Synthesis of novel pyrrylthieno-[2,3-d]pyrimidines and related pyrrolo[1″,2″:1′,6′]pyrazino-[2′,3′:4,5] thieno[2,3-d]pyrimidines

Article abstract of DOI:10.1080/10426500210243

4-Methyl-2-phenyl-5-(1-pyrryl)-6-substituted-thieno[2,3-d]pyrimidines (3a-c, 4a-c, 5a,b, and 6) have been synthesized. Some of the substituents in position 6 were used to build up different sulfur-, nitrogen-and/or oxygen-containing heterocyclic rings at that position. The 4-methyl- 2-phenyl-5-(1-pyrryl)-thieno[2,3-d]pyrimidine-6-carboazide (20) was also used as a key intermediate in the synthesis of the target pyrrolo[1″,2″:1′,6′]pyrazino[2′,3′:4, 5/thieno[2,3-d]pyrimidines.

Full text of DOI:10.1080/10426500210243

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Phosphorus, Sulfur, and Silicon and the Related
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Synthesis of Novel Pyrrylthieno[2,3-d]Pyrimidines and
Related
Pyrrolo[1″,2″:1″,6″]Pyrazino[2″,3″:4,5]Thieno[2,3-
d]Pyrimidines
E. A. Bakhite a , A. A. Geies a & H. S. El-Kashef a
a Chemistry Department, Faculty of Science , Assiut University , Assiut, 71516, Egypt
Published online: 27 Oct 2010.
To cite this article: E. A. Bakhite , A. A. Geies & H. S. El-Kashef (2002) Synthesis of Novel Pyrrylthieno[2,3-d]Pyrimidines and
Related Pyrrolo[1″,2″:1″,6″]Pyrazino[2″,3″:4,5]Thieno[2,3-d]Pyrimidines, Phosphorus, Sulfur, and Silicon and the Related
Elements, 177:2, 303-323, DOI: 10.1080/10426500210243
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Phosphorus, Sulfur and Silicon, 2002, 177:303–323
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Copyright 2002 Taylor & Francis
1042-6507/02 $12.00 + .00
SYNTHESIS OF NOVEL PYRRYLTHIENO-
[2,3-d]PYRIMIDINES AND RELATED
PYRROLO[100,200:10,60]PYRAZINO-
[20,30:4,5]THIENO[2,3-d]PYRIMIDINES
E. A. Bakhite, A. A. Geies, and H. S. El-Kashef
Chemistry Department, Faculty of Science, Assiut University,
Assiut 71516, Egypt
(Received February 7 2001.)
4-Methyl-2-phenyl-5-(1-pyrryl)-6-substituted-thieno[2,3-d]pyrimidines
(3a–c, 4a–c, 5a,b, and 6) have been synthesized. Some of the sub-
stituents in position 6 were used to build up different sulfur-, nitrogen-
and/or oxygen-containing heterocyclic rings at that position. The
4-methyl-2-phenyl-5-(1-pyrryl)-thieno[2,3-d]pyrimidine-6-carboazide
(20) was also used as a key intermediate in the synthesis of the target
pyrrolo[100,200:10,60]pyrazino[20,30:4,5]thieno[2,3-d]pyrimidines.
Keywords: Pyrrolopyrazinothienopyrimidines; pyrrylthienopyrimidi-
nes; thienopyrimidines
INTRODUCTION
Many thieno[2,3-d]pyrimidines have been investigated in relation
with their pharmacological activities. Some of them proved to pos-
sess antituberculosis,1 antianaphylactic,2 immunostimulating,3 anal-
gesic, and antiinflammatory4 activities. Others are useful as herps-
virus inhibitors5 and as endothelin antagonists.6 Very recently,7 certain
thieno[2,3-d]pyrimidine derivatives were prepared as immunosuppres-
sants for the treatment of reversible obstructive airway diseases such
as asthma, bronchitis, and rhinitis. In view of these observations and in
continuation to our program directed to the synthesis of new pyrazines
fused to aza- and diaza analogs of benzothiophene,8 10 we report herein
the synthesis of the hitherto unknown pyrrylthieno[2,3-d]pyrimidines
and related tetracyclic systems; pyrrolopyrazinothienopyrimidines.
Address correspondence to H. S. El-Kashef, Chemistry Department, Faculty of
Science, Assiut University, Assiut 71516, Egypt.
303

304
E. A. Bakhite et al.
RESULTS AND DISCUSSION
5-Cyano-6-methyl-2-phenylpyrimidine-4(3H)-thione (1)11 was reacted
with some halo compounds, viz chloroacetone, phenacyl bromide,
or ethyl chloroacetate, by refluxing in ethanol containing anhy-
drous potassium carbonate, to give the corresponding 5-amino-
4-methyl-2-phenyl-6-substituted-thieno[2,3-d]pyrimidines (2a–c). The
amino group of the latter compounds was easily transformed into
a pyrryl moiety via the reaction with 2,5-dimethoxytetrahydrofuran
in boiling acetic acid12,13 to give the pyrryl derivatives 3a–c.
The acetyl compound 3a was easily converted into the chal-
cones 4a–c, phenylhydrazone 5a, and also into thiosemicarbazone
5b upon treatment with aromatic aldehydes, phenylhydrazine, or
thiosemicarbazide respectively. Treatment of the ester 3c with hy-
drazine hydrate resulted in the formation of 4-methyl-2-phenyl-
5-(1-pyrryl)-thieno[2,3-d]pyrimidine-6-carbohydrazide (6) (Scheme 1).
SCHEME 1

Synthesis of Novel Pyrrylthieno[2,3-d]pyrimidines
305
The compounds 4a–c, 5b, and 6 served as useful intermediates for
the synthesis of pyrrylthienopyrimidines containing different hetero-
cyclic residues at position 6. Thus, when the chalcones 4a–c were
interacted with hydrazine hydrate or phenylhydrazine, the products
were identified as pyrazolinyl derivatives 7a–c and 8a–c respec-
tively. However, their reaction with hydroxylamine led to the for-
mation of isoxazolinyl derivatives 9a–c. On the other hand, the in-
teraction of 4a–c with thiourea in boiling ethanol in the presence
of catalytic amounts of HCl produced the pyrimidinethiones 10a–c
(Scheme 2).
SCHEME 2
The thiosemicarbazone 5b was reacted with phenacyl bro-
mide, p-chlorophenacyl bromide, ethyl chloroacetate, or methyl
2-bromopropionate by refluxing in ethanol containing fused sodium

