Synthesis and reactions of some new thienopyrimidines

Article abstract of DOI:10.1080/10426500307807

4-Methyl-6-mercapto-2-phenylpyrimidine-5-carbonitrile (1) was reacted with different halo compounds, namely ethylchloroacetate, chloroacetone, bromoacetanilide, p-chlorobromoacetanilide, and p-methoxy chloroacetanilide in ethanol in the presence of sodium acetate yielded the corresponding S-alkylated derivatives (2a-e). The latter compounds underwent cyclization into thienopyrimidines (4a-e) upon treatment with sodium ethoxide in ethanol. The reaction of (4a) with hydrazine hydrate led to the formation of 5-amino-4-methyl-2-phenylthieno[2,3-d]pyrimidine-2-carbohydrazide (5). Compound (5) was reacted with a variety of reagents to produce other new thienopyrimidines as well as oxadiazolylthienopyrimidines (6, 11).

Full text of DOI:10.1080/10426500307807

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Phosphorus, Sulfur, and Silicon and the Related
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Synthesis and Reactions of Some New
Thienopyrimidines
Maisa I. Abdel Moneam a , Ahmed A. Geies a , Galal M. El-Naggar a & Suliman M. Mussa a
a Assiut University , Assiut, Egypt
Published online: 27 Oct 2010.
To cite this article: Maisa I. Abdel Moneam , Ahmed A. Geies , Galal M. El-Naggar & Suliman M. Mussa (2003) Synthesis and
Reactions of Some New Thienopyrimidines, Phosphorus, Sulfur, and Silicon and the Related Elements, 178:4, 737-751, DOI:
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Phosphorus, Sulfur and Silicon, 2003, Vol. 178:737–751
C
Copyright 2003 Taylor & Francis
1042-6507/03 $12.00 + .00
DOI: 10.1080/10426500390198084
SYNTHESIS AND REACTIONS OF SOME NEW
THIENOPYRIMIDINES
Maisa I. Abdel Moneam, Ahmed A. Geies, Galal M. El-Naggar,
and Suliman M. Mussa
Assiut University, Assiut, Egypt
(Received May 10, 2002; accepted August 12, 2002)
4-Methyl-6-mercapto-2-phenylpyrimidine-5-carbonitrile (1) was re-
acted with different halo compounds, namely ethylchloroacetate, chloro-
acetone, bromoacetanilide, p-chlorobromoacetanilide, and p-methoxy
chloroacetanilide in ethanol in the presence of sodium acetate yielded
the corresponding S-alkylated derivatives (2a–e). The latter compounds
underwent cyclization into thienopyrimidines (4a–e) upon treatment
with sodium ethoxide in ethanol. The reaction of (4a) with hydrazine
hydrate led to the formation of 5-amino-4-methyl-2-phenylthieno[2,3-
d]pyrimidine-2-carbohydrazide (5). Compound (5) was reacted with a
variety of reagents to produce other new thienopyrimidines as well as
oxadiazolylthienopyrimidines (6, 11).
Thienopyrimidines and pyrimidothienopyrimidines have been subject
to chemical and biological studies due to their interesting pharma-
cological effects,1 which includes analgesic,2 antipyretic,3 and anti-
inflammatory4,5 properties. In view of the above activities, we report on
the synthesis of some new thienopyrimidines and pyrimidothienopy-
rimidines hoping to get compounds with high biological activity or
medicinal applications.
RESULTS AND DISCUSSION
The starting compound 4-methyl-6-mercapto-2-phenylpyrimidine-5-
carbonitrile (1) was prepared according to literature procedures.6 The
reaction of (1) with some halo-compounds, namely ethylchloroacetate,
Address correspondence to Maisa I. A. Moneam, Chemistry Department, Faculty of
Science, Assiut University, Assiut 71516, Egypt. E-mail: maisaabdelmoneam@hotmail.
com
737

