Synthesis and reactions of some new heterocyclic compounds related to pyrrolylthieno[2,3-d]pyrimidines and thieno[2,3-d][4,5-d]dipyrimidines

Article abstract of DOI:10.1080/10426500590906067

Condensation of ethyl-5-amino-2,4-diphenylthieno[2,3-d]pyrimidine-6- carboxylate (3a) with 2,5-dimethoxy tetrahydrofurane in acetic acid gives the corresponding 5-pyrrolyl derivative 4, which in turn could be easily reacted with hydrazine hydrate in ethan

Full text of DOI:10.1080/10426500590906067

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Phosphorus, Sulfur, and Silicon
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Synthesis and Reactions
of Some New Heterocyclic
Compounds Related
to Pyrrolylthieno[2,3-
d]pyrimidines and Thieno[2,3-
d][4,5-d]dipyrimidines
Maisa I. Abdel Moneam a
a Chemistry Department, Faculty of Science, , Assiut
University , Egypt
Published online: 21 Dec 2010.
To cite this article: Maisa I. Abdel Moneam (2005) Synthesis and Reactions of Some
New Heterocyclic Compounds Related to Pyrrolylthieno[2,3-d]pyrimidines and
Thieno[2,3-d][4,5-d]dipyrimidines, Phosphorus, Sulfur, and Silicon and the Related
Elements, 180:2, 633-646, DOI: 10.1080/10426500590906067
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Phosphorus, Sulfur, and Silicon, 180:633–646, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500590906067
Synthesis and Reactions of Some New Heterocyclic
Compounds Related to Pyrrolylthieno[2,3-d]pyrimidines
and Thieno[2,3-d][4,5-d]dipyrimidines
Maisa I. Abdel Moneam
Chemistry Department, Faculty of Science, Assiut University, Egypt
Condensation of ethyl-5-amino-2,4-diphenylthieno[2,3-d]pyrimidine-6-carboxylate
(3a) with 2,5-dimethoxy tetrahydrofurane in acetic acid gives the corresponding 5-
pyrrolyl derivative 4, which in turn could be easily reacted with hydrazine hydrate
in ethanol yielding the carbohydrazide derivative 5. Reaction of 5 with aromatic
aldehydes, acetylacetone, carbon disulfide or phenylisothiocyanate gave pyrrolyl
derivatives 6, 7, 8, 9 respectively. On the other hand, condensation of 5-(1-pyrrolyl)-
6-acetyl-2,4-diphenylthieno[2,3-d]pyrimidine 11 with benzaldehyde afforded the
corresponding chalcone 12, which on treatment with hydrazine hydrate, phenyl hy-
drazine, or thiourea gave the pyrazolinyl derivatives 13, 14 and pyrimidinyl deriva-
tive 15, respectively. Furthermore some new pyrimidothienopyrimidne 16, 17a–d,
19, 20a–c were obtained using 5-amino-carboxamide 3c as starting material.
Keywords Pyrimidothienopyrimidine; pyrrolylthienopyrimidine; thienopyrimidine
INTRODUCTION
The structural diversity and biological significance of fused pyrimidines
have a roused much attention in the past few years owing to their wide
range of biological activity.1 Many potential drugs have been modeled on
them, particularly in cancer and virus research.2 Also, thienodipyrim-
idines show anaphylactic activity,3 while thieno[2,3-d]pyrimidine prove
to exhibit antituberculouses4 and to, herpes virus inhibitory5 and can
be used in fertility regulation therapies.6 On the other hand many
pyrroles have been investigated in relation to their pharmacological ac-
tivities, they prove to exhibit anti-inflammatory activities,7 antitumer8
and antibiotic which show activity against various microorganisms.9
Within this context and also as a part of our research program deal-
ing with the syntheses of several thieno[2,3-d]pyrimidines,10,11 the
present work was planned to investigate new route for the synthesis of
Received April 20, 2004; accepted June 30, 2004.
Address correspondence to Maisa I. Abdel Moneam, Chemistry Department, Faculty of
Science, Assiut University, Assiut 71516, Egypt. E-mail: maisaabdelmonem@hotmal.com
633

