5-(1-Pyrrolyl)-2-phenylthieno[2,3-d]pyrimidine as building block in heterocyclic synthesis: Novel synthesis of some pyrazoles, pyrimidines, imidazo[1,2-a]pyrimidines, pyrazolo[1,5-a]pyrimidines, pyrido-(pyrimido) pyrazolo[1,5-a]pyrimidines, 1,2,4-triazolo

Article abstract of DOI:10.1002/jccs.200700154

Treatment of enaminone derivative 6-(3-dimethylamino-acryloyl)-5-(1- pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidine 1 with appropriate hydrazine compounds 2a,b in refluxing ethanol afforded the corresponding 6-(1-substituted-pyrazol-5-yl)-2-phenylthie

Full text of DOI:10.1002/jccs.200700154

Journal of the Chinese Chemical Society, 2007, 54, 1075-1085
1075
5-(1-Pyrrolyl)-2-phenylthieno[2,3-d]pyrimidine as Building Block in
Heterocyclic Synthesis: Novel Synthesis of Some Pyrazoles, Pyrimidines,
Imidazo[1,2-a]pyrimidines, Pyrazolo[1,5-a]pyrimidines, Pyrido-
(pyrimido)pyrazolo[1,5-a]pyrimidines, 1,2,4-Triazolo[1,5-a]pyrimidine and a
1,2,3,4-Tetrazolo[1,5-a]pyrimidine Derivative
Yuh-Wen Ho (
Department of Textile Science, Nanya Institute of Technology, Chung-Li, Taiwan, 32034, R.O.C.
)
Treatment of enaminone derivative 6-(3-dimethylamino-acryloyl)-5-(1-pyrrolyl)-4-methyl-2-phen-
ylthieno[2,3-d]pyrimidine 1 with appropriate hydrazine compounds 2a,b in refluxing ethanol afforded the
corresponding 6-(1-substituted-pyrazol-5-yl)-2-phenylthieno[2,3-d]pyrimidines 3a,b. Cyclization of
enaminone derivative 1 with appropriate guanidine compounds 13a-c in the presence of a basic catalyst
yields the corresponding 6-(2-substituted-pyrmidin-6-yl)-2-phenylthieno[2,3-d]pyrimidines 15a-c. The
compound 15c can be cyclized with appropriate a-halogenocarbonyl compounds 16a-d to afford the cor-
responding 6-(2-substituted-imidazo[1,2-a]pyrimidin-7-yl)-2-phenylthieno[2,3-d]pyrimidines 17a-d.
On the other hand, the pyrazolo[1,5-a]pyrimidines 20a-c, pyrido(pyrimido)[2,3:4,3]pyrazolo[1,5-a]py-
rimidines 22a-c, pyrido[4,5:4,3]pyrazolo[1,5-a]pyrimidine 24, 1,2,4-triazolo[1,5-a]pyrimidine 26a, and
1,2,3,4-tetrazolo[1,5-a]pyrimidine derivative 26b were also obtained by the intramolecular cyclization of
enaminone derivative 1 with appropriate 5(3)-amino-pyrazole derivatives 18a-c, 21a-c, 23, 3-amino-
1,2,4-triazole 25a and 5-amino-1H-tetrazole 25b under acid conditions, respectively.
Keywords: Pyrrolothieno[2,3-d]pyrimidine; Pyrazoles; Pyrimidines; Imidazo[1,2-a]pyrimidines;
Pyrazolo[1,5-a]pyrimidines; Pyrido(pyrimido)pyrazolo[1,5-a]pyrimidines;
1,2,4-Triazolo[1,5-a]pyrimidine; 1,2,3,4-Tetrazolo[1,5-a]pyrimidine derivatives.
INTRODUCTION
The considerable biological and medicinal activity of
derivative 6-(3-dimethylamino-acryloyl)-5-(1-pyrrolyl)-
4-methyl-2-phenylthieno[2,3-d]pyrimidine 1 for the syn-
thesis of various pyrazoles, pyrimidines, imidazo[1,2-a]-pyr-
imidines, pyrazolo[1,5-a]pyrimidines, pyrido(pyrimido)-
[2,3:4,3]pyrazolo[1,5-a]pyrimidines, pyrido[4,5:4,3]pyr-
azolo[1,5-a]pyrimidine 1,2,4-triazolo[1,5-a]pyrimidine,
and a 1,2,3,4-tetrazolo[1,5-a]pyrimidine derivative incor-
porating a 5-(1-pyrrolyl)-4-methyl-2-phenyl-thieno[2,3-
d]pyrimidine moiety.
fused thienopyrimidines have stimulated much research in
this field.1-8 The incorporation of two moieties increases bi-
ological activity of both and thus it was of value to synthe-
size some new heterocyclic derivatives having two moi-
eties in the same molecules. Our research has been devoted
to the development of new classes of heterocycle systems
which incorporate the pyrrolothienopyrimidine moiety in
the hope that they may be biologically active. In preceding
papers9,10 we have described the synthesis of pyrido-
[3’,2’:4,5]thieno[3,2-d]pyrimidines, pyrido[3’,2’:4,5]thi-
eno[2,3-e]-1,2,4-triazolo[1,5-c]pyrimidines and pyrimido-
[2,3:4,3]pyrazolo[1,5-a]pyrimidines. More recently, a se-
ries of Schiff’s bases, chalcones, pyridines, pyridin-2(1H)-
ones and 2H-pyran-2-one derivatives containing a 5-(1-
pyrrolyl)-4-methyl-2-phenyl-thieno[2,3-d]pyrimidine
moiety were reported from our laboratory.11 In continua-
tion of our studies, we report herein the use of enaminone
RESULTS AND DISCUSSION
All relevant reactions are depicted in Schemes I-III.
6-(3-Dimethylamino-acryloyl)-5-(1-pyrrolyl)-4-methyl-2-
phenylthieno[2,3-d]pyrimidine 1, which is required as a
starting material, was prepared as previously reported.11
Several pyrrolothienopyrimidines substituted at position-6
with different heterocyclic residues were obtained via treat-
ment of enaminone derivative 1 with different reagents.

1076 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Ho
Scheme I
Scheme II

Pyrrolylphenylthieno[2,3-d]pyrimidine Derivatives
J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 1077
Scheme III
Thus, reaction of 6-(3-dimethylamino-acryloyl)-5-(1-pyr-
rolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidine 1 with
appropriate hydrazine compounds 2a,b in refluxing etha-
nol afforded the corresponding 6-(1-substituted-pyrazol-
5-yl)-2-phenylthieno[2,3-d]pyrimidines 3a,b (Scheme I).
The structures of 3a,b were established on the basis of their
elemental analysis and spectral data. The IR spectra of
compounds 3a,b indicated the absence of the C=O group

1078 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Ho
absorption band, indicating the formation of pyrazole de-
rivatives 3a,b. In addition, the 1H NMR spectra (CDCl3) of
compounds 3a,b revealed two doublets at d 5.27-5.15 (1H,
d) and 7.73-7.22 (1H, d), which were readily assigned to
the hydrogen attached at C4 and C3 of the pyrazole ring, re-
spectively. The formation of compounds 3a,b would in-
volve an initial addition of the amino group in hydrazine
compounds 2a,b to the activated double bond in enaminone
derivative 1, followed by deamination, to form the interme-
diate 3’, which then undergoes cyclization and aromatiza-
tion via loss of water17 affording the final products 3a,b.