738
M. I. A. Moneam et al.
chloroacetone, and N-arylchloroacetamide, on refluxing ethanol in the
presence of sodium acetate, afforded the S-alkylated derivatives (2a–e),
respectively, in excellent yields (Scheme 1). On the other hand, the reac-
tion of (1) with chloroacetonitrile under the above conditions yielded the
cyclized product 5-amino-4-methyl-2-phenylthieno[2,3-d]pyrimidine-6-
carbonitrile (3). Compounds (2a–e) underwent ring closure by re-
fluxing in ethanol containing sodium ethoxide to give thieno[2,3-d]-
pyrimidines (4a–e). Synthesis of thienopyrimidine derivatives (4a–e)
were achieved in one step by subjecting pyrimidine (1) to react with
above halo compounds in ethanol in the presence of sodium ethoxide
(Scheme 1).
SCHEME 1
Hydrazinolysis of ethyl 5-amino-4-methyl-2-phenylthieno-[2,3-d]-
pyrimidine-6-carboxylate (4a) with hydrazine hydrate in absolute
ethanol afforded the corresponding 6-carbohydrazide derivative (5).
The latter compound (5) was used as precursor intermediate to produce
other fused heterocyclic compounds. Refluxing 5 with carbon disulfide
in pyridine yielded oxadiazolyl derivative (6) instead of pyrimidothieno-
pyrimidine derivative (7). The formation of compond 6 was established

Synthesis and Reactions of Some New Thienopyrimidines
739
chemically by its reaction with dimethoxy tetrahydrofurane, to afford
pyrrolyl derivative 8. Compound 8 was prepared by another route from
compound 4a, which was converted into the corresponding pyrrolyl
derivative 9, followed by its hydrazinolysis to give carbohydrazide 10;
the latter compound was cyclized using CS2 in pyridine to afford com-
pound 8 which recently was reported by El-Kashef et al.7 Alkylation of
compound (6) with ethylchloroacetate in ethanol in presence of sodium
acetate gave the S-alkylated derivative (11).
Compound (5) was allowed to react with nitrous acid yielded the
corresponding carboazide (12), which upon boiling in dry xylene
underwent Curtius rearrangment to give 4-methyl-2-phenylimidazo
[40,50:4,5]thieno[2,3-d]pyrimidine-(6H,7H)one (13). Carbohydrazide
derivative 5 was reacted with acetylacetone in ethanol to produce pyra-
zolyl derivative 14. Also, compound 5 undergoes ring closure followed by
formaylation or N acylation upon treatment with formic acid or acetic
anhydride to afford compounds (15) and (16) respectively (Scheme 2).
Condensation of carbohydrazide derivative (5) with various aromatic
aldehydes in refluxing ethanol yielded the corresponding carbohydra-
zone derivatives (17a–c). Refluxing each of compounds (17a–c) with
carbon disulfide in pyridine for long time gave 9-methyl-7-phenyl-4-oxo-
2-thioxo-1,2,3-trihydro-pyrimido-[50,40:4,5]thieno[2,3-d]thiazine (18) in-
stead of the expected pyrimidothienopyrimidine (19).
We postulate that the mechanism of this reaction was proceeded as
reported previously8,9 as follows.
o-Amino ester (4a) was used as a starting material for synthesis of
some unreported new heterocyclic compounds, thus it’s reaction with
formamide and phenylisothiocyanate afforded the pyrimidothienopy-
rimidine derivatives (20, 21) respectively.
Saponification of (4a) using 10% sodium hydroxide gave the corre-
sponding sodium salt (22), which upon treatment with orthophospho-
ric acid, at room temperature, decarboxylation was occurred to give
4-methyl-2-phenylthieno[2,3-d] pyrimidine-5(6H)-one (23) (Scheme 4).
Thienopyrimidine-5-one derivative 23 was reacted with aromatic
aldehydes in ethanol in the presence of catalytic amount of piperidine
to give 6-aryledinethienopyrimidine-5-one 24a,b (Scheme 5). The lat-
ter compound was reacted with malononitrile in ethanol in the presence
of triethylamine to give pyranothienopyrimidine derivatives 25a,b. It
is worthy to mentioned that 25a,b also could be obtained by the re-
action of 21 with aryledinemalononitrile in ethanol in the presence of
triethylamines.
On the other hand, the active methylene compound 23 was sponta-
neously oxidized to produce the indigo like compound 26 when exposed

740
M. I. A. Moneam et al.
SCHEME 2
to air, which its suspension in ethanol was changed from white to red.
Also the dimmer compound 26 was produced when we try to react , -
unsaturated compounds 24a,b with hydrazines to synthesize pyrazolo
compound 27 (Scheme 5).
EXPERIMENTAL
Melting point are uncorrected and were measured on a Fisher-
John apparatus. IR spectra were recorded on a Shimaduz 470 IR

Synthesis and Reactions of Some New Thienopyrimidines
741
1
spectrophotometer using KBr discs, H-NMR spectra in a Varian EM
390 90 MHz NMR spectrometer using TMS as internal reference and
MS on Jeol JMS-600 apparatus. Elemental analysis were determined
on a Perkin-Elmer 240 C elemantel analyzer and the results were in
an acceptable range. All physical properties and spectral data of the
synthesized compounds are listed in Tables I and II.