634
M. I. A. Moneam
novel thieno[2,3-d]pyrimidines, pyrrolylthieno[2,3-d]pyrimidines and
thieno[2,3-d][4,5-d]dipyrimidines with potential biological activities
DISCUSSION
The starting 5-Cyano-2,6-diphenylpyrimidine-4(3H)thione (1) was
readily obtained by previously described procedure.12 Compound 1
was reacted with different α-halocompounds namely; ethyl chloroac-
etate, chloroacetone, chloroacetamide, phenacyl bromide and chloroac-
etanilide in refluxing ethanol containing sodium acetate to give the
expected 5-alkyl derivatives 2a–e in excellent yield. The latter com-
pounds 2a–e were cyclized to the required compounds 3a–e by heating
in ethanol containing sodium ethoxide (Scheme 1).
SCHEME 1
Compound 3a was condensed with 2,5-dimethoxytetrahydorofurane
in acetic acid to give the corresponding 5-pyrrolyl derivative 4,13 which
in turn could easily be reacted with hydrazine hydrate in ethanol af-
fording the carbohydrazide derivative 5. Condensation of 5 with aro-
matic aldehydes in refluxing ethanol afforded the hydrazone deriva-
tives 6a–d. Similarly, reaction of 5 with acetylacetone furnished the
dimethylpyrazolyl derivative 7 (Scheme 3).
Carbohydrazide 5 reacted with carbon disulfide in pyridine afforded
oxadiazolyl thione 8. Furthermore, when 5 was allowed to react with

Synthesis and Reactions of New Pyrrolylthienopyrimidines
635
SCHEME 2
phenylisothiocyanate in absolute ethanol, the product was identified
as Nꢀ-5-(1-pyrrolyl)-N4-phenyl-2,4-diphenylthieno[2,3-d]pyrimidin-6-
yl)carbonylthio-semicarbazide (9). Cyclization of thiosemicarbazide 9
into triazolyl derivative 10 was achieved in alcoholic sodium hydroxide
solution (Scheme 3).
SCHEME 3

636
M. I. A. Moneam
Other new pyrrolylthieno[2,3-d]pyrimidines were obtained using 5-
amino-6-acetyl-2,4-diphenyl thieno[2,3-d]pyrimidine (3b) as starting
material. Thus, 3b was condensed with DMTHF in acetic acid to give the
corresponding pyrrolyl derivative 11 which was allowed to undergo base
catalysed Claisen-Schmidt reaction with benzaldehyde to give chalcone
derivative 12 was produced in good yield. The reactivity of 12 as chol-
cone was tested via their cyclocondensation reactions with hydrazines
and thiourea affording pyrazolyl 13, 14 and pyrimidinyl 15 derivatives,
respectively (Scheme 4).
SCHEME 4
5-Amino-2,4-diphenylthieno[2,3-d]pyrimidine-6-carboxamide (3c)
proved also to be a versatile synthon for some new fused thienopy-
rimidine moieties. Thus the reaction of 3c with carbon disulfide in
hot pyridine led to the formation of oxopyrimidothienopyrimidine
16, which was easily S-alkylated with different halo compounds in
ethanol containing catalytic amount of sodium acetate to give the
expected S-alkylated products 17a–d in good yields. Compound 17c
underwent smooth cyclodehydration in concentrated sulfuric acid14
to furnish thiazolopyrimidothienopyrimidine 18 in moderate yield
(Scheme 5).

Synthesis and Reactions of New Pyrrolylthienopyrimidines
637
SCHEME 5
Treatment of 16 with hydrazine hydrate in pyridine led to the
formation of 2,4-diphenyl-6-hydrazinothieno[2,3-d][4,5-d]dipyrimidin-
8(7H)-one (19), which reacts easily with aromatic aldehydes in
ethanol to give the corresponding hydrazones 20a–c. Condensa-
tion of 19 with triethylorthoformate in ethanol in presence of
few drops of acetic acid afforded the triazolo derivative 2115
(Scheme 6).
The structural formulae of all newly synthesized compounds were
elucidated and confirmed by elemental and spectroscopic analyses (cf.
Tables I, II).
EXPERIMENTAL
All melting points are uncorrected and measured on a Fisher-Johns
apparatus. IR spectra: Shimadzu IR-Spectrophotometer (KBr; νmax in
1
Cm−1); H-NMR spectra: Varian EM-390, 90 MHz spectrometer, TMS
as internal standard; MS: Jeol JMS-600; elemental analyses (C, H, N):
Perkin. Elmer 240c elemental analyzer: sulpher and chlorine analysis:
oxygen flask method by the Micro Analytical Unite at Assiut University.

