ef-
fects on the absorption maxima were evaluated compared
Furthermore, the absorption spectral characteristics
of the compounds 7, 9, 11 and 13 were also studied by UV/
with this value. The differences of these values are shown
CH 2 Cl 2
max
by Dl
. As is apparent in Table 1, all the compounds
were bathochromic shifts of 15 to 23 nm caused by intro-
duction of the stronger electron donating substituents (such
as morpholine, 1,2,3,4-tetrahydroquinoline and 1-((2-pyr-
imidyl)piperazine) into oxadiazol-thieno[2,3-d]pyrimidine
moiety at which there is an electron density decrease17 that
should produce a bathochromic shift of lmax. Moreover, the
spectroscopic data also demonstrate that the compound 9
Fig. 1. Typical proton chemical shift assignment for
compound 11.

Novel Thieno[2,3-d]pyrimidine Derivatives Containing
J. Chin. Chem. Soc., Vol. 56, No. 2, 2009 411
1,3,4-Oxadiazole Moiety
Chart I
(lmax 366 nm, dichloromethane) containing the morpho-
linyl group showed the largest bathochromic shift of 23
nm. In general, with respect to the substituents of com-
pounds 7, 9, 11 and 13, the compounds were bathochro-
mically shifted in the order: 9 > 13 > 11 > 7.
the conformation of the molecule. The relevant crystallo-
graphic date and structure refinement are given in Table 2.
The selected bond lengths and bond angles are listed in Ta-
ble 3. The hydrogen atoms were refined isotropically in
idealized positions riding on the atom to which they are at-
tached. The crystal system of compound 9 is monoclinic,
the space group is C 2/c and data was collected in the range
of 1.67 to 26.01°. Details of the intensity collection are
given in Table 2.
On the other hand, the suitable single crystals of com-
pound 9 were obtained by slow crystallization from chloro-
form at room temperature. Perspective view and the num-
bering of the atoms are depicted in Fig. 2. This drawing
clearly establishes the structural formula and also shows
The basal plane is formed by phenyl(C(18))-thieno-

412 J. Chin. Chem. Soc., Vol. 56, No. 2, 2009
Ho and Suen
Table 1. Absorption spectral date of 6-(2-substituted-1,3,4-oxadiazol-5-yl)-thieno[2,3-
d]pyrimidine derivatives (7, 9, 11 and 13)
CH
N
N
3
N
N
N
R
O
S
EtOAc
EtOAc
CH2Cl2
CH2Cl2
lmax
(nm)
emax
(mol-1 cm-1)
36192
lmax
åmax
CH2Cl2
Compd.
R
Dlmax
(nm)
(mol-1 cm-1)
71228
7
9
SCH3
339
354
343
366
-
N
O
27224
33680
23
N
11
13
340
23520
358
59280
15
N
N
N
N
356
38672
360
51440
17
EtOAc Measured in ethylacetate; CH Cl Measured in dichloromethane
2
2
Dlmax: Substituent effects in lmax
[2,3-d]pyrimidine(C(9)), thieno[2,3-d]pyrimidine(C(7))-
oxadiazole(C(6)) and oxadiazole(C(5))-morpholine (N(1))
atoms, with bond lengths of 1.473(4), 1.433(4) and 1.333(4)
Å, respectively. The morpholine moiety is in the trans (E)
configuration with respect to the S atom of the fused thieno-
[2,3-d]pyrimidine system (Fig. 2). Moreover, the fused
thieno[2,3-d]pyrimidine system is almost plannar, and due
to the effect of thieno[2,3-d]pyrimidine moiety, the phenyl
group exhibits a noticeable quinoid character that is dem-
onstrated by the shortening of the C(22)-C(23) [1.389(5)
Å] and C(19)-C(20) [1.370(4) Å] bond lengths compared
to the standard Car-Car distance of 1.397(1) Å.18 In addition,
the morpholine and thieno[2,3-d]pyrimidine moieties are
in a staggered conformation with respect to the nitrogen at-
oms giving rise to some angular distortion at C(5) and C(6)
[N(2)-C(5)-N(1) > O(2)-C(5)-N(1) and N(3)-C(6)-C(7) >
O(2)-C(6)-C(7)] (Table 3). Similar results are observed in
the case of thieno[2,3-d]pyrimidine and phenyl moieties
which resulted in angular distortion at C(9) [N(4)-C(9)-
C(18) > N(5)-C(9)-C(18)]. The C(5)-N(1) [1.333(4) Å]
bond is shorter than the C(6)-C(7) [1.433(4) Å], which is
probably due to the electron donating effect of the mor-
pholinly group. Also, the interesting torsion angles which
entirely define the molecule conformation are selected and
listed in Table 4.