306
E. A. Bakhite et al.
SCHEME 3
acetate to furnish the thiazolines 11a,b and thiazolidinones 12a,b re-
spectively (Scheme 3).
The condensation of carbohydrazide 6 with some aromatic alde-
hydes yielded the expected hydrazones 13a–c. On treatment of 13a
with acetic anhydride at reflux temperature, the acetyloxadiazolinyl
derivative 14 was isolated. The pyrazolyl derivative 15 was obtained
upon fusion of 6 with acetylacetone. Compound 6 was also reacted
with phenyl isothiocyanate to afford the thiosemicarbazide 16 which
was cyclized into s-triazole derivative 17 upon heating in aqueous
sodium hydroxide solution. The 1,3,4-oxadiazole-5(4H)-thione 18 was
prepared by reacting 6 with carbon disulfide in the presence of potas-
sium hydroxide. When the thiones 17 and 18 were allowed to react
with ethyl chloroacetate, the corresponding esters 19a,b were obtained
(Scheme 4).
The treatment of a solution of 6 in glacial acetic acid with sodium ni-
trite solution at low temperature resulted in the formation of 4-methyl-
2-phenyl-5-(1-pyrryl)-thieno[2,3-d]pyrimidine-6-carboazide (20). This
azide served as a point of departure into other pyrrylthienopyrim-
idines and also it was used as a key intermediate in the synthesis
of new tetracyclic heterocycles, pyrrolopyrazinothienopyrimidines.
Thus, when 20 was heated in alcohols, Curtius rearrangement oc-
curred and the formed isocyanate 21 reacted concomitantly with al-
cohols used to give the corresponding N-alkyl carbamates 22a,b.
Similarly, fusion of 20 with different amines led to the forma-
tion of the urea derivatives 23a–f. However, when the acid azide
20 was heated in an inert high boiling point solvent such as dry
xylene and in absence of any reactive entity, Curtius rearrangement

Synthesis of Novel Pyrrylthieno[2,3-d]pyrimidines
307
SCHEME 4
took place with subsequent intramolecular ring closure to give
the 4-methyl-2-phenylpyrrolo[100,200:10,60]pyrazino[20,30:4,5]thieno[2,3-
d]pyrimidine-9(10H)-one (24) (Scheme 5).
The pyrazinethione 25 was obtained by heating 24 with phospho-
rus pentasulfide in dry pyridine. This thione was easily reacted with
p-chlorophenacyl bromide or ethyl chloroacetate to furnish pyrrolopy-
razinothienopyrimidines 26a,b. It is worthy to mention that when
26b was treated with hydrazine hydrate in ethanol at room tem-
perature, the product was the acethydrazide 27, however, when the
reaction was carried out by fusion of the two reactants, the hy-
drazino derivative 29 was obtained. The latter compound was ob-
tained unequivocally by chlorinating 24 followed by nucleophilic

308
E. A. Bakhite et al.
SCHEME 5
displacement of the labile chlorine with hydrazine hydrate. The com-
pound 29 underwent some cyclization reactions upon treatment with
triethyl orthoformate, acetic acid and/or carbon disulfide to give
s-triazolo[4000,3000:40,50]pyrrolo[100,200 :10,60]pyrazino[20,30:4,5]thieno[2,3-d]
pyrimidine derivatives 30a–c (Scheme 6).
Elemental analyses and spectroscopic data of all compounds pre-
pared are shown in Tables I and II respectively.
EXPERIMENTAL
All melting points are uncorrected and measured on a Fisher-
John apparatus. IR spectra were recorded on a Shimadzu 470 IR-
1
Spectrophotometer (KBr;
in cm 1); H-NMR spectra on a Varian
max
EM-390, 90 MHz spectrometer with TMS as an internal standard ( in
ppm). Elemental analyses (C, H, N) were carried out on a Perkin-Elmer
240C elemental analyser. Sulfur and chlorine analyses were obtained

Synthesis of Novel Pyrrylthieno[2,3-d]pyrimidines
309
SCHEME 6
using oxygen flask method by the microanalytical Unite at Assiut
University.
5-Cyano-6-methyl-2-phenylpyrimidine-4(3H)-thione (1)
It was prepared by the reported method.15
Reaction of Compound 1 with Chloroacetone, Phenacyl
Bromide or Ethyl Chloroacetate; Formation
of Thieno[2,3-d]pyrimidines 2a--c
To a suspension of 1 (4.54 g, 0.02 mol) and anhydrous potassium
carbonate (8.28 g, 0.06 mol) in ethanol (80 mL), the respective halo

310
E. A. Bakhite et al.
TABLE I Physical Properties and Analytical Data (Calc./Found %) of the
Prepared Compounds
Sol. of cryst.
color
m.p. ( C)
yield (%)
Mol. formula
(M.Wt.)
Comp.
C
H
N
S
2a
Ethanol
Yellow
Ethanol
Yellow
Ethanol
Yellow
Ethanol
White
Ethanol
White
Ethanol
White
Dioxane
Yellow
Dioxane
Yellow
Dioxane
Red
Acetic acid
Yellow
Acetic acid
Yellow
Ethanol
White
Ethanol
Pale yellow
Ethanol
Pale yellow
Ethanol
Pale yellow
Dioxane
Yellow
Dioxane
Yellow
Dioxane
Red
221–222
77
235–238
86
175–176
80
186–187
76
163–164
79
175–176
81
182–184
65
238–239
71
176–177
70
>300
90
243–244
83
220–221
79
205–206
80
221–222
73
254–255
76
179–180
82
260–261
81
274–275
86
173–174
69
170–171
66
158–159
65
197–198
65
220–221
70
C15H13N3OS
283.4
C20H15N3OS
345.4
C16H15N3O2S
313.37
63.58
63.19
69.54
69.35
61.32
61.49
68.45
68.66
72.89
72.97
66.10
66.33
74.09
73.80
71.82
71.77
72.39
72.28
70.90
70.69
59.09
58.92
61.88
62.02
71.70
71.83
69.66
69.50
70.27
70.19
75.12
75.28
73.17
73.10
73.62
73.89
71.54
71.64
69.51
69.52
70.12
70.03
67.62
67.38
65.99
66.17
4.62
4.79
4.38
4.42
4.82
4.76
4.53
4.50
4.33
4.37
4.71
4.43
4.54
4.56
4.69
4.59
5.21
5.25
5.00
5.11
4.46
4.37
4.33
4.45
4.86
4.70
4.98
5.16
5.48
5.63
4.93
5.05
5.02
5.26
5.45
5.62
4.62
4.67
4.75
4.62
5.25
5.44
4.41
4.56
4.55
4.42
14.83
14.62
12.16
12.00
13.41
13.52
12.60
12.39
10.63
10.86
11.56
11.50
9.97
11.31
11.50
9.28
9.43
10.23
10.00
9.62
9.91
8.11
8.03
8.82
9.09
7.61
7.52
7.10
7.34
6.90
6.75
7.57
7.40
15.77
16.00
9.18
9.32
7.36
7.19
6.89
6.70
6.70
6.93
6.27
6.04
5.92
5.81
5.78
5.57
7.34
7.61
6.87
7.11
6.68
6.79
13.37
13.21
12.56
12.69
2b
2ca
3a
3b
3c
C
19H15N3OS
333.41
C24H17N3OS
395.5
C
20H17N3O2S
363.4
4a
4b
4c
C
26H19N3OS
421.5
10.17
9.31
9.53
C27H21N3O2S
451.5
C
28H24N4OS
464.6
12.06
12.11
16.54
16.48
20.67
20.51
20.04
19.77
16.08
16.25
15.04
14.93
17.56
17.72
13.69
13.55
12.93
12.87
15.15
15.00
12.83
12.71
12.01
11.95
14.60
14.87
14.60
14.70
13.75
13.67
5a
5b
6
C25H21N5S
423.5
C
20H18N6S2
406.5
C18H15N5OS
349.4
C26H21N5S
435.6
7a
7b
7c
C
27H23N5OS
465.6
C28H26N6S
478.6
8a
8b
8c
C
32H25N5S
511.6
C33H27N5OS
541.7
C
34H30N6S
554.7
9a
9b
9c
Ethanol
Pale yellow
Ethanol
Pale yellow
Ethanol
Yellow
Acetic acid
Yellow
Acetic acid
Yellow
C
26H20N4OS
436.5
C
27H22N4O2S
466.6
C
28H25N5OS
479.6
10a
10b
C27H21N5S2
479.6
C28H23N5OS2
509.64