Nevertheless, the enaminone derivative 1 was cyclized
with hydrazine compound 2c-e under different conditions
to form a tetracyclic compound. Thus, it has been found
that enaminone derivative 1 with hydrazine compound 2c
in refluxing glacial acetic acid gave the 11-methyl-6-oxo-
9-phenyl-pyrimido[3’,2’:4,5]thieno[2,3-f]pyrrolo[1,2-
a]azepine 4 (Scheme I). The oxopyrimido[3’,2’:4,5]thi-
eno[2,3-f]pyrrolo[1,2-a]azepine 4 was assumed to be
formed via addition of an amino group in hydrazine com-
pound 2c to the activated double bond in enaminone deriv-
ative 1, followed by deamination, to form the intermediate
4’, which followed by dehydration, and subsequent nucleo-
philic cyclization with loss of hydrazine compound affords
the final product 4. The IR spectra of compound 4 indicated
the characteristic absorption band at 1710 cm-1 for the C=O
group. In particular, the 1H NMR spectra (CDCl3) of com-
pound 4 revealed four doublets at d 6.44 (1H, d), 6.92 (1H,
d), 7.47 (1H, d) and 7.50 (1H, d) which were readily as-
signed to the hydrogen attached at C3, C4, C5, and C1 of the
oxopyrimido[3’,2’:4,5]thieno[2,3-f]pyrrolo[1,2-a]azepine
ring, respectively, and a triplet at d 6.69 (1H, t) assigned to
the hydrogen attached at C2 of the oxopyrimido[3’,2’:4,5]-
thieno[2,3-f]pyrrolo[1,2-a]azepine ring, was also con-
firmed by the mass spectrum m/z 343 (M+, 52). The struc-
ture of compound 4 was further confirmed from an inde-
pendent synthesis of compound 4 by the reacting of enami-
none derivative 1 in glacial acetic acid/hydrochloride (1:1)
under reflux to afford a product indentical in all respects
(mp., mixed mp., TLC and spectra). Also, enaminone de-
rivative 1 reacted with 2d-e to yield product 4 under the
same reaction conditions.
drate (Scheme II). Junjappa et al.12 have also reported an
analogous reaction in their papers. The a-ketoketene di-
thioacetal derivative 6 was prepared from compound 511
following the method in the literature.13 The structure of
pyrazole derivative 7 was established on the basis of their
elemental analysis and spectral data. The 1H NMR spectra
(CDCl3) of compound 7 revealed an ethoxycarbonyl (d
1.28 (3H, s) and 4.02 (2H, q)) groups and a singlet at d 5.51
(1H, s) assigned to the hydrogen attached at C4 of the pyr-
azole ring, was also confirmed by the mass spectrum m/z
401 (M+, 35). The mass fragmentation pattern of compound
7 showed the presence of the ion peaks [M-CH3]+ at m/z
386, [M-CH2CH3]+ at m/z 372 and [M-OCH2CH3]+ at m/z
356.
Next, reaction of enaminone derivative 1 with thio-
urea 8 in refluxing DMF/ethanol in the presence of excess
anhydrous potassium carbonate afforded the 6-(2-mercap-
to-pyrimidin-6-yl)-2-phenylthieno[2,3-d]pyrimidine 9
1
(Scheme II). The H NMR spectra (DMSO-d6) of com-
pound 9 revealed two doublets at d 5.12 (1H, d) and 7.88
(1H, d) which were readily assigned to the hydrogen at-
tached at C5 and C4 of the pyrimidine ring, respectively, and
a singlet at d 3.07 (1H, s) assigned to the -SH attached at C2
of the pyrimidine ring was also confirmed by the mass
spectrum m/z 401 (M+, 100). Nevertheless, when enami-
none derivative 1 was reacting with thiourea 8 under simi-
lar reaction conditions, except that DMF/ethanol was re-
placed by 2-methoxyethanol to give the 6-(2-methoxyeth-
ylthio-pyrimidin-6-yl)- 2-phenylthieno[2,3-d]pyrimidine
10. The structure of pyrimidine derivative 10 was estab-
lished on the basis of their elemental analysis and spectral
1
data. The H NMR spectra (CDCl3) of compound 10 re-
vealed two triplets at d 4.60 (2H, t) and 3.84 (2H, t) which
were readily assigned to the -SCH2CH2- protones and a sin-
glet at d 2.28 (3H, s) assigned to the methoxy protones was
also confirmed by the mass spectrum m/z 459 (M+, 10). The
mass fragmentation pattern of compound 10 showed the
presence of the ion peaks [M-CH3]+ at m/z 444, [M-OCH3]+
at m/z 428, [M-CH2OCH3]+ at m/z 414, [M-CH2CH2OCH3]+
at m/z 400 and [M-SCH2CH2OCH3]+ at m/z 368. Under the
same reaction conditions, reaction of enaminone derivative
1 with methylthiourea 11 did not produce the desired com-
pound 12, but led only to the recovery of starting material
(Scheme III).
Furthermore, the 6-(5-ethoxy-pyrazol-3-yl)-2-phen-
ylthieno[2,3-d]pyrimidine 7 was obtained by treatment of
6-(3,3-bis(methylthio)-2-propen-1-one)-2-phenylthieno-
[2,3-d]pyrimidine 6 in refluxing ethanol in the presence of
an equimolar amount of sodium ethoxide and hydrazine hy-
On the other hand, the study was extended to investi-
gate the behavior of enaminone derivative 1 with different
nucleophiles like guanidine and aminopyrazole derivatives

Pyrrolylphenylthieno[2,3-d]pyrimidine Derivatives
J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 1079
with a view to synthesizing various heterocyclic ring sys-
tems. Intramolecular cyclization of enaminone derivative 1
gave different products depending on reaction conditions.
Thus, treatment of enaminone derivative 1 with guanidine
compound 13a-c in refluxing 2-methoxyethanol in the
presence of excess anhydrous potassium carbonate af-
forded the corresponding 6-(2-substituted-pyrimidin-6-
yl)-2-phenylthieno[2,3-d]pyrimidine 15a-c (Scheme III).