Computation of the oxadiazole plane comprising at-
oms N(2), N(3), C(6), O(2) and C(5) show that the oxa-
diazole moiety is almost planar. The planarity is further
supported by the conformational angles N(2)-N(3)-C(6)-
O(2) (0.4°); N(3)-C(6)-O(2)-C(5) (0.8°); C(6)-O(2)-C(5)-
N(2) (-1.8°) and O(2)-C(5)-N(2)-N(3) (2.1°). Moreover,
the N(2)-C(5) [1.302(4) Å] bond is a little longer than the
N(3)-C(6) [1.291(3) Å]. The N(1)-C(3) morpholine ring
has a dihedral angle with an N(2)-N(3) 1,3,4-oxadiazole
ring of 15.3°, while the C(7)-S(1) thieno[2,3-d]pyrimidine
ring’s dihedral angle with this 1,3,4-oxadiazole is 1.8°.
Furthermore, the pyrrole ring attached to the thieno[2,3-
d]pyrimidine ring is not coplanar with this ring and makes a
Fig. 2. Perspective view of compound 9 with atomic
numbering.

Novel Thieno[2,3-d]pyrimidine Derivatives Containing
J. Chin. Chem. Soc., Vol. 56, No. 2, 2009 413
1,3,4-Oxadiazole Moiety
Table 2. Crystal data and structure refinement for compound 9
Table 3. Selected bond lengths [Å] and angles [°] for compound
9a
Empirical formula
Formula weight
Temperature
C25H22N6O2S
486.58
297(2) K
S(1)-C(7)
N(1)-C(3)
N(2)-C(5)
N(3)-C(6)
C(7)-C(12)
C(19)-C(20)
N(6)-C(16)
1.747(3) N(1)-C(5)
1.448(4) N(1)-C(2)
1.302(4) N(2)-N(3)
1.291(3) C(6)-C(7)
1.333(4)
1.475(4)
1.390(3)
1.433(4)
1.473(4)
1.389(5)
1.375(4)
1.349(5)
1.359(5)
129.4(3)
127.7(3)
130.2(3)
117.3(2)
121.8(2)
121.4(2)
Wavelength
0.71073 Å
Crystal system
Space group
Monoclinic
C 2/c
1.359(4) C(9)-C(18)
1.370(4) C(22)-C(23)
1.369(4) N(6)-C(13)
1.423(3) C(13)-C(14)
1.395(5) C(15)-C(16)
102.3(2) N(2)-C(5)-N(1)
117.7(2) N(3)-C(6)-C(7)
120.4(2) C(12)-C(7)-C(6)
116.8(2) N(4)-C(9)-C(18)
116.8(2) C(19)-C(18)-C(9)
Unit cell dimensions
a = 26.0462(14) Å
b = 13.6533(7) Å
c = 13.9836(8) Å
a = 90°
N(6)-C(12)
C(14)-C(15)
C(5)-O(2)-C(6)
N(1)-C(5)-O(2)
O(2)-C(6)-C(7)
C(6)-C(7)-S(1)
N(5)-C(9)-C(18)
b =110.9450(10)°
g = 90°
Volume
Z
4644.2(4) Å3
8
Density (calculated)
Absorption coefficient
Crystal size
1.392 Mg/m3
0.221 mm-1
0.60 ´ 0.59 ´ 0.31 mm
C(23)-C(18)-C(9) 120.1(2) C(5)-N(1)-C(2)
C(16)-N(6)-C(13) 109.2(2) C(13)-N(6)-C(12) 124.8(2)
C(14)-C(13)-N(6) 107.3(2) C(13)-C(14)-C(15) 108.3(2)
Theta range for data collection 1.67 to 26.01°
Index ranges
-32 £ h £ 31, -16 £ k £ 14,
-17 £ l £ 10
a Standard deviations in parentheses
Reflections collected
12895
Independent reflections
4564 [R(int) = 0.0263]
Table 4. Selected torsion angles for compound 9
Completeness to theta = 26.01° 99.8%
Absorption correction
Max. and min. transmission
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
Empirical
S(1)-C(7)-C(6)-N(3)
N(2)-C(5)-N(1)-C(3)
N(4)-C(9)-C(18)-C(23) -17° N(4)-C(9)-C(18)-C(19) 164.5°
C(13)-N(6)-C(12)-C(7) -82° C(13)-N(6)-C(12)-C(11) 97.1°
0.9° S(1)-C(7)-C(6)-O(2)
8.1° N(2)-C(5)-N(1)-C(2)
-179.7°
-164.3°
0.934 and 0.876
Full-matrix least-squares on F2
4564/0/312
1.373
Final R indices [I > 2 sigma(I)] R1 = 0.0672, wR2 = 0.2345
R indices (all data)
Largest diff. peak and hole