Synthesis of Novel Pyrrylthieno[2,3-d]pyrimidines
311
TABLE I Physical Properties and Analytical Data (Calc./Found %) of the
Prepared Compounds (Continued)
Sol. of Cryst.
Color
m.p. ( C)
Yield (%)
Mol. formula
(M. Wt.)
Comp.
C
H
N
S
10c
Acetic acid
Yellow
Dioxane
Yellow
Dioxane
Yellow
Dioxane
White
Dioxane
White
Ethanol
White
Ethanol
White
Ethanol
Yellow
Ethanol
White
Ethanol
White
Dioxane
White
Ethanol
White
Ethanol
White
Methanol
White
Methanol
White
Not cryst.
White
182–184
67
211–212
83
234–235
85
235–236
89
242–243
84
259–261
88
295–296
87
297–298
91
218–219
72
170–171
76
289–291
90
286–287
75
293–294
83
210–211
87
192–193
84
163–165
75
C29H26N6S2
522.7
C28H22N6S2
506.6
C28H21ClN6S2
541.1
66.64
66.90
66.38
66.41
62.15
62.28
59.17
60.11
59.98
59.83
68.63
67.88
66.79
66.83
67.48
67.44
67.62
67.75
66.81
67.12
61.96
62.17
64.36
64.20
58.30
58.33
63.02
62.81
57.85
57.50
59.99
60.17
63.47
63.40
64.27
64.20
61.05
60.86
67.75
67.94
68.32
68.34
68.32
68.63
5.01
5.17
4.38
4.26
3.91
3.04
4.06
4.09
4.38
4.54
4.38
4.26
4.53
4.76
5.03
5.11
4.41
4.47
4.63
4.56
4.16
4.15
3.89
3.73
3.35
3.42
4.38
4.56
4.01
4.09
3.36
3.56
4.79
4.65
5.14
5.00
4.87
4.67
4.50
4.47
4.82
4.65
4.82
4.78
16.08
15.97
16.59
16.72
15.53
15.31
18.82
18.96
18.25
18.37
16.01
16.17
14.99
15.27
17.49
17.65
14.60
14.54
16.94
16.75
17.34
17.65
18.01
18.22
17.89
17.98
15.21
15.43
14.66
14.41
23.32
23.19
14.80
14.73
14.28
14.43
17.80
17.95
16.46
16.81
15.93
15.71
15.93
16.09
12.27
12.34
12.66
12.59
11.85
12.00
14.36
14.60
13.92
14.15
7.33
7.51
6.84
7.15
6.67
7.02
6.69
6.84
7.75
11a
11bb
12a
12b
13a
13b
13c
14
C
22H18N6OS2
446.5
C23H20N6OS2
460.6
C
25H19N5OS
437.5
C
26H21N5O2S
467.6
C27H24N6OS
480.6
C
27H21N5O2S
479.6
15
C23H19N5OS
413.5
7.63
16
C
25H20N6OS2
484.6
13.23
13.07
13.74
13.67
16.38
16.21
11.60
11.77
13.43
13.48
8.90
8.77
8.47
8.69
8.17
8.32
8.15
8.34
7.53
17
C
25H18N6S2
466.6
18
C19H13N5OS2
391.5
19a
19b
20
C
29H24N6O2S2
552.7
C23H19N5O3S2
477.6
C
18H12N6OS
360.4
22a
22b
23a
23b
23c
23d
Ethanol
White
Iso-propanol
White
Methanol
White
Ethanol
White
Ethanol
White
Ethanol
White
245–246
67
251–252
78
235–236
90
>300
81
>300
82
>300
80
C20H18N4O2S
378.5
C
21H20N4O2S
392.5
C
20H19N5O2S
393.5
C24H19N5OS
425.5
7.50
7.29
7.16
7.29
C25H21N5OS
439.5
C25H21N5OS
439.5
7.45
(Continued on next page)

312
E. A. Bakhite et al.
TABLE I Physical Properties and Analytical Data (Calc./Found %) of the
Prepared Compounds (Continued)
Sol. of cryst.
color
m.p. ( C)
yield (%)
Mol. formula
(M.Wt.)
Comp.
C
H
N
S
23e
Dioxane
White
Dioxane
White
DMF
Pale yellow
DMF
>300
79
>300
81
>300
65
>300
66
159–160
81
150–151
74
271–272
63
287–288
81
>300
71
275–276
80
271–272
69
293–294
70
C25H21N5O2S
455.5
C24H18ClN5OS
460.0
C18H12N4OS
332.4
65.92
65.71
62.67
62.90
65.05
65.17
62.05
62.29
62.33
62.14
60.81
60.75
57.13
57.42
61.63
61.76
62.41
62.29
64.03
64.25
64.85
64.72
58.75
58.82
4.65
4.72
3.94
4.15
3.64
3.51
3.47
3.39
3.42
3.68
4.18
4.53
3.84
3.80
3.16
3.22
4.07
4.15
3.39
3.36
3.81
3.71
3.11
3.27
15.37
15.51
15.23
15.00
16.86
16.69
16.08
16.30
11.18
11.05
12.89
12.66
19.99
19.87
15.97
16.06
24.26
24.45
23.58
23.70
22.69
22.93
21.63
21.51
7.04
7.32
6.97
7.18
9.65
23fc
24
9.53
25
C18H12N4S2
18.40
18.56
12.80
13.10
14.76
14.95
15.25
15.31
9.14
9.10
9.25
9.18
9.00
Yellow
348.4
C26H17ClN4OS2
501.0
26ad
26b
27
Dioxane
Pale yellow
Ethanol
Pale yellow
Dioxane
Pale yellow
Chloroform
Pale yellow
Dioxane
Yellow
Dioxane
Pale yellow
Dioxane
Pale yellow
Acetic acid
Yellow
C22H18N4O2S2
434.5
C20H16N6OS2
420.5
C18H11ClN4S
350.8
28e
29
C
18H14N6S
346.4
30a
30b
30c
C19H12N6S
356.4
9.18
8.65
8.69
16.51
16.79
C
20H14N6S
370.4
C19H12N6S2
388.5
aLit.11 m.p. 174–176 C.
bCalcd. Cl = 6.55%; Found = 6.40%.
cCalcd. Cl = 7.71%; Found = 7.90%.
dCalcd. Cl = 7.08%; Found = 6.93%.
eCalcd. Cl = 10.11%; Found = 10.32%.
compound (0.02 mol) was added. The resulting mixture was heated
under reflux for 3 h and then left to cool. The precipitate that formed
was filtered off, washed thoroughly with water, and recrystallized to
give 2a–c.
Reaction of Compounds 2a--c with 2,5-
Dimethoxytetrahydrofuran; Formation
of Pyrrylthieno[2,3-d]pyrimidines 3a--c
A mixture of 2a–c (0.02 mol) and 2,5-dimethoxytetrahydrofuran
(2.6 mL, 0.02 mol) in glacial acetic acid (40 mL) was heated under reflux
for 1 h. The solid product was collected and recrystallized to give 3a–c.