The structures of pyrimidine derivatives 15a-c were estab-
lished on the basis of their elemental analysis and spectral
data. The 1H NMR spectra (CDCl3) of compound 15a re-
vealed two doublets at d 6.10 (1H, d) and 7.75 (1H, d)
which were readily assigned to the hydrogen attached at C5
and C4 of the pyrimidine ring, respectively, and a singlet at
d 9.20 (1H, s) assigned to the hydrogen attached at C2 of the
pyrimidine ring. The formation of compound 15 would in-
volve an initial addition of the amino group in compound
13 to the activated double bond in enaminone derivative 1,
followed by deamination, to form the compound 14, which
then undergoes intramolecule cyclization via loss of water
at d 6.62-5.65 (1H, d) and 8.84-8.63 (1H, d) which were
readily assigned to the hydrogen attached at C3 and C2 of
the pyrazolo[1,5-a]pyrimidine ring, respectively. In addi-
tion, compound 20a and 20c revealed a sharp singlet at d
8.74 (1H, s) and at d 4.60 (2H, s), which were assigned to
the hydrogen and the CNCH2- protons at C7 of the pyra-
zolo[1,5-a]pyrimidine ring, respectively. Finally, under the
same reaction conditions, cyclocondensation of the enami-
none derivative 1 with 3-amino-4,6-disubstituted-pyra-
zolo[3,4-d]pyridine derivatives 21a-b, 3-amino-4-meth-
yl-6-phenyl-pyrazolo[3,4-d]pyrimidine 21c, 3-amino-4,6-
dihydroxy-pyrazolo[4,3-c]pyridine 23, 3-amino-1,2,4-tri-
azole 25a and 5-amino-1H-tetrazole 25b afforded the cor-
responding pyrido(pyrimido)[2,3:4,3]pyrazolo[1,5-a]pyr-
imidines 22a-c, pyrido[4,5:4,3]pyrazolo[1,5-a]pyrimidine
24, 1,2,4-triazolo[1,5-a]pyrimidine 26a, and 1,2,3,4-tetra-
zolo[1,5-a]pyrimidine derivative 26b, respectively (Scheme
IV). The structures of compounds 22a-c, 24 and 26a,b were
established on the basis of their elemental analysis and
spectral data. The 1H NMR (CF3COOD) spectra of com-
pound 22a revealed two doublets at d 7.36 (1H, d) and 8.28
(1H, d) which were readily assigned to the hydrogen at-
tached at C3 and C2 of the pyrido[2,3:4,3]pyrazolo[1,5-
a]pyramidine ring and a sharp singlet at d 7.46 (1H, s),
which was assigned to the hydrogen at C9 of the pyrido-
[2,3:4,3]pyrazolo[1,5-a]pyramidine ring.
1
affording the final product 15a. The H NMR spectra of
compound 15b-c are similar to compound 15a. Further-
more, when aminopyrimidine derivative 15c was allowed
to cyclocondensate with appropriate a-halogenocarbonyl
compounds 16a-c under reflux in DMF/ethanol, it afforded
the corresponding 6-(2-substituted-imidazo[1,2-a]pyri-
midin-7-yl)-2-phenylthieno[2,3-d]pyramidines 17a-d. The
1H NMR spectra (CDCl3) of compound 17a-c revealed two
doublets at d 5.58-5.40 (1H, d) and 8.13-8.01 (1H, d) which
were readily assigned to the hydrogen attached at C6 and C5
of the imidazo[1,2-b]pyrimidine ring, respectively, and a
singlet at d 6.92-6.60 (1H, s) was assigned to the hydrogen
at C3 of the imidazo[1,2-b]pyrimidine ring. Compound 17c
revealed a methylene (d 5.19 (2H, s)) and ethoxycarbonyl
(d 1.27 (3H, t) and 4.25 (2H, q)) groups.
In conclusion, 6-(3-dimethylamino-acryloyl)-5-(1-pyr-
rolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidine 1 has
been shown to be a useful building block for the synthesis
of some new pyrazoles, pyrimidines, imidazo[1,2-b]pyr-
imidines, pyrazolo[1,5-a]pyrimidines, pyrido(pyrimido)-
pyrazolo[1,5-a]pyrimidine derivatives, 1,2,4-triazolo[1,5-
a]pyrimidine, and 1,2,3,4-tetrazolo[1,5-a]pyrimidine de-
rivative.
On the other hand, the 6-[(7,8-disubstituted)-pyrazolo-
[1,5-a]pyrimidin-4-yl]-2-phenylthieno[2,3-d]pyramidine
derivatives 20a-c were obtained by intramolecular cycliza-
tion of enaminone derivative 1 with 5-amino-3,4-disubsti-
tuted-pyrazoles 18a-c in refluxing glacial acetic acid
(Scheme III). Abu Elmaati et al.16 have also reported an
analogous reaction in their papers. The mechanisms of
compounds 20a-c are similar to compound 15a-c. The IR
spectra of compounds 20a-c indicated the characteristic ab-
sorption bands at 2205-2194 cm-1 for the CºN group. The
1H NMR spectra of compound 20a-c revealed two doublets
EXPERIMENTAL SECTION
All melting points were determined in a capillary tube
and are uncorrected. The IR spectra were recorded on po-
tassium bromide pellets on a JASCO FTIR-3 spectrometer.
1
The H NMR spectra were obtained on a Bruker AM-
300WB FT-NMR spectrometer and chemical shifts are ex-
pressed in d ppm using TMS as an internal standard. Elec-
tron impact mass spectra were obtained at 70 eV by using a
Finnigan Mat TSQ-46C spectrometer. Microanalyses for

1080 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Ho
Scheme IV
C, H, and N were performed on a Perkin-Elmer 240 ele-
mental analyzer. 5-Amino-3,4-disubstituted-pyrazoles
18a-c, 3-amino-4,6-disubstituted-pyrazolo[3,4-d]pyridine
derivatives 21a-b, 3-amion-4-methyl-6-phenyl-pyrazolo-
[3,4-d]pyrimidine 21c, and 3-amino-4,6-dihydroxy-pyra-
zolo[4,3-c]pyridine 23 were prepared following the meth-
ods in the literature,14,10,15 respectively.
6-(1-Methyl-pyrazol-5-yl)-5-(1-pyrrolyl)-4-methyl-2-
phenylthieno[2,3-d]pyrimidine (3b)
This compound was synthesized from compound 1
(0.39 g, 1 mmol) and methylhydrazine 2b (0.05 g, 1 mmol)
in a manner similar to that described for the preparation of
3a. It was recrystallized from ethanol/THF to give 0.36 g of
yellow crystals (98% yield), mp 148 °C; 1H NMR (CDCl3):
d 2.25 (3H, s, CH3), 3.93 (3H, s, N-CH3), 5.27 (1H, d, J =
1.0 Hz, 4-H of pyrazole), 6.46 (2H, t, 3,4-H of pyrrolyl),
6.81 (2H, t, 2,5-H of pyrrolyl), 7.22 (1H, d, J = 1.0 Hz, 3-H
of pyrazole), 8.55-8.53, 7.52-7.49 (5H, m, phenyl-H); MS:
371 (M+, 100), 357 (8), 302 (3), 253 (3), 226 (10), 198 (7),
143 (3), 125 (11), 103 (44), 77 (30), 51 (7).