742
M. I. A. Moneam et al.
4-Methyl-6-mercapto-2-phenylpyrimidine-
5-carbonitrile (1)
The above compound was prepared according to literature procedure.6
4-Methyl-6-substituted Mercapto-2-phenylpyrimidine-
5-carbonitrile (2a–e)
General Procedure
To a suspension of 1 (0.01 mmol) and sodium acetate (0.02 mmol) in
ethanol (100 ml), the respective halo-compound (0.01 mmol) was added.
The resulting mixture were refluxed for 3 h and then allowed to cool.
SCHEME 4

Synthesis and Reactions of Some New Thienopyrimidines
743
SCHEME 5
The precipitated product was collected by filtration, washed with water,
and recrystallized from ethanol to give 2a–e in the form of white fine
needles.
5-Amino-4-methyl-2-phenylthieno[2,3-d]pyrimidine-
6-carbonitrile (3)
A mixture of 1 (0.01 mmol) and chloroacetonitrile (0.01 mmol) in ethanol
(50 ml) containing sodium acetate (0.02 mmol) was refluxed for 1 h. The
solid product was formed during refluex was filtered off and recrystal-
lized from dioxane as yellow crystalls.
Cyclization of Compounds (2a–e); Synthesis
of Compounds (4a–e)
General Procedure: and Method A
A suspension of (2a–e) (0.05 mmol) in absolute ethanol (50 ml) con-
taining sodium (250 mg) was heated under reflux for 1 h. The products
was collected by filtration, washed thoroughly with water, and recrys-
tallized from ethanol to give 4a–e as yellow crystals.

744
M. I. A. Moneam et al.
TABLE I Physical Properties and Analytical Data of Compounds 2–23
Calculated/Found
Comp. no.
m.p. C
Yield %
83
Formula mol. wt
C
H
N
S
2a
124–126
C16H15N3O2S
313.38
C15H13N3OS
283.35
C20H16N4SO
360.34
C20H15ClN4OS
394.88
61.32
61.06
63.58
63.43
66.65
66.47
60.83
60.55
64.60
64.34
63.14
63.38
61.32
61.56
63.58
63.73
66.65
66.38
60.83
60.59
64.60
64.35
56.17
56.46
52.77
52.52
58.29
58.42
53.38
52.12
54.18
54.00
59.56
59.75
62.79
63.69
56.96
56.78
59.16
59.17
65.10
64.86
63.29
63.56
59.78
59.52
4.82
4.53
4.62
4.25
4.47
4.52
3.83
3.77
4.65
4.55
3.78
3.49
4.82
5.06
4.62
4.38
4.47
4.66
3.83
3.56
4.65
4.52
4.38
4.21
3.25
3.43
3.35
3.18
4.01
4.24
3.25
3.09
3.57
3.77
4.71
4.54
3.29
3.08
4.14
4.26
4.42
4.13
4.59
4.24
3.82
4.57
13.41
13.11
14.83
14.69
15.54
15.82
14.19
14.02
14.35
14.07
21.04
19.78
13.41
13.68
14.83
15.06
15.54
15.28
14.19
13.93
14.35
14.19
23.40
23.16
20.51
20.78
17.89
18.08
16.38
16.41
27.08
27.36
19.85
19.63
19.27
19.42
20.76
20.56
19.17
19.02
18.08
17.84
16.78
16.55
16.60
16.42
10.23
10.03
11.32
11.19
8.90
9.12
8.12
7.89
8.21
2b
2c
160
242–245
270
85
81
a
2d
82
2e
3
253–255
260
81
C
21H18N4O2S
390.46
8.32
70
C14H10N4S
266.32
12.04
11.86
10.23
10.46
11.32
11.53
8.90
8.62
8.12
7.86
8.21
4a
4b
4c
164–165
202
(76)
(77)
(73)
(76)
(74)
(86)
(64)
78
C
16H15N3O2S
313.38
C
15H13N3OS
283.35
240
C20H16N4SO
360.34
C20H15ClN4OS
394.88
C21H18N4O2S
390.46
a
4d
250
4e
5
230
8.11
235
C
14H13N5OS
299.35
10.71
10.52
18.78
19.05
16.83
17.12
15.00
15.22
10.33
10.02
11.36
11.04
8.82
8.99
9.51
9.34
8.78
8.52
8.28
8.03
7.68
6
>360
298
C
15H11N5OS2
341.41
8
C19H13N5OS2
391.47
11
12
13
14
15
16
17a
17b
210
(60)
(82)
(76)
(65)
(78)
(77)
(88)
(86)
(85)
C
19H17N5O3S2
427.50
170
C
14H10N6OS
310.34
>360
258–261
290
C14H10N4OS
282.32
C
19H17N5OS
363.12
C
C
16H11N5O2S
337.36
18H15N5O2S
365.41
330
290
C21H17N5OS
387.12
297–300
296
C
22H19N5O2S
417.48
7.44
7.60
7.33
b
17c
C21H16ClN5OS
421.5
(Continued on next page)