638
M. I. A. Moneam
SCHEME 6
Reaction of 1 with Ethyl Chloroacetate, Chloroacetone,
Chloroacetamide, Phenacyl Bromide or Chloroacetanilide
Formation of Compounds 2a–e, General Procedure
A mixture of compound 1 (0.02 mol), sodium acetate (4.68 g, 0.03 mol)
and the respective halo-compound (0.02 mol) in ethanol (100 ml) was
heated under reflux for 2 h. The precipitate that formed on cooling was
collected and recrystallized from ethanol to give 2a–e.
Cyclization of Compounds 2a–e; Formation of 3a–e;
General Procedure
Compounds 2a–e (0.01 mol) in sodium ethoxide solution (50 mg Na in
25 ml absolute ethanol) was heated under reflux for 15 mins. The solid
that formed while hot was collected and recrystallized from ethanol to
give yellow crystals 3a–e.
Ethyl 2,4-diphenyl-5-(1-pyrrolyl)thieno[2,3-d]pyrimidine-6-
carboxylate (4)
A mixture of 3a (3.75 g; 0.01 mol) and 2, 5-dimethoxytetrahy-
drofurane (0.01 mol) was refluxed in acetic acid (20 ml) for 3 h and
then allowed to cool. The solvent was removed under reduced pressure
and the residue was triturated several times with ethanol. The solid
product was filtered off and recrystallized from acetic acid as pale yel-
low crystals of 4.

Synthesis and Reactions of New Pyrrolylthienopyrimidines
639
TABLE I Melting Points, Yield and Analytical Data (Calc/Found) of
the Prepared Compounds
M. P.
[◦C]
Yield
[%]
Mol. Formula
(Mol. Wt)
Comp.
C
H
N
S
2a
155–157
160–161
173–175
178–180
244–245
184–185
229–230
259–260
209–210
194–195
178–180
229–230
288–290
298–300
278–280
308–310
145–147
188–200
248–250
259–260
173–175
164–165
89
91
88
85
87
85
81
83
85
85
79
76
71
73
71
75
73
72
77
65
79
87
C21H17N3O2S
(375.43)
67.18
67.35
69.56
69.71
65.90
65.77
73.71
73.56
71.09
71.17
67.18
67.33
69.56
69.17
65.90
66.04
73.71
73.54
71.09
71.26
70.59
70.32
67.15
67.54
72.13
72.48
70.30
70.09
67.48
67.94
70.84
70.33
70.71
70.32
63.57
63.09
65.90
65.64
68.17
68.43
72.89
72.62
76.99
77.21
4.48
4.41
4.34
4.11
4.07
4.31
4.17
4.03
4.26
4.32
4.48
4.06
4.34
4.03
4.07
4.51
4.17
4.22
4.26
4.41
4.47
4.77
4.13
4.47
4.23
4.42
4.37
4.50
3.77
3.31
4.83
4.50
4.42
4.47
3.31
3.11
4.05
4.30
3.81
3.25
4.32
4.08
4.37
4.29
11.19
11.27
12.17
12.52
16.18
16.35
10.31
10.55
13.27
13.52
11.19
11.52
12.17
12.52
16.18
16.39
10.31
10.82
13.27
13.18
9.87
8.54
8.73
9.27
9.36
9.24
9.09
7.86
7.34
7.58
7.74
8.54
8.72
9.27
8.87
9.24
9.58
7.86
7.71
7.58
7.98
7.52
7.83
7.78
7.57
6.41
6.12
6.05
6.21
6.00
5.82
5.91
6.07
6.73
6.61
14.12
13.97
11.72
11.44
12.13
12.32
8.10
8.37
6.63
6.94
2b
2c
2d
2e
3a
3b
3c
3d
3e
4
C
20H15N3OS
(345.41)
C
19H14N4OS
(346.29)
C25H17N3OS
(407.48)
C
25H18N4OS
(422.35)
C
21H17N3O2S
(375.43)
C
20H15N3OS
(345.41)
C
19H14N4OS
(346.29)
C
C
25H17N3OS
(407.48)
25H18N4OS
(422.35)
C25H19N3O2S
(425.34)
9.90
5
C
23H17N5OS
(411.34)
17.02
16.94
14.02
13.90
13.22
13.49
13.11
13.05
15.49
15.39
14.73
14.06
15.44
15.15
15.37
15.05
15.90
16.07
10.62
10.34
8.68
6a
6b
6c
6d
7
C
30H21N5OS
(499.51)
C
31H23N5O2S
(529.60)
C
30H20N5OSCl
(533.96)
C32H26N6OS
(542.51)
C
28H21N5OS
(475.56)
8
C
24H15N5OS2
(453.41)
9
C30H22N6OS2
(546.73)
10
11
12
C
30H20N6S2
(528.50)
C24H17N3OS
(395.47)
C
31H21N3OS
(483.58)
8.26
(Continued on next page)