6-(Pyrazol-5-yl)-5-(1-pyrrolyl)-4-methyl-2-phenylthieno-
[2,3-d]pyrimidine (3a)
A mixture of 6-(3-dimethylamino-acryloyl)-5-(1-pyr-
rolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidine 1 (0.39
g, 1 mmol) and an excess of hydrazine hydrate 2a (4 mL,
85% solution 4 mmol) was refluxed in absolute ethanol (10
mL) for 7 h. After cooling, the resulting solid product was
collected by filtration, washed with water and recrystal-
lized from ethanol to give 0.28 g of gray white crystals
(78% yield), mp 279 °C; IR: n 3224 (NH) cm-1; 1H NMR
(CDCl3): d 2.14 (3H, s, CH3), 5.15 (1H, d, J = 1.0 Hz, 4-H
of pyrazole), 6.42 (2H, t, 3,4-H of pyrrolyl), 7.03 (2H, t,
2,5-H of pyrrolyl), 7.73 (1H, d, J = 1.0 Hz, 3-H of pyra-
zole), 8.47-8.45, 7.53-7.52 (5H, m, phenyl-H), 13.29 (1H,
s, NH); MS: 357 (M+, 100), 329 (8), 315 (4), 253 (6), 226
(8), 185 (5), 111 (5), 103 (17), 77 (13).
Anal. Calcd. for C21H17N5S: C, 67.92; H, 4.58; N,
18.86. Found: C, 67.88; H, 4.52; N, 18.59%.
11-Methyl-6-oxo-9-phenyl-pyrimido[3’,2’:4,5]thieno-
[2,3-f]pyrrolo[1,2-a]azepine (4)
Method A
A mixture of 6-(3-dimethylamino-acryloyl)-5-(1-pyr-
rolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidine 1 (0.39
g, 1 mmol) and acetyl hydrazine 2c (0.08 g, 1 mmol) was
refluxed in glacial acid (8 mL) for 12 h. After cooling, the
resulting solid product was collected by filtration, washed
with water and recrystallized from ethanol to give 0.18 g of
greenish yellow crystals (52% yield), mp 189 °C; IR: n
Anal. Calcd. for C20H15N5S: C, 67.22; H, 4.20; N,
19.60. Found: C, 67.13; H, 4.23; N, 19.77%.

Pyrrolylphenylthieno[2,3-d]pyrimidine Derivatives
J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 1081
1
1710 (CO) cm-1; H NMR (CDCl3): d 2.66 (3H, s, CH3),
mp 103 °C; 1H NMR (CDCl3): d 1.28 (3H, t, J = 2.1 Hz,
CH3), 2.11 (3H, s, CH3), 4.02 (2H, q, J = 2.0 Hz, OCH2),
5.51 (1H, s, 4-H of pyrazole), 6.40 (2H, m 3,4-H of pyr-
rolyl), 6.82 (2H, m, 2,5-H of pyrrolyl), 8.55-8.51, 7.51-
7.45 (5H, m, phenyl-H), 8.62 (1H, br, NH); MS: 401 (M+,
35), 386 (4), 372 (10), 356 (5), 347 (32), 330 (100), 316
(18), 304 (10), 290 (34), 251 (5), 226 (10), 185 (12), 160
(8), 129 (5), 103 (40), 77 (37), 51 (10).
6.44 (1H, d, J = 1.8 Hz, 3-H of pyrimidothienopyrrolo-
azepine), 6.69 (1H, t, J = 1.24 Hz, 2-H of pyrimidothieno-
pyrroloazepine), 6.92 (1H, d, J = 1.0 Hz, 4-H of pyrimido-
thienopyrroloazepine), 7.47 (1H, d, J = 1.3 Hz, 5-H of pyri-
midothienopyrroloazepine), 7.50 (1H, d, J = 1.0 Hz, 1-H of
pyrimidothienopyrroloazepine), 8.60-8.58, 7.55-7.54 (5H,
m, phenyl-H); MS: 343 (M+, 52), 315 (100), 288 (1), 223
(7), 211 (58), 179 (18), 153 (9), 140 (4), 103 (34), 77 (29),
51 (9).
Anal. Calcd. for C22H19N5OS: C, 65.83; H, 4.74; N,
17.45. Found: C, 65.56; H, 4.72; N, 17.32%.
Anal. Calcd. for C20H13N3OS: C, 69.97; H, 3.79; N,
12.24. Found: C, 70.10; H, 3.90; N, 12.36%.
6-(2-Mercapto-pyrimidin-6-yl)-5-(1-pyrrolyl)-4-methyl-
2-phenylthieno[2,3-d]pyrimidine (9)
Method B
A mixture of 6-(3-dimethylamino-acryloyl)-5-(1-pyr-
rolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidine 1 (0.39
g, 1 mmol) and acetyl hydrazine 2c (0.08 g, 1 mmol) was
refluxed in glacial acid/HCl (10 mL) for 4 h. The mixture
was poured into ice-water, and the precipitated product was
collected by filtration, washed with water, and the crude
product recrystallized to give 0.25 g (74% yield).
A mixture of compound 1 (0.39 g, 1 mmol), thiourea 8
(0.08 g, 1 mmol) and excess anhydrous potassium carbon-
ate (0.28 g, 2 mmol) was refluxed in DMF/ethanol (10 mL)
for 20 h and poured into ice-water, acidified with hydro-
chloric acid and the precipitated product was collected by
filtration, washed with water, and the crude product recrys-
tallized from chloroform/ethanol to give 0.16 g of yellow-
1
ish brown crystals (40% yield), mp > 300 °C; H NMR
6-(3,3-Bis(methylthio)-2-propen-1-one)-5-(1-pyrrolyl)-
4-methyl-2-phenylthieno[2,3-d]pyrimidine (6)
(DMSO-d6): d 2.1 (3H, s, CH3), 3.07 (1H, s, SH), 5.12 (1H,
d, J = 1.0 Hz, 5-H of pyrimidinyl), 6.47 (2H, m, 3,4-H of
pyrrolyl), 7.13 (2H, m, 2,5-H of pyrrolyl), 7.88 (1H, d, J =
1.0 Hz, 4-H of pyrimidinyl), 8.48-8.45, 7.55-7.54 (5H, m,
phenyl-H); MS: 401 (M+, 100).
This compound was prepared following the methods in
the literature.13 It was recrystallized from acetone/THF to
give 3.09 g of yellow crystals (93% yield), mp 90 °C; IR: n
1701 (CO) cm-1; 1H NMR (CDCl3): d 2.17 (3H, s, SCH3),
2.20 (3H, s, SCH3), 2.28 (3H, s, CH3), 6.47 (2H, m, 3,4-H
of pyrrolyl), 6.87 (2H, m, 2,5-H of pyrrolyl), 7.46 (1H, s,
COCH=), 8.57-8.54, 7.52-7.46 (5H, m, phenyl-H); MS:
437 (M+, 16), 422 (10), 390 (50), 375 (6), 343 (4), 333
(100), 318 (29), 290 (32), 244 (5), 223 (7), 184 (22), 160
(18), 107 (10), 103 (62), 91 (50), 77 (43), 51 (12).