R1 = 0.0787, wR2 = 0.2526
1.050 and -0.654 e.Å-3
EXPERIMENTAL SECTION
All melting points are uncorrected and in °C. IR spec-
tra were recorded on a JASCO FTIR-3 spectrometer (KBr);
1H NMR spectra were obtained on a Bruker AM-300 WB
FI-NLR spectrometer, and chemical shifts are expressed in
d ppm using TMS as an internal standard. Electron impact
mass spectra were obtained at 70 eV using a Finingan Mat
TSQ-46C spectrometer. Microanalyses for C, H, and N
were performed on a Perkin-Elmer 240 elemental analyzer.
Electronic spectra were recorded on a Shimadzu UV 240
from compound solutions in ethyl acetate and dichloro-
methane at a concentration of 1.25 ´ 10-5 mol liter-1.
Ethyl 5-amino-4-methyl-2-phenylthieno[2,3-d]pyrimi-
dine-6-carboxylate (3)
dihedral angle of 98.1° with the thieno[2,3-d]pyrimidine
ring plane.
In conclusion, a novel synthesis of some new thieno-
[2,3-d]pyrimidine derivatives containing 1,3,4-oxadiazole
moiety were obtained by the condensation of 6-(2-meth-
ylthio-1,3,4-oxadiazol-5-yl)-2-phenylthieno[2,3-d]pyrim-
idine with appropriate secondary amines. The structures of
all new synthesized compounds were established from
their spectral data, elemental analysis and X-ray crystal
analysis. The solvatochromic behaviours and substituent
effects in ethyl acetate and dichloromethane solutions were
evaluated. The results indicated that the oxadiazol-thieno-
[2,3-d]pyrimidine derivatives show a significant increase
and are clearly bathochromic shifts with an increase in sol-
vent polarity. Moreover, the introduction of electron donat-
ing substituents into the oxadiazol-thieno[2,3-d]pyrimi-
dine moiety lmax shifts bathochromically in all solvents
used.
A mixture of 5-cyano-1,6-dihydro-4-methyl-2-phen-
yl-6-thioxopyrimidine 1 (2.27 g, 0.01 mol), potassium car-
bonate anhydrous (2.76 g, 0.02 mol) and ethyl chloro-
acetate 2 (1.23 g, 0.01 mol) in DMF (50 mL) was stirred at
room temperature for 4 h and then diluted with cold water
(50 mL). The resulting solid product was collected by fil-
tration, washed with water and recrystallized from ethyl ac-

414 J. Chin. Chem. Soc., Vol. 56, No. 2, 2009
Ho and Suen
etate/ethanol to give 2.88 g of pale yellow needles (92%
yield), mp 177 °C; IR: n 3488, 3359 (NH2), 1663 (CO)
cm-1; 1H NMR (CDCl3): d 1.41 (3H, t, J = 4.80 Hz, CH3),
2.98 (3H, s, CH3), 4.37 (2H, q, J = 3.0 Hz, OCH2), 6.23
(2H, br, NH2), 8.55-8.53, 7.53-7.48 (5H, m, phenyl-H); MS
(m/z, %): 313 (M+,100). Anal. Calcd. for C16H15N3O2S: C,
61.34; H, 4.79; N, 13.41. Found: C, 61.23; H, 4.70; N,
13.41%.
bondisulphide (5 mL) in pyridine (10 mL) was refluxed on
a steam bath for 6 h. After cooling, the resultant solid prod-
uct was collected by filtration, washed with water and re-
crystallized from ethanol to give 3.67 g of greenish yellow
crystals (94% yield), mp 276 °C; IR: n 1625 (C=N), 1182
(C=S) cm-1; MS (m/z, %): 391 (M+, 100). Anal. Calcd. for
C19H13N5OS2: C, 58.31; H, 3.32; N, 17.90. Found: C,
58.33; H, 3.23; N, 17.77%.