640
M. I. A. Moneam
TABLE I Melting Points, Yield and Analytical Data (Calc/Found) of
the Prepared Compounds (Continued)
M. P.
[◦C]
Yield
[%]
Mol. Formula
(Mol. Wt)
Comp.
C
H
N
S
13
193–195
223–225
183–185
308–310
258–260
280–282
263–265
>300
71
73
75
84
87
85
87
81
63
79
73
73
71
69
C31H23N5S
(497.61)
74.82
74.57
77.46
77.62
70.97
70.49
61.85
61.64
62.16
62.46
60.74
61.27
66.38
65.62
64.47
64.37
68.86
68.41
62.18
61.94
68.36
68.09
66.67
66.70
63.71
63.88
63.65
63.41
4.65
4.81
4.70
4.21
4.27
4.62
3.08
3.46
3.65
3.13
3.82
3.96
3.58
3.85
3.67
3.41
3.27
3.45
3.62
3.31
3.79
3.46
3.96
3.34
3.34
3.13
3.02
3.52
14.07
14.33
12.20
12.65
12.93
12.50
14.42
14.61
12.60
12.06
11.80
11.07
11.05
11.07
13.42
13.37
11.74
11.62
21.75
21.52
17.71
17.63
16.66
16.17
16.51
16.94
21.20
20.93
6.44
6.09
5.58
14
C
37H27N5S
(573.71)
5.37
15
C
32H23N5S2
(541.51)
11.84
11.60
16.51
16.45
13.99
14.43
13.51
13.30
12.65
13.13
12.29
12.06
13.11
12.97
8.30
8.11
6.75
6.46
6.35
6.09
6.29
6.18
8.07
16
C20H12N4OS2
(388.36)
C23H16N4O2S2
(444.40)
C24H18N4O3S2
(474.52)
28H18N4O2S2
(506.58)
17a
17b
17c
17d
18
C
C28H19N5O2S2
(521.59)
298–300
283–285
>360
C
28H16N4OS2
(492.45)
19
C
20H14N6OS
(386.31)
20a
20b
20c
21
C27H18N6OS
(474.39)
>360
C
28H20N6O2S
(504.39)
>300
C
27H17N6OSCl
(508.5)
>300
C
21H12N6OS
(396.26)
7.89
2,4-Diphenyl-5-(1-pyrrolyl)thieno[2,3-d]pyrimidine-6-
carbohydrazide (5)
A mixture of 4 (4.25 g; 0.01 mol) and hydrazine hydrate (3 ml) in ethanol
(20 ml) was refluxed for 3 h. The solid product which formed in hot
mixture was filtered off and crystallized from dioxane as orange crystals
from 5.
Arylidine 2,4-diphenyl-5-(1-pyrrolyl)thieno[2,3-d]pyrimidine-6-
carbohydrazone (6a–d)
A mixture of carbohydrazide 5 (4.11 g; 0.01 mol) and appropriate aro-
matic aldehyde (0.01 mol) in ethanol (30 ml) was refluxed for 4 h, then