Anal. Calcd. for C21H15N5S2: C, 62.84; H, 3.74; N,
17.45. Found: C, 62.53; H, 3.42; N, 17.68%.
6-(2-Methoxyethylthio-pyrimidin-6-yl)-5-(1-pyrrolyl)-4-
methyl-2-phenylthieno[2,3-d]pyrimidine (10)
A mixture of compound 1 (0.39 g, 1 mmol), thiourea 8
(0.08 g, 1 mmol) and excess anhydrous potassium carbon-
ate (0.28 g, 2.0 mmol) was refluxed in 2-methoxyethanol
(10 mL) for 20 h and poured into ice-water, acidified with
hydrochloric acid and the precipitated product was col-
lected by filtration, washed with water, and the crude prod-
uct recrystallized from ethanol/THF to give 0.41 g of pale
yellow crystals (90% yield), mp 165 °C; 1H NMR (CDCl3):
d 2.28 (3H, s, OCH3), 3.47 (3H, s, CH3), 3.84 (2H, t, J = 1.0
Hz, CH2), 4.60 (2H, t, J = 1.0 Hz, CH2), 5.83 (1H, d, J = 1.0
Hz, 5-H of pyrimidinyl), 6.54 (2H, t, 3,4-H of pyrrolyl),
6.82 (2H, t, 2,5-H of pyrrolyl), 8.35 (1H, d, J = 1.0 Hz, 4-H
of pyrimidinyl), 8.57-8.53, 7.52-7.50 (5H, m, phenyl-H);
MS: 459 (M+, 10), 444 (100), 428 (2), 414 (8), 400 (16),
368 (36), 356 (68), 343 (59), 313 (12), 291 (56), 238 (4),
Anal. Calcd. for C22H19N3OS3: C, 60.41; H, 4.34; N,
9.61. Found: C, 60.55; H, 4.52; N, 9.59%.
6-(5-Ethoxy-pyrazol-3-yl)-5-(1-pyrrolyl)-4-methyl-2-
phenylthieno[2,3-d]pyrimidine (7)
A mixture of compound 6 (0.44 g, 1 mmol) and so-
dium ethoxide (0.07 g, 1 mmol) in refluxing ethanol (10
mL) for 15 minutes and hydrazine hydrate (10 mL) was
added. The mixture was refluxed for 6 h and poured into
ice-water, acidified with hydrochloric acid and the precipi-
tated product was collected by filtration, washed with wa-
ter, and the crude product recrystallized from chloroform/
ethanol to give 0.38 g of pale yellow crystals (94% yield),

1082 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Ho
211 (5), 160 (4), 77 (14).
preparation of 15a. It was recrystallized from ethanol/THF
to give 0.33 g of yellow crystals (87% yield), mp 288 °C;
IR: n 3243 (NH2) cm-1; 1H NMR (CDCl3): d 2.70 (3H, s,
CH3), 6.02 (1H, d, J = 2.0 Hz, 5-H of pyrimidinyl), 6.77
(2H, t, 3,4-H of pyrrolyl), 6.96 (2H, t, 2,5-H of pyrrolyl),
8.21 (1H, d, J = 1.0 Hz, 4-H of pyrimidinyl), 8.34-8.33,
7.86-7.77 (5H, m, phenyl-H); MS: 384 (M+, 100), 368 (11),
350 (12), 342 (10), 315 (5), 290 (9), 238 (2), 211 (4), 192
(10), 178 (15), 103 (5), 77 (6).
Anal. Calcd. for C24H21N5OS2: C, 62.74; H, 4.57; N,
15.25. Found: C, 62.69; H, 4.60; N, 15.48%.
6-(Pyrimidin-6-yl)-5-(1-pyrrolyl)-4-methyl-2-phenyl-
thieno[2,3-d]pyrimidine (15a)
A mixture of compound 1 (0.39 g, 1 mmol), formami-
dine hydrochloride 13a (0.08 g, 1 mmol) and excess anhy-
drous potassium carbonate (0.28 g, 2.0 mmol) was refluxed
in 2-methoxyethanol (10 mL) for 24 h. After cooling, the
resulting solid product was collected by filtration, washed
with ethanol and water, and the crude product recrystal-
lized from from THF/ethanol to give 0.32 g of yellow crys-
tals (86% yield), mp 242 °C; 1H NMR (CDCl3): d 2.29 (3H,
s, CH3), 6.10 (1H, d, J = 1.0 Hz, 5-H of pyrimidinyl), 6.56
(2H, t, 3,4-H of pyrrolyl), 6.84 (2H, t, 2,5-H of pyrrolyl),
7.75 (1H, d, J = 1.2 Hz, 4-H of pyrimidinyl), 8.57-8.53,
7.52-7.48 (5H, m, phenyl-H), 9.20 (1H, s, 2-H of pyrimi-
dinyl); MS: 369 (M+, 100), 343 (10), 336 (5), 289 (16), 265
(10), 238 (11), 211 (10), 185 (14), 142 (6), 104 (36), 160
(4), 77 (33).
Anal. Calcd. for C21H16N6S: C, 65.62; H, 4.17; N,
21.87. Found: C, 65.73; H, 4.30; N, 21.79%.
6-(2-Methyl-imidazo[1,2-a]pyrimidin-7-yl)-5-(1-pyr-
rolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidine (17a)
A mixture of compound 15c (0.38 g, 1 mmol) and chlo-
roacetone 16a (0.1 g, 1 mmol) in DMF/ethanol (10 mL)
was refluxed overnight and then evaporated to dryness un-
der reduced pressure. The residue was washed with ether
and recrystallized from ethanol/THF to give 0.35 g of
greenish yellow crystals (82% yield), mp 260 °C; 1H NMR
(DMSO-d6 + CDCl3): d 2.14 (3H, s, CH3), 2.50 (3H, s,
CH3), 5.40 (1H, d, J = 1.0 Hz, 6-H of imidazopyrimidinyl),
6.42 (2H, t, 3,4-H of pyrrolyl), 6.60 (1H, s, 3-H of imidazo-
pyrimidinyl), 6.90 (2H, t, 2,5-H of pyrrolyl), 8.01 (1H, d, J
= 1.0 Hz, 5-H of imidazopyrimidinyl), 8.47-8.45, 7.46-7.45
(5H, m, phenyl-H); MS: 422 (M+, 10), 384 (100), 343 (5),
290 (8), 238 (3), 211 (7), 178 (10), 104 (4), 77 (5).
Anal. Calcd. for C21H15N5S: C, 68.29; H, 4.06; N,
18.97. Found: C, 68.33; H, 4.26; N, 18.88%.
6-(2-Methyl-pyrimidin-6-yl)-5-(1-pyrrolyl)-4-methyl-2-
phenylthieno[2,3-d]pyrimidine (15b)
This compound was synthesized from compound 1
(0.39 g, 1 mmol) and acetamidine hydrochloride 13b (0.10
g, 1.0 mmol) in a manner similar to that described for the
preparation of 15a. It was recrystallized from ethanol/THF
to give 0.29 g of pale yellow crystals (75% yield), mp 265
°C; 1H NMR (CDCl3): d 2.25 (3H, s, CH3), 2.74 (3H, s,
CH3), 5.90 (1H, d, J = 2.0 Hz, 5-H of pyrimidinyl), 6.53
(2H, t, 3,4-H of pyrrolyl), 6.84 (2H, t, 2,5-H of pyrrolyl),
8.42 (1H, d, J = 1.0 Hz, 4-H of pyrimidinyl), 8.54-8.52,
7.49-7.48 (5H, m, phenyl-H); MS: 383 (M+, 100), 368 (1),
340 (4), 289 (4), 238 (4), 211 (7), 192 (11), 171 (4), 104 (5),
93 (7), 77 (4).