Synthesis of Novel Pyrrylthieno[2,3-d]pyrimidines
313
TABLE II IR and 1H NMR Spectral Data of the Prepared Compounds
1
Compd.
IR [cm
]
1H NMR [ppm]
2a
3470, 3300
(NH2); 1630
(C O)
(CDCl3): 8.0–8.2 (m, 2H, ArH’s); 7.2–7.5 (m, 3H, ArH’s);
6.3–6.7 (br, 2H, NH2); 2.5 (s, 3H,CH3); 2.3 (s, 3H, CH3)
2b
2c
3a
3b
3c
4a
4b
4c
5a
5b
3470, 3300
(NH2); 1630
(C O)
3480, 3300
(NH2); 1660
(C O)
(CDCl3): 8.1–8.4 (m, 2H, ArH’s); 7.0–7.6 (m, 8H, ArH’s);
6.4–6.7 (br, 2H, NH2); 2.4 (s, 3H, CH3)
(CDCl3): 8.1–8.3 (m, 2H, ArH’s); 7.2–7.5 (m, 3H, ArH’s);
5.6 (s, 2H, NH2); 4.3 (q, 2H, OCH2); 2.6 (s, 3H, CH3);
1.3 (t, 3H, CH3)
(CDCl3): 8.1–8.3 (m, 2H, ArH’s); 7.2–7.5 (m, 3H, ArH’s);
6.8 (m, 2H, 2CH pyrrole); 6.4 (m, 2H, 2CH pyrrole);
2.8 (s, 3H, CH3); 2.5 (s, 3H, CH3)
(CDCl3): 8.2–8.5 (m, 2H, ArH’s); 7.0–7.7 (m, 8H, ArH’s);
6.6 (m, 2H, 2CH pyrrole); 6.3 (m, 2H, 2CH pyrrole);
2.4 (s, 3H, CH3)
(CDCl3): 8.0–8.2 (m, 2H, ArH’s); 7.3–7.6 (m, 3H, ArH’s);
6.7 (m, 2H, 2CH pyrrole); 6.4 (m, 2H, 2CH pyrrole);
4.3 (q, 2H, OCH2); 2.5 (s, 3H, CH3); 1.2 (t, 3H, CH3)
(DMSO-d6): 7.0–8.2 (m, 12H, ArH’s, CH CH);
6.8 (m, 2H, 2CH pyrrole); 6.3 (m, 2H, 2CH pyrrole);
2.6 (s, 3H, CH3)
(DMSO-d6): 6.7–8.2 (m, 11H, ArH’s, CH CH);
6.8 (m, 2H, 2CH pyrrole); 6.4 (m, 2H, 2CH pyrrole);
3.9 (s, 3H, OCH3); 2.5 (s, 3H, CH3)
(DMSO-d6): 6.8–8.3 (m, 11H, ArH’s, CH CH);
6.8 (m, 2H, 2CH pyrrole); 6.4 (m, 2H, 2CH pyrrole);
3.0 (s, 6H, N(CH3)2); 2.5 (s, 3H, CH3)
(DMSO-d6): 9.8 (s, 1H, NH); 6.9–8.3 (m, 10H, ArH’s);
6.8 (m, 2H, 2CH pyrrole); 6.5 (m, 2H, 2CH pyrrole);
2.4 (s, 3H, CH3); 2.1 (s, 3H, CH3)
(DMSO-d6): 10.3 (s, 1H, NH); 8.4 (s, 2H, NH2); 8.0–8.2
(m, 2H, ArH’s); 7.5–7.7 (m, 3H, ArH’s); 6.7 (m, 2H,
2CH pyrrole); 6.4 (m, 2H, 2CH pyrrole); 2.5 (s, 3H,
CH3); 2.0 (s, 3H, CH3)
1680 (C O)
1650 (C O)
1680 (C O)
1650 (C O);
1590 (C C)
1650 (C O);
1590 (C C)
1650 (C O);
1590 (C C)
3370 (NH)
3400-3130
(NH2, NH);
1230 (C S)
6
3450-3120
(NHNH2);
1640 (C O)
3200 (NH);
1600 (C N)
(CDCl3): 9.6 (s, 1H, NH); 8.1–8.3 (m, 2H, ArH’s); 7.2–7.5
(m, 3H, ArH’s); 6.8 (m, 2H, 2CH pyrrole); 6.4 (m, 2H,
2CH pyrrole); 4.5 (s, 2H, NH2); 2.5 (s, 3H, CH3)
(CDCl3): 7.0–8.2 (m, 10H, ArH’s); 6.8 (m, 2H, 2CH
pyrrole); 6.4 (m, 2H, 2CH pyrrole); 4.7 (t, 1H, CH
pyrazoline); 3.3 (m, 2H, CH2 pyrazoline); 2.9 (s, 1H,
NH) and 2.6 (s, 3H, CH3)
7a
7b
3240 (NH);
1600 (C N)
(CDCl3): 6.8–8.3 (m, 9H, ArH’s); 6.8 (m, 2H, 2CH pyrrole);
6.4 (m, 2H, 2CH pyrrole); 4.7 (t, 1H, CH pyrazoline);
3.9 (s, 3H, OCH3); 3.3 (m, 2H, CH2 pyrazoline);
2.9 (s,1H, NH); 2.6 (s, 3H, CH3)
(Continued on next page)