Synthesis and Reactions of New Pyrrolylthienopyrimidines
641
TABLE II IR, 1HNMR and Mass Spectral Data
Compd.
No
IR [Cm−1
]
1HNMR [ppm]
2a
2900( CH aliphatic); 2200 (DMSO-d6): 7.3–8.2 (m, 10H, Ar H); 4.5 (s, 2H,
(C N); 1710 (C O)
SCH2); 3.7–3.9 (q, J = 7.0, 2H, CH2 ester); 1.2–1.3
(t, J = 7.0, 3H, CH3 ester)
2b
2c
2200 (C N); 1690 (C O)
(DMSO-d6): 7.2–8.2 (m, 10H, Ar H); 3.9 (s, 2H,
SCH2); 2.4 (s, 3H, CH3)
3400–3300 (NH2); 2200
(C N); 1670 (C O)
2200 (C N); 1670 (C O)
3200 (NH); 2200 (C N);
1670 (C O)
(DMSO-d6): 7.5–8.5 (m, 10H, Ar H); 4.2 (s, 2H,
SCH2); 5.6 (s, 2H, NH2)
(DMSO-d6): 7.2–8.5 (m, 15H, Ar H); 5.1 (s, 2H, SCH2)
(DMSO-d6): 11.0 (s, 1H, NH); 7.5–8.7 (m, 15H, Ar H);
4.3 (s, 2H, SCH2)
2d
2e
3a
3400, 3310 (NH2); 2900
(DMSo-d6): 7.3–8.1 (m, 10H, Ar H); 5.5 (s, 2H, NH2);
3.3–3.5 (q, J = 7.0, 2H, CH2, ester); 1.3–1.5 (t,
J = 7.0, 3H, CH3 ester)
(
CH aliphatic); 1710
(C O)
3480–3300 (NH2); 1690
(C O)
3400–3300 (NH2); 1670
(C O)
3450–3300 (NH2); 1690
(C O)
3100, 3450, 3300 (NH,
NH2) 1670 (C O)
2950 ( CH aliphatic); 1715 (CDCl3): 7.5–8.6 (m, 10H, Ar H) 6.3–6.5 (m, 2H, 2CH
3b
3c
3d
3e
4
(DMSo-d6): 7.5–8.8 (m, 10H, Ar H) 5.9 (s, 2H, NH2);
2.5 (s, 3H, CH3)
—
(DMSo-d6): 7.3–8.5 (m, 15H, Ar H); 5.5 (s, 2H, NH2)
(DMSo-d6): 10.7 (s, 1H, NH); 7.5–8.9 (m, 15H, Ar H);
5.8 (s, 2H, NH2)
(C O)
pyrryl); 5.7–5.9 (m, 2H, 2CH pyrryl); 4.2 (q, J = 7.0,
2H, CH2, ester); 1.3–1.5 (t, J = 7.0, 3H, CH3 ester)
(DMSO-d6): 9.5 (s, 1H, NH); 7.5–8.6 (m, 10H, Ar H);
6.1–6.3 (m, 2H, 2CH pyrryl); 5.6–5.8 (m, 2H, 2CH
pyrryl); 5.5(s, 2H, (NH2)
5
3310, 3300, 3230
(
NHNH2) 1650 (C O)
6a
6b
3180 (NH); 1650 (C O)
(DMSO-d6): 9.3 (s, 1H, NH); 7.3–8.9 (m, 16H, Ar H +
N
CH); 5.7–5.9 (m, 2H, 2CH pyrryl); 6.2–6.5 (m,
2H, 2CH pyrryl)
3170 (NH); 1645 (C O)
(DMSO-d6): 9.5 (s, 1H, NH); 7.5–8.8 (m, 16H, Ar H +
N
CH); 5.8–6 (m, 2H, 2CH pyrryl); 6.2–6.3 (m,
2H, 2CH pyrryl); 3.5 (s, 3H, OCH3)
—
6c
6d
7
3170 (NH); 1650 (C O)
3170 (NH); 1650 (C O)
1650 (C O); 1590 (C N)
—
(DMSO-d6): 7.2–8.3 (m, 10H, Ar H); 6.2–6.4 (m, 2H,
2 CH pyrryl); 6.1 (s, 1H1 CH pyrazole); 5.9–6.0 (m,
2H, 2-CH pyrryl); 2.4, 2.2 (2s, 6H, 2CH3)
(DMSO-d6): 10.1 (s, 1H, NH); 7.7–8.5 (m, 10H, Ar H);
5.9–6.1 (m, 2H, 2CH pyrryl); 6.2–6.5 (m, 2H, 2CH
pyrryl)
8
3210 (NH); 1610 (C N)
9
3310, 3200, 3150 (3NH)
1640 (C O); 1590 (C N)
(DMSO-d6): 9.5(s, 2H, 2NH); 10.3 (s, 1H, NH); 7.3–8.6
(m, 15H, Ar H); 5.9–6.1 (m, 2H, 2CH pyrryl);
6.2–6.4 (m, 2H, 2CH pyrryl)
(DMSO-d6): 9.5 (s, 1H, NH); 7.8–8.9 (m, 15H, Ar H);
6.2–6.4 (m, 2H, 2CH pyrryl); 5.6–5.8(m, 2H, 2CH
pyrryl).
10∗
3210 (NH); 1600 (C N)
(Continued on next page)