Anal. Calcd. for C24H18N6S: C, 68.24; H, 4.26; N,
19.90. Found: C, 68.33; H, 4.13; N, 20.11%.
6-(2-Phenyl-imidazo[1,2-a]pyrimidin-7-yl)-5-(1-pyrrolyl)-
4-methyl-2-phenylthieno[2,3-d]pyrimidine (17b)
This compound was synthesized from compound 15c
(0.38 g, 1 mmol) and 2-bromoacetophenone 16b (0.20 g, 1
mmol) in a manner similar to that described for the prepara-
tion of 17a. It was recrystallized from ethanol/THF to give
0.37 g of yellow crystals (77% yield), mp 276 °C; 1H NMR
(DMSO-d6): d 2.18 (3H, s, CH3), 5.41 (1H, d, J = 1.0 Hz,
6-H of imidazopyrimidinyl), 6.47 (2H, t, 3,4-H of
pyrrolyl), 6.92 (1H, s, 3-H of imidazopyrimidinyl), 7.11
(2H, t, 2,5-H of pyrrolyl), 8.13 (1H, d, J = 1.0 Hz, 5-H of
imidazopyrimidinyl), 8.50-8.47, 7.57-7.55 (5H, m,
phenyl-H); MS: 484 (M+,100), 451 (100), 380 (2), 353 (3),
250 (2), 242 (38), 169 (6), 116 (6), 77 (7).
Anal. Calcd. for C22H17N5S: C, 68.93; H, 4.44; N,
18.27. Found: C, 68.73; H, 4.30; N, 18.38%.
6-(2-Amino-pyrimidin-6-yl)-5-(1-pyrrolyl)-4-methyl-2-
phenylthieno[2,3-d]pyrimidine (15c)
This compound was synthesized from compound 1
(0.39 g, 1 mmol) and guanidine hydrochloride 13c (0.10 g,
1.0 mmol) in a manner similar to that described for the
Anal. Calcd. for C29H20N6S: C, 71.90; H, 4.13; N,
17.35. Found: C, 71.99; H, 4.25; N, 17.48%.

Pyrrolylphenylthieno[2,3-d]pyrimidine Derivatives
J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 1083
6-(2-Carbethoxymethyl-imidazo[1,2-a]pyrimidin-7-yl)-
5-(1-pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimi-
dine (17c)
6.62 (1H, d, J = 1.0 Hz, 3-H of pyrazolopyrimidinyl), 6.74
(2H, t, 3,4-H of pyrrolyl), 6.92 (2H, t, 2,5-H of pyrrolyl),
8.34-8.27, 7.83-7.66 (5H, m, phenyl-H), 8.74 (1H, s, 7-H of
pyrazolopyrimidinyl), 8.84 (1H, d, J = 1.0 Hz, 2-H of
pyrazolopyrimidinyl); MS: 433 (M+, 36), 407 (1), 367 (1),
312 (5), 288 (16), 236 (7), 211 (15), 185 (5), 119 (20), 104
(100), 77 (79).
This compound was synthesized from compound 15c
(0.38 g, 1 mmol) and 4-chloroacetoacetic acid ethyl ester
16c (0.17 g, 1 mmol) in a manner similar to that described
for the preparation of 17a. It was recrystallized from etha-
nol/THF to give 0.21 g of brown crystals (43% yield), mp
181 °C; IR: n 1711 (C=O) cm-1; 1H NMR (CDCl3): d 1.27
(3H, t, J = 1.5 Hz, CH3), 2.24 (3H, s, CH3), 4.25 (2H, q, J =
1.5 Hz, OCH2), 5.19 (1H, s, CH2), 5.58 (1H, d, J = 1.0 Hz,
6-H of imidazopyrimidinyl), 6.50 (2H, t, 3,4-H of pyr-
rolyl), 6.61 (1H, s, 3-H of imidazopyrimidinyl), 6.82 (2H, t,
2,5-H of pyrrolyl), 8.11 (1H, d, J = 1.0 Hz, 5-H of imidazo-
pyrimidinyl), 8.55-8.53, 7.50 (5H, m, phenyl-H); MS: 494
(M+, 10), 477 (1), 422 (2), 412 (6), 384 (100), 3692 (8), 341
(7), 315 (4), 290 (7), 211 (4), 179 (7), 119 (3), 104 (6), 83
(7), 77 (12).
Anal. Calcd. for C24H15N7S: C, 66.51; H, 3.46; N,
22.63. Found: C, 66.33; H, 3.33; N, 22.49%.
6-(8-Cyano-7-methyl-pyrazolo[1,5-a]pyrimidin-4-yl)-5-
(1-pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidine
(20b)
This compound was synthesized from compound 1
(0.39 g, 1 mmol) and 5-amino-4-cyano-3-methyl-pyrazole
18b (0.11 g, 1 mmol) in a manner similar to that described
for the preparation of 20a. It was recrystallized from
DMF/glacial acid to give 0.29 g of light yellow crystals
(65% yield), mp 320 °C; IR: n 2195 (CºN) cm-1; 1H NMR
(CF3COOD): d 2.42 (3H, s, CH3), 2.64 (3H, s, CH3), 6.61
(1H, d, J = 1.0 Hz, 3-H of pyrazolopyrimidinyl), 6.94 (2H,
t, 3,4-H of pyrrolyl), 6.98 (2H, t, 2,5-H of pyrrolyl), 8.41-
8.33, 7.90-7.74 (5H, m, phenyl-H), 8.83 (1H, d, J = 1.0 Hz,
2-H of pyrazolopyrimidinyl); MS: 447 (M+, 36), 432 (2),
406 (2), 326 (5), 288 (10), 223 (8), 211 (14), 185 (6), 142
(5), 133 (16), 104 (100), 77 (72).
Anal. Calcd. for C27H22N6O2S: C, 65.59; H, 4.45; N,
17.00. Found: C, 65.71; H, 4.29; N, 17.18%.
6-(2-Biphenyl-imidazo[1,2-a]pyrimidin-7-yl)-5-(1-pyr-
rolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidine (17d)
This compound was synthesized from compound 15c
(0.38 g, 1 mmol) and 2-bromo-4¢-phenylacetophenone 16d
(0.28 g, 1 mmol) in a manner similar to that described for
the preparation of 17a. It was recrystallized from ethanol/
THF to give 0.21 g of deep yellow crystals (38% yield), mp
304 °C;1H NMR (DMSO-d6 + CDCl3): d 2.15 (3H, s, CH3),
5.43 (1H, d, J = 1.0 Hz, 6-H of imidazopyrimidinyl), 6.46
(2H, t, 3,4-H of pyrrolyl), 6.77 (1H, s, 3-H of imidazopyr-
imidinyl), 6.90 (2H, t, 2,5-H of pyrrolyl), 8.47-8.42, 8.02-
7.37 (15H, m, 5-H of imidazopyrimidinyl and phenyl-H);
MS: 560 (M+, 100), 483 (1), 425 (1), 397 (9), 384 (4), 280
(20), 192 (3), 181 (9), 152 (10), 77 (7).