314
E. A. Bakhite et al.
TABLE II IR and 1H NMR Spectral Data of the Prepared Compounds
(Continued)
1
Compd.
IR [cm
]
1H NMR [ppm]
7c
3200 (NH);
(CDCl3): 6.8–8.3 (m, 9H, ArH’s); 6.8 (m, 2H, 2CH pyrrole);
6.4 (m, 2H, 2CH pyrrole); 4.7 (t, 1H, CH pyrazoline);
3.0 (s, 6H, N (CH3)2); 3.3 (m, 2H, CH2 pyrazoline);
2.9 (s,1H, NH); 2.6 (s, 3H, CH3)
(DMSO-d6): 6.9–8.3 (m,15H, ArH’s); 6.8 (m, 2H, 2CH pyrrole);
6.4 (m, 2H, 2CH pyrrole); 4.7 (t, 1H, CH pyrazoline);
3.3 (m, 2H, CH2 pyrazoline); 2.6 (s, 3H, CH3)
(DMSO-d6): 6.7–8.3 (m,14H, ArH’s); 6.7 (m, 2H, 2CH pyrrole);
6.4 (m, 2H, 2CH pyrrole); 4.7 (t, 1H, CH pyrazoline);
3.8 (s, 3H, OCH3); 3.3 (m, 2H, CH2 pyrazoline);
2.6 (s, 3H, CH3)
1600 (C N)
1620 (C N)
1610 (C N)
8a
8b
8c
1620 (C N)
(CDCl3): 6.6–8.2 (m, 14H, ArH’s); 6.7 (m, 2H, 2CH pyrrole);
6.3 (m, 2H, 2CH pyrrole); 4.7 (t, 1H, CH pyrazoline);
3.1 (s, 6H, N(CH3)2); 3.3 (m, 2H, CH2 pyrazoline);
2.6 (s, 3H, CH3)
9a
9b
1600 (C N)
1600 (C N)
(CDCl3): 6.9–8.2 (m,10H, ArH’s); 6.8 (m, 2H, 2CH pyrrole);
6.4 (m, 2H, 2CH pyrrole); 4.6 (t, 1H, CH isoxazoline);
3.2 (m, 2H, CH2 isoxazoline); 2.7 (s, 3H, CH3)
(CDCl3): 6.6–8.3 (m, 9H, ArH’s); 6.7 (m, 2H, 2CH pyrrole);
6.4 (m, 2H, 2CH pyrrole); 4.8 (t, 1H, CH isoxazoline);
3.8 (s, 3H, OCH3); 3.3 (m, 2H, CH2 isoxazoline);
2.6 (s, 3H, CH3)
9c
1610 (C N)
(CDCl3): 6.7–8.2 (m, 9H, ArH’s); 6.8 (m, 2H, 2CH pyrrole);
6.5 (m, 2H, 2CH pyrrole); 4.7 (t, 1H, CH isoxazoline);
3.1 (s, 6H, N(CH3)2); 3.4 (m, 2H, CH2 isoxazoline);
2.7 (s, 3H, CH3)
10a
10b
10c
3180 (NH);
1640 (NCS)
(DMSO-d6): 9.8 (s, 1H, NH); 9.2 (s, 1H, NH); 6.9–8.2 (m, 10H,
ArH’s); 6.8 (m, 2H, 2CH pyrrole); 6.4 (m, 2H, 2CH pyrrole);
5.3 (m, 1H, CH pyrimidine); 4.5 (d, 1H, CH pyrimidine); 2.7
(s, 3H, CH3)
(DMSO-d6): 9.9 (s, 1H, NH); 9.3 (s, 1H, NH); 6.8–8.3 (m, 9H,
ArH’s); 6.7 (m, 2H, 2CH pyrrole); 6.4 (m, 2H, 2CH pyrrole);
5.4 (m, 1H, CH pyrimidine); 4.6 (d, 1H, CH pyrimidine);
3.8 (s, 3H, OCH3); 2.6 (s, 3H, CH3)
(CDCl3): 9.6 (s, 1H, NH); 9.3 (s, 1H, NH); 7.0–8.3 (m, 9H,
ArH’s); 6.8 (m, 2H, 2CH pyrrole); 6.5 (m, 2H, 2CH pyrrole);
5.4 (m, 1H, CH pyrimidine); 4.6 (d, 1H, CH pyrimidine); 3.0
(s, 6H, N(CH3)2); 2.7 (s, 3H, CH3)
3180 (NH);
1640 (NCS)
3180 (NH);
1640 (NCS)
11a
11b
3420 (NH)
3420 (NH)
(TFA): 6.9–8.2 (m,11H, ArH’s, CH thiazoline); 6.8 (m, 2H, 2CH
pyrrole); 6.4 (m, 2H, 2CH pyrrole); 2.6 (s, 3H, CH3);
2.1 (s, 3H, CH3)
(TFA): 6.9–8.4 (m, 10H, ArH’s, CH thiazoline); 6.7 (m, 2H,
2CH pyrrole); 6.4 (m, 2H, 2CH pyrrole); 2.6 (s, 3H, CH3);
2.2 (s, 3H, CH3)

Synthesis of Novel Pyrrylthieno[2,3-d]pyrimidines
315
TABLE II IR and 1H NMR Spectral Data of the Prepared Compounds
(Continued)
1
Compd.
IR [cm
]
1H NMR [PPM]
12a
3100 (NH);
1710 (C O)
(TFA): 8.0–8.3 (m, 2H, ArH’s); 7.5–7.8 (m, 3H, ArH’s);
6.8 (m, 2H, 2CH pyrrole); 6.5 (m, 2H, 2CH pyrrole);
4.1 (s, 2H, CH2 thiazolidinone); 2.5 (s, 3H, CH3);
2.0 (s, 3H, CH3)
12b
3100 (NH);
1710 (C O)
(TFA): 8.1–8.3 (m, 2H, ArH’s); 7.5–7.8 (m, 3H, ArH’s);
6.8 (m, 2H, 2CH pyrrole); 6.4 (m, 2H, 2CH pyrrole);
4.0 (q, 1H, CH thiazolidinone); 2.6 (s, 3H, CH3);
2.1 (s, 3H, CH3); 1.7 (d, 3H, CH3)
13a
13b
3300 (NH);
1680 (C O)
3300 (NH);
1680 (C O)
(TFA): 6.9–8.3 (m, 11H, ArH’s, and N CH); 6.6 (m, 2H, 2CH
pyrrole); 6.3 (m, 2H, 2CH pyrrole); 2.6 (s, 3H, CH3)
(TFA): 6.8–8.3 (m, 10H, ArH’s, and N CH); 6.6 (m, 2H, 2CH
pyrrole); 6.3 (m, 2H, 2CH pyrrole); 3.3 (s, 3H, OCH3); 2.6
(s, 3H, CH3)
13c
14
3300 (NH);
1680 (C O)
(TFA): 6.8–8.3 (m, 10H, ArH’s, and N CH); 6.6 (m, 2H, 2CH
pyrrole); 6.3 (m, 2H, 2CH pyrrole); 3.8 (s, 6H, N(CH3)2);
2.6 (s, 3H, CH3)
(CDCl3): 6.9–8.3 (m, 10H, ArH’s); 6.7 (m, 2H, 2CH pyrrole);
6.3 (m, 2H, 2CH pyrrole); 3.0 (s, 1H, CH oxadiazoline);
2.6 (s, 3H, CH3); 2.3 (s, 3H, CH3CO)
(CDCl3): 8.0–8.3 (m, 2H, ArH’s); 7.1–7.4 (m, 3H, ArH’s);
6.6 (m, 2H, 2CH pyrrole); 6.4 (m, 2H, 2CH pyrrole);
6.1 (s, 1H, CH pyrazole); 2.7, 2.5,2.3 (3s, 9H, 3XCH3)
(DMSO-d6): 9.8 (s, 1H, NH); 9.6 (s, 1H, NH); 7.0–8.2 (m,
11H, ArH’s and NH); 6.8 (m, 2H, 2CH pyrrole);
6.4 (m, 2H, 2CH pyrrole); 2.7 (s, 3H, CH3)
(DMSO-d6): 13.3 (s, 1H, NH); 7.0–8.2 (m, 10H, ArH’s);
6.8 (m, 2H, 2CH pyrrole); 6.4 (m, 2H, 2CH pyrrole);
2.7 (s, 3H, CH3)
1650 (C O)
1660 (C O)
15
16
3350–3160
(NH);
1650(C O)
3100 (NH);
1600 (C N)
17
18
3300 (NH);
1600 (C N)
(CDCl3):13.0 (s, 1H, NH); 8.0–8.3 (m, 2H, ArH’s); 7.1–7.4 (m,
3H, ArH’s); 6.8 (m, 2H, 2CH pyrrole); 6.4 (m, 2H, 2CH
pyrrole); 2.7 (s, 3H, CH3)
19a
19b
1720 (C O)
1720 (C O)
(CDCl3):7.1–8.3 (m, 10H, ArH’s); 6.8 (m, 2H, 2CH pyrrole);
6.5 (m, 2H, 2CH pyrrole); 4.3 (q, 2H, OCH2); 3.9 (s, 2H,
SCH2); 2.7 (s, 3H, CH3); 1.2 (t, 3H, CH3)
(CDCl3): 8.0–8.3 (m, 2H, ArH’s); 7.1-7.4 (m, 3H, ArH’s);
6.8 (m, 2H, 2CH pyrrole); 6.5 (m, 2H, 2CH pyrrole);
4.4 (q, 2H, OCH2); 4.1 (s, 2H, SCH2); 2.7 (s, 3H, CH3);
1.3 (t, 3H, CH3)
20
3150 (N3);
1660 (C O)
(CDCl3): 8.1–8.3 (m, 2H, ArH’s); 7.1–7.4 (m, 3H, ArH’s);
6.8 (m, 2H, 2CH pyrrole); 6.5 (m, 2H, 2CH pyrrole);
2.6 (s, 3H, CH3)
22a
3400 (NH);
1720 (C O)
(TFA): 8.1–8.3 (m, 2H, ArH’s); 7.4–7.7 (m, 3H, ArH’s);
6.8 (m, 2H, 2CH pyrrole); 6.5 (m, 2H, 2CH pyrrole);
4.3 (q, 2H, OCH2); 2.5 (s, 3H, CH3); 1.3 (t, 3H, CH3)
(Continued on next page)