642
M. I. A. Moneam
TABLE II TR, 1HNMR and Mass Spectral Data (Continued)
Compd.
No
IR [Cm−1
1660 (C O)
]
1HNMR [ppm]
11
(DMSO-d6): 7.7–8.9 (m, 10H, Ar H); 6.1–6.3 (m, 2H1
2CH pyrryl); 5.8–5.6 (m, 2H, 2CH pyrryl); 2.7 (s,
3H, COCH3)
(DMSO-d6): 7.9–8.2 (m, 17H, Ar H and CH CH );
6.2–6.1 (m, 2H, 2CH pyrryl); 6.5–6.3 (m, 2H, 2CH
pyrryl)
12∗
13
1660 (C O) and 1590
(C N)
3200 (NH) and 1590 (C N) (DMSO-d6): 12.1 (s, 1H, NH); 7.7–8.6 (m, 15H, Ar H);
5.9–6.1 (m, 2H, 2CH pyrryl); 6.4–6.2 (m, 2H, 2CH
pyrryl); 4.6–4.8(t, 1H, CH pyrazoline); 3.3–3.5 (m,
2H, CH2 pyrazoline)
1600(C N)
3320, 3100 (2NH); 1590
(C N) and 1230 (C S)
14∗
—
15∗∗
(DMSO-d6): 9.7, 10.5 (2s, 2H, 2NH); 7.5–8.8 (m, 17H,
15Ar H and 2CH pyrimidine); 6.1–6.3 (m, 2H, 2CH
pyrryl); 6.5–6.6 (m, 2H, 2CH pyrryl)
16
3400, 3100 (2NH) and 1660 (T.FA): 7.5–8.7 (m, 10H, Ar H)
(C O)
17a
17b
3200 (NH); 1680, 1640
(2C O) and 1610 (C N)
3290 (NH); 2900 ( CH
aliphatic); 1710, 1660
(2C O) and 1600 (C N)
3200 (NH); 1680 (C O) and
1600 (C N)
3220, 3100 (2NH); 1670
(C O) and 1590 (C N)
1690 (C O) and 1600
(C N)
(DMSO-d6): 10.3 (s, 1H, NH); 7.3–8.6 (m, 10H, Ar H);
4.5 (s, 2H, SCH2); 2.9(s, 3H, CH3)
(DMSO-d6): 10.1 (s, 1H, NH); 7.2–8.5 (m, 10H, Ar H);
4.5 (s, 2H, SCH2); 3.9 (q, 2H, CH2 ester); 1.5 (t,3H,
CH3 ester)
—
17c
17d
18∗∗
19
(DMSO-d6): 9.5, 10.3 (2s, 2H, 2NH); 7.3–8.6 (m, 15H,
Ar H); 4.6 (s, 2H, SCH2)
(TFA): 8.2 (s, 1H, thiazole-CH); 7.1–8 (m, 10H, Ar H)
3380, 3280, 3200 (NHNH2, (DMSO-d6): 9.5, 10.3 (2s, 2H, 2NH); 7.6–8.7 (m, 10H,
NH); 1670 (C O) and
1600 (C N)
Ar H); 4.7 (br, 2H, NH2)
20a
20b
20c
21∗
3310, 3200 (2NH); 1670
(C O) and 1610 (C N)
3320, 3200 (2NH); 1675
(C O) and 1600 (C N)
3310, 3200 (2NH) 1670
(C O) and 1590 (C N)
(DMSO-d6): 9.3, 10.1 (2s, 2H, 2NH); 7.2–8.6 (m, 16H,
Ar H and N CH)
(DMSO-d6): 9.5, 10.1 (2s, 2H, 2NH) 7.5–8.7 (m, 15H,
Ar H and
N
CH-); 2.7 (s, 3H, OCH3)
—
3400 (NH); 1670 (C O) and (DMSO-d6): 10.5 (s, 1H, NH); 8.6 (s, 1H, triazol CH);
1590 (C N) 7.2–8.5 (m, 10H, Ar H)
∗MS of 10: m/z (fragment, %): 529 (M+, 80); 463 (M+ C4H4N, 90).
∗MS of 12: m/z (fragment, %): 484 (M+, 56); 407 (M+ C6H5, 100).
∗MS of 14: m/z (fragment, %): 574 (M+, 60); 497 (M+ C6H5, 90).
∗MS of 15: m/z (fragment, %): 542 (M+, 45); 476 (M+ C4H4N, 85).
∗MS of 21: m/z (fragment, %): 396 (M+, 25); 395 (M+-1, 70);394 (M+ − 2, 73).
∗∗C13-NMR Spectra of compounds 15, 18 were recorded on a Jeol LA 400 MHzFT-
NMR Spectrometer.
∗∗C13-NMR of 15: 164, 166, 128, 130 (pyrimidine); 127, 137 (thiophene); 118, 110
(pyrryl); 103, 59, 149, 179 (thioxopyrimidine); 126–142 (Aromatic).
∗∗C13-NMR of 18: 163, 165, 127, 136 (pyrimidine); 144, 136 (thiophene) 163, 165
(pyimidinone); 86, 145 (thiazole); 127–136 (aromatic).