Ethyl 5-(1-pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]-
pyrimidine-6-carboxylate (4)
6-(2-Methylthio-1,3,4-oxadiazol-5-yl)-4-methyl-5-(1-
pyrrolyl)-2-phenylthieno[2,3-d]pyrimidine (7)
A mixture of ethyl 5-amino-4-methyl-2-phenylthieno-
[2,3-d]pyrimidine-6-carboxylate 3 (3.13 g, 0.01 mol) and
2,5-dimethoxytetrahydrofuran (1.26 g, 0.01 mol) in glacial
acetic acid (20 mL) was refluxed for 12 h. After cooling,
the resultant solid product was collected by filtration and
washed with water, and the crude product recrystallized
from ethanol/glacial acetic acid gave 3.16 g of gray white
needles (87% yield), mp 165 °C; IR: n 1697 (CO) cm-1; 1H
NMR (CDCl3): d 1.15 (3H, t, J = 2.0 Hz, CH3), 2.18 (3H, s,
CH3), 4.18 (2H, q, J = 2.0 Hz, OCH2), 6.35 (2H, m, 3,4-H
of pyrrolyl), 6.72 (2H, m, 2,5-H of pyrrolyl), 8.48-8.46,
7.43-7.42 (5H, m, phenyl-H); MS (m/z, %): 363 (M+, 83),
334 (82), 316 (100), 288 (58), 278 (38), 214 (2), 185 (14),
160 (10), 116 (9), 77 (9), 51 (5). Anal. Calcd. for
C20H17N3O2S: C, 66.11; H, 4.68; N, 11.57. Found: C,
66.13; H, 4.72; N, 11.45%.
To a mixture of compound 6 (0.39 g, 1 mmol) in
methanol (10 mL) and sodium methoxide (0.08 g, 1.5
mmol), iodomethane (0.17 g, 1.2 mmol) was added. After
stirring at room temperature for 24 h, the resultant solid
product was collected by filtration, washed with water and
recrystallized from THF to give 0.34 g of pale yellow crys-
tals (84% yield), mp 215 °C; IR: n 1625 (C=N) cm-1; 1H
NMR (CF3COOD): d 2.53 (3H, s, CH3), 2.93 (3H, s,
SCH3), 6.23 (2H, m, 3,4-H of pyrrolyl), 7.08 (2H, m, 2,5-H
of pyrrolyl), 8.44, 7.76-7.73 (5H, m, phenyl-H); MS (m/z,
%): 405 (M+, 100), 358 (12), 331 (38), 315 (20), 304 (53),
289 (18), 261 (8), 244 (2), 198 (10), 151 (4), 103 (3), 75
(4). Anal. Calcd. for C20H15N5OS2: C, 59.25; H, 3.70; N,
17.28. Found: C, 59.13; H, 3.55; N, 17.33%.
6-(2-Substituted-1,3,4-oxadiazol-5-yl)-4-methyl-5-(1-
pyrrolyl)-2-phenylthieno[2,3-d]pyrimidine derivatives
(9, 11 and 13) General procedure:
4-Methyl-5-(1-pyrrolyl)-2-phenylthieno[2,3-d]pyrimi-
dine carbohydrazide (5)
A mixture of compound 7 (0.405 g, 1 mmol) and ex-
cess secondary amines 8, 10 and 12 (morpholine, 1,2,3,4-
tetrahydroquinoline and 1-((2-pyrimidyl)piperazine) (5
mmol) was refluxed for 10 h and poured into ice-water, and
the precipitated product was collected by filtration, washed
with water, and the crude product recrystallized from chlo-
roform/THF.