316
E. A. Bakhite et al.
TABLE II IR and 1H NMR Spectral Data of the Prepared Compounds
(Continued)
1
Compd.
IR [cm
]
1H NMR [ppm]
22b
3400 (NH);
1720 (C O)
(TFA): 8.0–8.3 (m, 2H, ArH’s); 7.5–7.8 (m, 3H, ArH’s);
6.9 (m, 2H, 2CH pyrrole); 6.5 (m, 2H, 2CH pyrrole);
5.5 (m, 1H, OCH); 2.4 (s, 3H, CH3); 1.6 (d, 6H, 2XCH3)
(CDCl3): 8.5 (s, 1H, NH); 8.0–8.3 (m, 3H, ArH’s NH);
7.2–7.5 (m, 3H, ArH’s); 6.8 (m, 2H, 2CH pyrrole);
6.5 (m, 2H, 2CH pyrrole); 3.2–3.8 (m, 5H, (CH2)2
and OH); 2.4 (s, 3H, CH3)
23a
3500–3100
(OH, NH);
1630 (C O)
23b
23c
23d
23e
23f
24
3400–3100
(NH);
1640 (C O)
3400–3100
(NH);
1640 (C O)
3400–3100
(NH);
1640 (C O)
3400–3100
(NH);
1640 (C O)
3400–3100
(NH);
1650 (C O)
3200–2400
(NH);
1640 (C O)
3400–3200
(NH);
1250 (C S)
1680 (C O);
1600 (C N)
(DMSO-d6): 9.7 (s, 1H, NH); 8.9 (s,1H, NH); 6.8–8.3 (m,
10H, ArH’s); 6.8 (m, 2H, 2CH pyrrole); 6.4 (m, 2H,
2CH pyrrole); 2.4 (s, 3H, CH3)
(DMSO-d6): 9.7 (s, 1H, NH); 8.8 (s,1H, NH); 6.9–8.3 (m, 9H,
ArH’s); 6.8 (m, 2H, 2CH pyrrole); 6.4 (m, 2H,
2CH pyrrole); 2.5 (s, 3H, CH3); 2.3 (s, 3H, CH3)
(DMSO-d6): 9.8 (s,1H, NH); 9.0 (s,1H, NH); 6.9–8.3 (m, 9H,
ArH’s); 6.8 (m, 2H, 2CH pyrrole); 6.4 (m, 2H,
2CH pyrrole); 2.5 (s, 3H, CH3); 2.2 (s, 3H, CH3)
(DMSO-d6): 9.8 (s,1H, NH); 8.9 (s,1H, NH); 6.9–8.3 (m, 9H,
ArH’s); 6.7 (m, 2H, 2CH pyrrole); 6.4 (m, 2H,
2CH pyrrole); 3.8 (s, 3H, OCH3); 2.5 (s, 3H, CH3)
(DMSO-d6): 9.7 (s, 1H, NH); 8.9 (s,1H, NH); 6.8–8.3 (m, 9H,
ArH’s); 6.8 (m, 2H, 2CH pyrrole); 6.4 (m, 2H,
2CH pyrrole); 2.4 (s, 3H, CH3)
(TFA): 8.0–8.4 (m, 3H, ArH’s and CH pyrrole); 7.6 (d, 1H,
CH pyrrole); 7.0–7.3 (m, 3H, ArH’s); 6.9 (m, 1H,
CH pyrrole); 2.9 (s, 3H, CH3)
(TFA): 8.1–8.3 (m, 3H, ArH’s, CH pyrrole); 7.5 (d, 1H, CH
pyrrole); 7.0–7.3 (m, 3H, ArH’s); 6.9 (m, 1H, CH pyrrole);
2.8 (s, 3H, CH3)
25
26a
26b
(DMSO-d6): 8.0–8.4 (m, 3H, ArH’s, CH pyrrole); 7.6 (d, 1H,
CH pyrrole); 7.0–7.3 (m, 7H, ArH’s); 6.9 (m, 1H, CH
pyrrole); 5.4 (s, 2H, SCH2); 2.9 (s, 3H, CH3)
(DMSO-d6): 8.0–8.4 (m, 3H, ArH’s, CH pyrrole); 7.6 (d, 1H,
CH pyrrole); 7.0–7.3 (m, 3H, ArH’s); 6.9 (m, 1H, CH
pyrrole); 4.2–4.5 (q, 2H, OCH2); 4.0 (s, 2H, SCH2); 2.9
(s, 3H, CH3); 1.1–1.4 (t, 3H, CH3)
1730 (C O);
1600 (C N)
30a
30b
30c
1600 (C N)
1600 (C N)
(TFA): 9.4 (s, 1H, CH triazole); 8.1–8.4 (m, 3H, ArHs,
CH pyrrole); 7.5 (d, 1H, CH pyrrole); 7.0–7.3 (m, 3H,
ArH’s); 6.9 (m,1H, CH pyrrole); 2.8 (s, 3H, CH3)
(TFA): 8.1–8.4 (m, 3H, ArH’s, CH pyrrole); 7.5 (d, 1H,
CH pyrrole); 7.0–7.3 (m, 3H, ArH’s); 6.9 (m,1H,
CH pyrrole); 3.0 (s, 3H, CH3); 2.8 (s, 3H, CH3)
(TFA): 8.1–8.4 (m, 3H, ArH’s, CH pyrrole); 7.5 (d, 1H,
CH pyrrole); 7.0–7.3 (m, 3H, ArH’s); 6.9 (m, 1H,
CH pyrrole); 2.8 (s, 3H, CH3)
3400 (NH);
1600 (C N)