Anal. Calcd. for C25H17N7S: C, 67.11; H, 3.80; N,
21.92. Found: C, 67.26; H, 3.99; N, 22.01%.
6-(8-Cyano-7-cyanomethyl-pyrazolo[1,5-a]pyrimidin-4-
yl)-5-(1-pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]pyrim-
idine (20c)
This compound was synthesized from compound 1
(0.39 g, 1 mmol) and 5-amino-3-cyanomethyl-4-cyano-
pyrazole 18c (0.13 g, 1 mmol) in a manner similar to that
described for the preparation of 20a. It was recrystallized
from DMF/ethanol to give 0.21 g of brownish yellow crys-
tals (45% yield), mp 230 °C; IR: n 2205 (CºN) cm-1; 1H
NMR (DMSO-d6): d 2.30 (3H, s, CH3), 4.60 (2H, s, CH2),
5.65 (1H, d, J = 1.0 Hz, 3-H of pyrazolopyrimidinyl), 6.46
(2H, t, 3,4-H of pyrrolyl), 7.07 (2H, t, 2,5-H of pyrrolyl),
8.51-8.49, 7.51-7.48 (5H, m, phenyl-H), 8.63 (1H, d, J =
1.0 Hz, 2-H of pyrazolopyrimidinyl); MS: 472 (M+, 100),
447 (4), 432 (18), 421 (3), 406 (4), 368 (2), 326 (10), 315
(22), 290 (50), 275 (9), 236 (22), 211 (24), 179 (18), 131
(12), 103 (61), 77 (64).
Anal. Calcd. for C35H24N6S: C, 75.00; H, 4.28; N,
15.00. Found: C, 75.38; H, 4.19; N, 15.28%.
6-(8-Cyano-pyrazolo[1,5-a]pyrimidin-4-yl)-5-(1-pyr-
rolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidine (20a)
A mixture of compound 1 (0.39 g, 1 mmol) and 5-ami-
no-4-cyano-pyrazole 18a (0.1 g, 1 mmol) was refluxed in
glacial acid (8 mL) for 12 h. After cooling, the resulting
solid product was collected by filtration, washed with wa-
ter and recrystallized from DMF/glacial acid to give 0.29 g
of light yellow crystals (67% yield), mp 275 °C; IR: n 2194
(CºN) cm-1 ;1H NMR (CF3COOD): d 2.35 (3H, s, CH3),
Anal. Calcd. for C26H16N8S: C, 66.10; H, 3.39; N,

1084 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
23.72. Found: C, 66.26; H, 3.59; N, 23.47%.
Ho
similar to that described for the preparation of 20a. It was
recrystallized from DMF/glacial acid to give 0.43 g of light
yellow crystals (78% yield), mp 315 °C; 1H NMR
(CF3COOD): d 2.88 (3H, s, CH3), 3.31 (3H, s, CH3), 6.63
(2H, m, 3,4-H of pyrrolyl), 6.91 (2H, m, 2,5-H of pyrrolyl),
7.25 (1H, d, J = 1.0 Hz, 3-H of pyrimidopyrazolopyrimi-
dinyl), 8.15 (1H, d, J = 1.0 Hz, 2-H of pyrimidopyrazolo-
pyrimidinyl), 8.22-8.20, 8.07-7.51 (10H, m, phenyl-H);
MS: 550 (M+, 8), 484 (4), 344 (72), 315 (15), 237 (6), 225
(100), 160 (2), 103 (12), 77 (6).
6-(8,10-Dimethyl-pyrido[2,3:4,3]pyrazolo[1,5-a]pyrimi-
din-4-yl)-5-(1-pyrrolyl)-4-methyl-2-phenylthieno[2,3-
d]pyrimidine (22a)
This compound was synthesized from compound 1
(0.39 g, 1 mmol) and 3-amino-4,6-dimethyl-pyrazolo[3,4-
b]pyridine 21a (0.23 g, 1 mmol) in a manner similar to that
described for the preparation of 20a. It was recrystallized
from DMF/glacial acid to give 0.41 g of orange crystals
(85% yield), mp 294 °C; 1H NMR (CF3COOD): d 2.91 (3H,
s, CH3), 2.99 (3H, s, CH3), 3.05 (3H, s, CH3), 6.82 (2H, t,
3,4-H of pyrrolyl), 7.02 (2H, t, 2,5-H of pyrrolyl), 7.36 (1H,
d, J = 1.0 Hz, 3-H of pyridopyrazolopyrimidinyl), 7.46
(1H, s, 9-H of pyridopyrazolopyrimidinyl), 8.28 (1H, d, J =
1.5 Hz, 2-H of pyridopyrazolopyrimidinyl), 8.37-8.35,
7.74-7.66 (5H, m, phenyl-H); MS: 487 (M+, 6), 421 (2),
344 (2), 322 (12), 315 (5), 215 (3), 187 (8), 173 (16), 162
(100), 119 (10), 77 (10).
Anal. Calcd. for C32H22N8S: C, 69.82; H, 4.00; N,
20.36. Found: C, 69.98; H, 4.26; N, 20.21%.
6-(8,10-Dihydroxy-pyrido[4,5:4,3]pyrazolo[1,5-a]pyri-
midin-4-yl)-5-(1-pyrrolyl)-4-methyl-2-phenylthieno[2,3-
d]pyrimidine (24)
This compound was synthesized from compound 1
(0.39 g, 1 mmol) and 3-amino-4,6-dihydroxy-pyrazolo-
[4,3-c]pyridine 23 (0.17 g, 1 mmol) in a manner similar to
that described for the preparation of 20a. It was recrys-
tallized from DMF/glacial acid to give 0.42 g of brown
crystals (86% yield), mp > 330 °C; IR: n 3350 (OH) cm-1;
1H NMR (CF3COOD): d 2.70 (3H, s, CH3), 6.52 (2H, m,
3,4-H of pyrrolyl), 6.87 (2H, m, 2,5-H of pyrrolyl), 7.19
(1H, d, J = 1.0 Hz, 3-H of pyridopyrazolopyrimidinyl),
7.84-7.81, 7.72-7.69 (6H, m, 7-H of pyridopyrazolopyrimi-
dinyl and phenyl-H), 8.39 (1H, d, J = 1.0 Hz, 2-H of pyri-
dopyrazolopyrimidinyl); MS: 491 (M+, 68), 474 (33), 402
(2), 392 (6), 343 (20), 315 (45), 288 (68), 236 (15), 224
(68), 211 (32), 166 (26), 153 (18), 104 (98), 77 (100).