A mixture of compound 4 (3.63 g, 0.01 mol) and
hydrazine hydrate (10 mL, 85% solution) was refluxed in
absolute ethanol (20 mL) for 24 h. After cooling, the resul-
tant solid product was collected by filtration and washed
with water, and the crude product recrystallized from etha-
nol to give 3.42 g of gray white needles (98% yield), mp
230 °C; IR: n 3398, 3335 (NH2), 3110 (NH), 1638 (CO)
cm-1; 1H NMR (CDCl3): d 2.10 (3H, s, CH3), 6.46 (2H, br,
NH2), 6.49 (2H, m, 3,4-H of pyrrolyl), 6.81 (2H, m, 2,5-H
of pyrrolyl), 8.46-8.44, 7.43-7.41 (5H, m, phenyl-H), 9.72
(1H, br, NH); MS (m/z, %): 349 (M+, 39), 318 (100), 289
(9), 277 (26), 244 (8), 212 (2), 187 (6), 160 (8), 116 (9), 104
(5), 77 (7), 69 (2). Anal. Calcd. for C18H15N5OS: C, 61.89;
H, 4.29; N, 20.05. Found: C, 61.84; H, 4.22; N, 20.15%.
6-(2,3-Dihydro-2-mercapto-1,3,4-oxadiazol-5-yl)-4-
methyl-5-(1-pyrrolyl)-2-phenyl-thieno[2,3-d]pyrimidine
(6)
6-(2-Morpholinyl-1,3,4-oxadiazol-5-yl)-4-methyl-5-(1-
pyrrolyl)-2-phenylthieno[2,3-d]pyrimidine (9)
Yield 90%, mp 281 °C; IR: n 1611 (C=N) cm-1; 1H
NMR (CDCl3): d 2.52 (3H, s, CH3), 3.86 (4H, d, J = 1.0 Hz,
2,6-H of morpholinyl), 4.17 (4H, d, J = 1.0 Hz, 3,5-H of
morpholinyl), 6.78 (2H, m, 3,4-H of pyrrolyl), 7.10 (2H, m,
2,5-H of pyrrolyl), 8.49-8.47, 7.90-7.86 (5H, m, phenyl-
H); MS (m/z, %): 444 (100), 387 (1), 357 (35), 331 (10),
315 (11), 301 (81), 288 (8), 275 (1), 262 (1), 222 (12), 196
(8), 164 (2), 151 (4), 117 (12), 68 (16). Anal. Calcd. for
C23H20N6O2S: C, 62.16; H, 4.50; N, 18.91. Found: C,
62.29; H, 4.41; N, 19.01%.
A mixture of compound 5 (0.35 g, 1 mmol) and car-

Novel Thieno[2,3-d]pyrimidine Derivatives Containing
J. Chin. Chem. Soc., Vol. 56, No. 2, 2009 415
1,3,4-Oxadiazole Moiety
6-(2-Quinolizinyl-1,3,4-oxadiazol-5-yl)-4-methyl-5-(1-
pyrrolyl)-2-phenylthieno[2,3-d]pyrimidine (11)
may be obtained free of charge via http://www.ccdc.cam.
ac.uk or from The Director, CCDC, 12 Union Road, Cam-
bridge CB2 1EZ, UK (fax: +441223/336-033; e-mail: de-
posit@ccdc.cam.ac.uk).
Yield 56%, mp 185 °C; IR: n 1602 (C=N) cm-1; 1H
NMR (CDCl3): d 2.01-1.98 (2H, m, 3-H of quinolizinyl),
2.24 (3H, s, CH3), 2.81 (2H, t, J = 1.28 Hz, 4-H of quino-
lizinyl), 3.72 (2H, t, J = 1.25 Hz, 2-H of quinolizinyl), 6.45
(2H, m, 3,4-H of pyrrolyl), 6.84 (2H, m, 2,5-H of pyrrolyl),
7.01-6.98 (1H, m, 6-H of quinolizinyl), 7.08 (1H, d, J = 1.0
Hz, 5-H of quinolizinyl), 7.19-7.16 (1H, m, 7-H of quino-
lizinyl), 7.64 (1H, d, J = 1.0 Hz, 8-H of quinolizinyl),
8.55-8.53, 7.50-7.48 (5H, m, phenyl-H); MS (m/z, %): 490
(100), 438 (5), 405 (44), 358 (18), 331 (41), 315 (52), 302
(60), 288 (28), 278 (10), 261 (11), 245 (39), 198 (22), 160
(29), 128 (20), 133 (78), 117 (7), 77 (4). Anal. Calcd. for
C28H22N6OS: C, 68.57; H, 4.48; N, 17.14. Found: C, 68.88;
H, 4.59; N, 17.38%.
ACKNOWLEDGEMENT
We are grateful to the National Science Council of
Taiwan for their financial support.
Received October 17, 2008.
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Yield 58%, mp 307 °C; IR: n 1606 (C=N) cm-1; 1H
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X-ray structure study of compound 9
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