Synthesis of Novel Pyrrylthieno[2,3-d]pyrimidines
317
Condensation of Compound 3a with Aromatic
Aldehydes; Formation of Chalcones 4a--c
A mixture of 3a (3.33 g, 0.01 mol) and the respective aldehyde (0.01 mol)
in an ethanolic sodium hydroxide solution 8% (50 mL) was stirred at
room temperature for 2 h. The solid that precipitated was collected and
recrystallized to give 4a–c.
Condensation of Compound 3a with Phenylhydrazine
or Thiosemicarbazide; Formation of Phenylhydrazone
5a or Thiosemicarbazone 5b
A mixture of 3a (3.33 g, 0.01 mol) and phenylhydrazine or thiosemi-
carbazide (0.01 mol) in glacial acetic acid (30 mL) was heated under
reflux for 1 h. The precipitate that formed after cooling was collected
and recrystallized to give 5a or 5b respectively.
4-Methyl-2-phenyl-5-(1-pyrryl)-thieno[2,3-d]-
pyrimidine-6-carbohydrazide (6)
A mixture of the ester 3c (3.63 g, 0.01 mol) and hydrazine hydrate 99%
(2 mL, 0.04 mol) in pyridine (30 mL) was heated under reflux for 3 h.
The reaction mixture was cooled and diluted with ice-water (30 mL)
whereby a white solid precipitated. It was collected by filtration and
crystallized to give 6.
6-(5-Aryl-2-pyrazolin-3-yl)-4-methyl-2-phenyl-5-
(1-pyrryl)-thieno[2,3-d]pyrimidines (7a--c)
A suspension of 4a–c (0.005 mol) and hydrazine hydrate 99% (1 mL,
0.02 mol) in ethanol (35 mL) was heated under reflux for 4 h. The pre-
cipitate that formed on cooling was collected and recrystallized to give
7a–c.
6-(5-Aryl-1-phenyl-2-pyrazolin-3-yl)-4-methyl-2-
phenyl-5-(1-pyrryl)-thieno[2,3-d]pyrimidines (8a--c)
A mixture of 4a–c (0.005 mol) and phenylhydrazine (0.54g, 0.005 mol)
in glacial acetic acid (25 mL) was heated under reflux for 3 h. The
precipitate that formed after cooling was collected and recrystallized to
give 8a–c.

318
E. A. Bakhite et al.
6-(5-Aryl-2-isoxazolin-3-yl)-4-methyl-2-phenyl-5-
(1-pyrryl)-thieno[2,3-d]pyrimidines (9a--c)
To a suspension of 4a–c (0.01 mol) and hydroxylamine hydrochloride
(0.7 g, 0.01 mol) in ethanol (35 mL), anhydrous sodium acetate (1.64 g,
0.02 mol) was added. The resulting mixture was heated under reflux for
4 h, cooled, and poured onto ice water (30 mL). The precipitated solid
was collected and recrystallized to give 9a–c.
6-(6-Aryl-1,2,3,6-tetrahydro-2-thioxopyrimidin-4-yl)-4-
methyl-2-phenyl-5-(1-pyrryl)-thieno[2,3-d]-
pyrimidines (10a--c)
To a suspension of 4a–c (0.005 mol) and thiourea (0.35 g, 0.005 mol) in
ethanol (30 mL), few drops of concentrated HCl was added. The result-
ing mixture was heated under reflux for 4 h and then left to cooled. The
precipitated solid was collected and recrystallized to give 10a–c.
Reaction of Thiosemicarbazone 5b with Phenacyl
Bromide, p-Chlorophenacyl Bromide, Ethyl
Chloroacetate or Methyl 2-bromopropionate; Formation
of Thiazolines 11a,b and Thiazolidinones 12a,b
To a mixture of 5b (2.03 g, 0.005 mol) and the respective halocompound
(0.005 mol) in ethanol (25 mL), fused sodium acetate (0.82 g, 0.01 mol)
was added. The resulting mixture was heated under reflux for 4 h and
then allowed to cool. The solid that formed was collected and recrystal-
lized to give 11a,b or 12a,b respectively.
N1-Arylmethylene-4-methyl-2-phenyl-5-(1-pyrryl)-
thieno[2,3-d]pyrimidine-6-carbohydrazides (13a--c)
A mixture of carbohydrazide 6 (1.75 g, 0.005 mol) and the respective
aldehyde (0.005 mol) in ethanol (20 mL) was heated under reflux for
3 h. The precipitate that separated after cooling was collected and
recrystallized to give 13a–c.
6-(4-Acetyl-4,5-dihydro-5-phenyl-1,3,4-oxadiazol-2-yl)-
4-methyl-2-phenyl-5-(1-pyrryl)-thieno[2,3-d]-
pyrimidine (14)
Compound 13a (0.87 g, 0.002 mol) in redistilled acetic anhydride
(20 mL) was heated under reflux for 4 h. The reaction mixture was

Synthesis of Novel Pyrrylthieno[2,3-d]pyrimidines
319
cooled, diluted with water (20 mL), and then allowed to stand at room
temperature for 3 h. The white solid that formed was collected and
recrystallized to give 14.
6-(3,5-Dimethyl-1H-pyrazol-1-yl)carbonyl-4-methyl-
2-phenyl-5-(1-pyrryl)-thieno[2,3-d]pyrimidine (15)
A mixture of carbohydrazide 6 (1.75 g, 0.005 mol) and acetylacetone
(5 mL, 0.05 mol) was heated under reflux for 30 min, then triturated
with ethanol (10 mL), and left to cool. The precipitate that formed was
collected and recrystallized to give 15.
1-(4-Methyl-2-phenyl-5-(1-pyrryl)-thieno[2,3-d]-
pyrimidin-6-yl)carbonyl-4-phenylthiosemicarbazide (16)
A mixture of carbohydrazide 6 (2.09 g, 0.006 mol) and phenyl isoth-
iocyanate (0.72 mL, 0.006 mol) in ethanol (25 mL) was heated under
reflux for 3 h. The precipitate that separated after cooling was collected
and recrystallized to give 16.
6-(4-Phenyl-5-thioxo-s-triazolin-3-yl)-4-methyl-
2-phenyl-5-(1-pyrryl)-thieno[2,3-d]pyrimidine (17)
A suspension of thiosemicarbazide 16 (2.42 g, 0.005 mol) in sodium
hydroxide solution 8% (20 mL) was heated under reflux on a steam bath
for 4 h, cooled, and filtered. The clear filtrate was acidified with dilute
HCl at 5–10 C. The solid that separated was collected and crystallized
to give 17.
6-(4,5-Dihydro-5-thioxo-1,3,4-oxadiazol-2-yl)-
4-methyl-2-phenyl-5-(1-pyrryl)-thieno[2,3-d]-
pyrimidine (18)
A mixture of carbohydrazide 6 (1.75 g, 0.005 mol) and carbon disul-
fide (3 mL) in ethanol (40 mL) containing potassium hydroxide
(0.45 g, 0.008 mol) was heated under reflux on a steam bath for
5 h. The reaction mixture was concentrated, diluted with water,
and filtered. The clear filtrate was acidified with dilute HCl at
5–10 C. The precipitated solid was collected and crystallized to
give 18.