Anal. Calcd. for C26H17N7O2S: C, 63.54; H, 3.46; N,
19.96. Found: C, 63.42; H, 3.26; N, 20.11%.
Anal. Calcd. for C28H21N7S: C, 68.99; H, 4.31; N,
20.12. Found: C, 69.18; H, 4.06; N, 20.01%.
6-(8,10-Diphenyl-pyrido[2,3:4,3]pyrazolo[1,5-a]pyrimi-
din-4-yl)-5-(1-pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]-
pyrimidine (22b)
This compound was synthesized from compound 1
(0.39 g, 1 mmol) and 3-amino-4,6-diphenyl-pyrazolo[3,4-
b]pyridine 21b (0.35 g, 1 mmol) in a manner similar to that
described for the preparation of 20a. It was recrystallized
from DMF/glacial acid to give 0.43 g of light yellow crys-
tals (71% yield), mp 340 °C; 1H NMR (CF3COOD): d 2.82
(3H, s, CH3), 6.78 (2H, t, 3,4-H of pyrrolyl), 7.07 (2H, t,
2,5-H of pyrrolyl), 7.37 (1H, d, J = 1.0 Hz, 3-H of pyrido-
pyrazolopyrimidinyl), 8.17 (1H, d, J = 1.0 Hz, 2-H of
pyridopyrazolopyrimidinyl), 8.40-8.37, 8.15-7.16 (16H,
m, 9-H of pyridopyrazolopyrimidinyl and phenyl-H); MS:
611 (M+, 10), 545 (2), 343 (3), 333 (12), 286 (100), 257
(15), 128 (11), 103 (16), 77 (10), 51 (16).
6-(1,2,4-Triazolo[1,5-a]pyrimidin-4-yl)-5-(1-pyrrolyl)-4-
methyl-2-phenylthieno[2,3-d]pyrimidine (26a)
This compound was synthesized from compound 1
(0.39 g, 1 mmol) and 3-amino-1,2,4-triazole 25a (0.10 g, 1
mmol) in a manner similar to that described for the prepara-
tion of 20a. It was recrystallized from ethanol/chloroform
to give 0.25 g of yellow crystals (62% yield), mp 217 °C;
1H NMR (CDCl3): d 2.38 (3H, s, CH3), 6.12 (1H, d, J = 1.0
Hz, 3-H of triazolopyrimidinyl), 6.56 (2H, m, 3,4-H of
pyrrolyl), 6.84 (2H, m, 2,5-H of pyrrolyl), 7.49 (1H, s, 7-H
of triazolopyrimidinyl), 8.54 (1H, d, J = 1.0 Hz, 2-H of tri-
azolopyrimidinyl), 8.63-8.61, 7.53-7.51 (5H, m, phenyl-
H); MS: 409 (M+, 100), 387 (76), 371 (30), 340 (28), 331
(18), 290 (38), 275 (6), 211 (6), 204 (12), 194 (11), 128 (4),
Anal. Calcd. for C38H25N7S: C, 74.63; H, 4.09; N,
16.04. Found: C, 74.33; H, 3.91; N, 16.11%.
6-(10-Methyl-8-phenyl-pyrimido[2,3:4,3]pyrazolo[1,5-
a]pyrimidin-4-yl)-5-(1-pyrrolyl)-4-methyl-2-phenyl-
thieno[2,3-d]pyrimidine (22c)
This compound was synthesized from compound 1
(0.39 g, 1 mmol) and 3-amino-4-methyl-6-phenyl-pyra-
zolo[3,4-d]pyrimidine 21c (0.23 g, 1 mmol) in a manner

Pyrrolylphenylthieno[2,3-d]pyrimidine Derivatives
J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 1085
Chem. Soc. 1989, 66, 48.
104 (11), 98 (31), 77 (13).
3. (a) Bousquet, E.; Romero, G.; Guerrera, F.; Caruso, A.;
Roxas, M. A. Farmaco Ed. Sci. 1985, 40, 869. (b) Bousquet,
E.; Guerrera, F.; Siracusa, N. A.; Caruso, A.; Roxas, M. A.
Farmaco Ed. Sci. 1984, 39, 110.
Anal. Calcd. for C22H15N7S: C, 64.54; H, 3.66; N,
23.96. Found: C, 64.42; H, 3.36; N, 24.21%.
6-(1,2,3,4-Tetrazolo[1,5-a]pyrimidin-4-yl)-5-(1-pyr-
rolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidine (26b)
This compound was synthesized from compound 1
(0.39 g, 1 mmol) and 5-amino-1H-tetrazole 25b (0.09 g, 1
mmol) in a manner similar to that described for the prepara-
tion of 20a. It was recrystallized from ethanol/chloroform
to give 0.25 g of pale yellow crystals (62% yield), mp 186
°C; MS: 410 (M+, 100).
4. Vieweg, H.; Leistner, S.; Wagner, G.; Boehm, N.; Krasset,
U.; Grupe, R.; Lohmann, D.; Loban, G., East German Patent
DD 1988, 257830.; Chem. Abstr. 1989, 110, 95262p.
5. (a) Chaykovsky, M.; Lin, M.; Rosowsky, A.; Modest, E. J. J.
Med. Chem. 1973, 10, 188. (b) Elsager, E. F.; Jacob, P.;
Werbel, L. M. J. Heterocycl. Chem. 1972, 9, 775.
6. Madding, G. D.; Thompson, M. D. J. Heterocycl. Chem.
1987, 24, 581.
7. Cheng, C. C. In Progress in Medicinal Chemistry; Vol 25,
Ellis, G. P.; West, G. B., Eds.; Elsevier Science Publisher B.
V. 1000 AE Amsterdam The Netherlands, 1989; p 35.
8. Shishoo, C. J.; Devani, M. B.; Bhadti, V. S. Indian Patent
1983, 151; Chem. Abstr. 1984, 100, 209858p.
Anal. Calcd. for C21H14N8S: C, 61.46; H, 3.41; N,
27.31. Found: C, 61.42; H, 3.36; N, 27.01%.
9. Ho, Y. W. J. Chin. Chem. Soc. 2001, 48, 1163.
10. Ho, Y. W.; Yao, C. T. J. Chin. Chem. Soc. 2003, 50, 283.
11. Ho, Y. W.; Yao, W. H. J. Chin. Chem. Soc. 2005, 52, 313.
12. Chauhan, S. M. S.; Junjappa, H. Synthesis 1975, 798.
13. Chauhan, S. M. S.; Junjappa, H. Tetrahedron 1976, 32, 1779.
14. Cheng, C. C.; Robins, R. K. J. Am. Chem. Soc. 1956, 78,
1240.
ACKNOWLEDGEMENT
We are grateful to the Nanya Institute of Technology
for financial support.
15. Taylor, E. C.; Hartke, K. S. J. Am. Chem. Soc. 1959, 81,
2452.
REFERENCES
16. El-Taweel, F. M. A.; Abu Elmaati, T. M. J. Chin. Chem. Soc.
2002, 49, 1051.
1. Brown, D. J.; Katritzky, A. R.; Rees, C. W. In Comprehen-
sive Heterocyclic Chemistry; Vol. 3, Boulton, A. J.;
McKillop, A., Eds.; 1984, p 57.
17. Dawood, Kamal M.; Farag, Ahmad M.; Ragab, Eman A. J.
Chin. Chem. Soc. 2004, 51, 853.
2. Dave, C. G.; Shah, P. R.; Dave, K. C.; Patel, V. J. J. Indian