Synthesis and Reactions of New Pyrrolylthienopyrimidines
643
allowed to cool. The solid product was collected and crystallized from
ethanol into yellow–orange crystals from 6a–d.
6-[3ꢀ,5ꢀ-Dimethyl-pyrazoleylcarbonyl]-2,4-diphenyl-5-(1-
pyrrolyl)thieno[2,3-d]pyrimidine (7)
A mixture of 5 (4.11 g; 0.01 mol) and acetylacetone (1 g; 0.01 mol) in
ethanol in presence of few drops from AcOH was refluxed for 6 h the solid
product which separated was collected by filtration and recrystallized
from acetic acid to give yellow crystals of 7.
2,4-Diphenyl-5-(1-pyrrolyl)-6-(5ꢀ-thioxo-1,3,4-oxadiazol-2-
yl)thieno[2,3-d]pyrimidine 8
A mixture of compound 5 (4.11 g; 0.01 mol) and carbon disulfide (5 ml)
in pyridine (20 ml) was heated on a water bath for long time (12 h). The
solid product which separated from the hot mixture was collected by
filtration and recrystallized from dioxane as orange crystals from 8.
2,4-Diphenyl-6-(oxophenylthiosemicarbazide)-5-(1-pyrrolyl)-
N4-phenyl-2,4diphenylthieno[2,3-d]pyrimidin-6-
yl)carbonylthiothemicarbazide (9)
A mixture of 5 (4.11 g; 0.01 mol) and phenylisothiocyanate (1.35 g;
0.01 mol) in ethanol was refluxed for 4 h pale yellow crystalline product
obtained on heating was collected by filtration and recrystallized from
dioxane.
2,4-Diphenyl-6-(1,5-dihydro-4-phenyl-5-thioxo-s-triazol-3-yl)-
5-(1-pyrrolyl)thieno [2,3-d]pyrimidine (10)
Thiosemicarbazide 9 (5.46 g; 0.01 mol) was dissolved in 2N alcoholic
sodium hydroxide (20 ml) and heated for 3 h the solution was cooled
and acidified with dilute. HCl, the separated product was collected by
filtration and crystallized from dioxane as yellow crystals from 10.
2,4-Diphenyl-6-methylcarbonyl-5-(1-pyrrolyl)thieno[2,3-
d]pyrimidine (11)
This compound was synthesized following an analogous procedure that
for compound 4. Compound 11 was separated from dioxane as deep
yellow crystals.