320
E. A. Bakhite et al.
Reaction of Thiones 17 and 18 with Ethyl Chloroacetate;
Formation of Esters 19a,b
To a mixture of 17 or 18 (0.002 mol) and ethyl chloroacetate (0.22 mL,
0.002 mol) in ethanol (20 mL), sodium acetate trihydrate (0.68 g, 0.005
mol) was added. The resulting mixture was heated under reflux for
2 h, cooled, and diluted with water (10 mL). The solid that formed was
filtered off, washed thoroughly with water, and recrystallized to give
19a or 19b respectively.
4-Methyl-2-phenyl-5-(1-pyrryl)-thieno[2,3-d]-
pyrimidine-6-carboazide (20)
To a chilled suspension of carbohydrazide 6 (3.49 g, 0.01 mol) in glacial
acetic acid (25 mL), a cold solution of sodium nitrite 33% (10 mL) was
added dropwise with stirring. After completion of addition, the stir-
ring was continued for additional 1 h. The precipitate that formed was
collected by filtration, dried in air, and applied in the next reactions
without purification.
Reaction of Acid Azide 20 with Alcohols; Formation
of Alkyl Carbamate 22a,b
The acid azide 20 (0.72 g, 0.002 mol) in ethanol or iso-propanol (20 mL)
was heated under reflux for 5 h, concentrated, and then allowed to cool.
The precipitated solid was collected and recrystallized to give 22a or
22b respectively.
Reaction of 20 with Different Amines; Formation
of Urea Derivatives 23a--f
A mixture of acid azide 20 (0.72 g, 0.002 mol) and an excess amount
of the respective amine (ethanolamine, aniline, o-toluidine, p-toluidine,
p-anisidine or p-chloroaniline) (0.01 mol) was heated gently for 2 h,
triturated with ethanol (15 mL), and then allowed to cool. The precipi-
tated solid was collected and recrystallized to give 23a–f.
4-Methyl-2-phenylpyrrolo[100,200 :10,60 ]pyrazino-
[20,30 :4,5]thieno[2,3-d]pyrimidine-9(10 H)-one (24)
A suspension of 20 (3.6 g, 0.01 mol) in dry xylene (50 mL) was heated
under reflux for 2 h. The solid that formed while hot was collected and
recrystallized to give 24.

Synthesis of Novel Pyrrylthieno[2,3-d]pyrimidines
321
4-Methyl-2-phenylpyrrolo[100,200 :10,60 ]pyrazino-
[20,30 :4,5]thieno[2,3-d]pyrimidine-9(10 H)-thione (25)
A mixture of 24 (1.66 g, 0.005 mol) and phosphorus pentasulfide (1.11 g,
0.005 mol) in dry pyridine (20 mL) was heated under reflux for 5 h.
The reaction mixture was cooled, diluted with ice-water (40 mL), and
acidified with dilute acetic acid. The precipitate that formed was col-
lected and crystallized to give 25.
4-Methyl-2-phenyl-9-substituted methylthiopyrrolo-
[100,200 :10,60 ]pyrazino[20,30:4,5]thieno[2,3-d]-
pyrimidines (26a,b)
To a mixture of 25 (0.70 g, 0.002 mol) and p-chlorophenacyl bromide
or ethyl chloroacetate (0.002 mol) in ethanol (25 mL), sodium acetate
trihydrate (0.54 g, 0.004 mol) was added. The resulting mixture was
heated under reflux for 2 h and then left to cool. The solid that formed
was filtered off, washed thoroughly with water, and recrystallized to
give 26a or 26b respectively.
4-Methyl-2-phenylpyrrolo[100,200 :10,60 ]pyrazino-
[20,30 :4,5]thieno[2,3-d]pyrimidin-9-
ylthioacethydrazide (27)
A mixture of compound 26b (0.87 g, 0.002 mol) and hydrazine hy-
drate 99% (0.3 mL, 0.006 mol) in ethanol (15 mL) was allowed to stand
overnight at room temperature. The solid that formed was filtered off,
washed thoroughly with water and recrystallized to give 27.
9-Chloro-4-methyl-2-phenylpyrrolo[100 ,200 :10 ,60 ]-
pyrazino[20 ,30 :4,5]thieno[2,3-d]pyrimidine (28)
Compound 24 (3.32 g, 0.01 mol) in an excess amount of phosphorus
oxychloride (60 mL) was heated under reflux for 4 h and then left to
cool. The reaction mixture was poured gradually onto ice water (180 mL)
with stirring. The solid that formed was filtered off, washed thoroughly
with water, and crystallized to give 28.
9-Hydrazino-4-methyl-2-phenylpyrrolo[100,200 :10,60 ]-
pyrazino[20,30 :4,5]thieno[2,3-d]pyrimidine (29)
A mixture of the ester 26b (0.87 g, 0.002 mol) and hydrazine hydrate
99% (3 mL, 0.06 mol) was heated under reflux for 3 h. The solid that
formed while hot was collected and recrystallized to give 29.

322
E. A. Bakhite et al.
A mixture of chlorocompound 28 (1.75 g, 0.005 mol) and hy-
drazine hydrate 99% (1 mL, 0.02 mol) in ethanol (30 mL) was
heated under reflux for 3 h. The solid that formed while hot upon
recrystallization was identical to that described the method above
(yield: 93%).
4-Methyl-2-phenyl-s-triazolo[4000,3000 :40,50 ]pyrrolo-
[100, 200 :10,60 ]pyrazino[20,30 :4,5]thieno[2,3-d]pyrimidine
(30a)
A suspension of hydrazino compound 29 (0.35 g, 0.001 mol) in triethyl
orthoformate (10 mL) was heated under reflux for 3 h. The solid that
formed while hot was collected and recrystallized to give 30a.
4,11-Dimethyl-2-phenyl-s-triazolo[4000,3000 :40,50 ]-
pyrrolo[100,200 :10,60 ]pyrazino[20,30 :4,5]thieno[2,3-d]-
pyrimidine (30b)
A suspension of hydrazino compound 29 (0.35 g, 0.001 mol) in glacial
acetic acid (15 mL) was heated under reflux for 3 h. The solid that
formed on cooling was collected and recrystallized to give 30b.
4-Methyl-2-phenyl-s-triazolo[4000,3000 :40,50 ]pyrrolo-
[100,200 :10,60 ]pyrazino[20,30 :4,5]thieno[2,3-d]pyrimidine-
11-thiol (30c)
A mixture of hydrazino compound 29 (0.35 g, 0.001 mol) and carbon
disulfide (1 mL) in pyridine (10 mL) was heated under reflux on a steam
bath for 8 h. The solid that formed on cooling was collected and recrys-
tallized to give 30c.
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