644
M. I. A. Moneam
1 (2,4-Diphenyl-5-(1-pyrrolyl)thieno[2,3-d]pyrimidine-6-yl)-3-
phenyl-2-propen-1-one (12)
To a solution of 11 (3.95 g; 0.0l mol) in hot ethanol (100 ml) containing
sodium hydroxide (2 g, 0.05 mol), the benzaldehyde (1.06 g; 0.01 mol)
was added. The resulting mixture was stirred at 50–55 for 4 h and then
left to cool. The separated solid was collected and recrystallized from
dioxane to give orange crystals of 12.
2,4-Diphenyl-6-(5-phenyl-ꢀ2-pyrazolin-3-yl)-5-(1-pyrrolyl)-
thieno[2,3-d]pyrimidine (13)
A mixture of 12 (0.96 g; 0.002 mol) and hydrazine hydrate (3 ml) in
ethanol (30 ml) was heated under reflux for 4 h. The separated solid
product was collected and recrystallized from ethanol-CHCl3 mixture
to give yellow crystals of 13.
2,4-Diphenyl-6-(1,5-diphenylpyrazolin-3-yl)-5-(1-pyrrolyl)-
thieno[2,3-d]pyrimidine (14)
A mixture of 12 (4.83 g; 0.01 mol) and phenyl hydrazine (1.08 g; 0.01 mol)
in ethanol (30 ml) was heated under reflux. The solid product which
separated during heating was collected and recrystallized from ethanol-
CHCl3 mixture as orange crystals from 14.
2,4-Diphenyl-6-(2,3-dihydro-2-thioxo-1,3-pyrimidin-6-yl)-5-(1-
pyrrolyl)thieno[2,3-d]pyramidine (15)
A mixture of 12 (4.83 g; 0.01 mol) and thiourea (0.76 g; 0.01 mol) in
ethanol (30 ml), a few drops of piperidine were added. The reaction
mixture was heated under reflux for 4 h the precipitate that formed
while hot was collected by filtration and recrystallized from dioxane as
deep yellow crystals of 15.
2,4-Diphenyl-5,6-dihydro-6-thioxothieno[2,3-d][4,5-
d]dipyrimidin-8(7H)one (16)
A mixture of compound 3C (3.46 g;0.01 mol) and carbon disulfide (5 ml)
in pyridine (20 ml) was heated on water bath for 12 h. The solid prod-
uct which separated from hot mixture was collected by filtration and
crystallized from dioxane as orange needles from 16.

Synthesis and Reactions of New Pyrrolylthienopyrimidines
645
Reactions of 16 with Chloroacetone, Ethyl Chloroactate,
Phenacylbromide, and Chloroacetanilide
Formation of Compounds 17a–d; General Procedure
A mixture of compound 16 (3.88 g; 0.01 mol), sodium acetate (1.46 g;
0.02 mol) and respective halo compounds (0.01 mol) was heated under
reflux for 1–2 h. The precipitate that formed on cooling was collected
by filtration, washed with water and crystallized from ethanol-CHCl3
mixture as pale yellow crystals of 17a–d.
2,4,8-Triphenylthiazole[3ꢀꢀ,2ꢀꢀ:1ꢀ,2ꢀ]pyrimido[4’,5’:4,5]thieno-
[2,3-d]pyrimidin-9-one (18).
To a solution of 17c (1.0 g; 0.002 mol) in glacial acetic acid (15 ml),
concentrated H2SO4 (10 ml) was added and the mixture was gently
heated for 8 h. After cooling reaction mixture was poured into ice-water
and neutralized with 5% aqueous sod. bicarbonate. The precipitated
was filtered off, washed well with water and crystallized from dioxane
as yellow crystals of 18.
2,4-Diphenyl-6-hydrazinothieno[2,3-d][4,5-d]dipyrimidin-
8(7H)one (19)
A mixture of compound 16 (0.77 g; 0.002 mol) and 99% hydrazine hy-
drate (2 ml) in pyridine (10 ml) was heated under reflux for 10 h or till
H2S gas ceased, then allowed to cool. The solid product was collected,
washed well with ethanol and recrystallized from pyridine as orange
crystals of 19.
6-Arylidenehydrazion-2,4-diphenyl-5,6-dihydrothieno[2,3-d]-
[4,5-d]dipyrimidin-8 (7H)one (20a–c)
A mixture of 19 (3.86 g; 0.01 mol) and the respective aldehyde (0.01 mol)
in ethanol (25 ml) was refluxed for 3 h. The solid product that precipi-
tated by cooling was collected and recrystallized from dioxane as orange
crystals of 20a–c.
2,4-Diphenyl-6(H)-s-triazolo[3”,4”:1’,2’]pyrimido[4’,5’:4,5]-
thieno[2,3-d]pyrimidine (21)
A mixture of hydrazion derivative 19 (3.86 g; 0.01 mol) and triethy-
lorthoformate (0.12 mol) in ethanol in presence of few drops of acetic
acid, was refluxed for 3 h the solid product which separated from the

646
M. I. A. Moneam
hot mixture was filtered off and recrystallized from acetic acid as yellow
crystals of 21.
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