Synthesis and Reactions of Some New Thienopyrimidines
745
TABLE I Physical Properties and Analytical Data of Compounds 2–23
(Continued)
Calculated/Found
Comp. no.
m.p. C
Yield %
(68)
Formula mol. wt
C
H
N
S
18
>300
C15H9N3OS3
343.45
C15H10N4OS
294.06
C21H14N4OS2
402.49
C13H10N2OS
242.05
52.46
52.22
61.21
61.44
62.67
62.40
64.44
64.17
72.70
72.48
69.98
69.77
69.68
69.44
67.59
67.34
64.98
64.81
2.64
3.47
3.42
3.19
3.51
3.76
4.16
4.00
4.27
4.00
4.47
4.32
4.07
3.89
4.25
3.98
3.36
3.05
12.23
18.23
19.04
18.84
13.92
14.08
11.56
11.70
8.48
7.72
7.77
7.52
14.13
13.85
13.14
13.42
11.66
12.83
28.01
27.79
10.89
10.73
15.93
16.18
13.23
13.03
9.71
9.42
8.88
8.81
8.09
20
260
280
(62)
(50)
(63)
(73)
(77)
(71)
(83)
(65)
21
23
157–160
223
24a
24b
25a
25b
26
C
20H14N2OS
330.40
216
C21H16N2O2S
360.43
C23H16N4OS
396.47
291
7.87
7.52
7.27
13.35
13.09
279
C
24H18N4O2S
426.49
300
C26H16N4O2S2
480.07
aCl (Cal. 8.99, Found 8.72).
bCl (Cal. 8.40, Found 8.12).
Method B
A mixture of 1 (0.005 mmol) and the respective halo-compound in
absalute ethanol (50 ml) containing sodium (0.5 g) was refluxed for 1 h.
The solid was collected by filtration, washed with water, and recrys-
tallized from ethanol to give (4a–e). The products were identical with
those reported in method A.
5-Amino-4-methyl-2-phenylthieno[2,3-d]pyrimidine-
6-carbohydrazid (5)
A mixture of compound 4a (0.01 mmol) and hydrazine hydrate (3 ml) was
refluxed in ethanol (20 ml) for 4 h. The solid product which formed in hot
was filtered off and recrystallized from dioxane as pale yellow crystals.
5-Amino-6[4,5-Dihydro-5-thioxo-1,3,4-oxadiazol-3-yl]-
4-methyl-2-phenylthieno[2,3-d]pyrimidine (6)
A sample of compound 5 (0.5 g) and carbondisulfide (2 ml) in pyridine
(20 ml) was refluxed for 4 h in a steam bath. The solid was collected
and recrystallized from dioxane as yellow crystals.

746
M. I. A. Moneam et al.
TABLE II Spectroscopic Data of Compounds 2–26
Compd.
no.
IR ( cm 1)/1H-NMR (ppm)
1
1
1
2a
IR: = 2950 cm (CH-aliphatic), 2200 cm (C N) and 1720 cm (C O);
1HNMR (CDCl3): = 1.3 (t, 3H, CH3), 2.6 (s, 3H, CH3), 4.2 (s, 2H, CH2),
4.5 (q, 2H, SCH2), 7.7–8.5 (m, 5H, Ar-H)
1
1
1
2b
2c
2d
IR: = 2910 cm (CH-aliphatic), 2210 cm (C N) and 1715 cm (C O);
1HNMR (CDCl3): = 2.4 (s, 3H, CH3), 3.2 (s, 3H, OCH3) 3.5 (s, 2H, CH2),
7.8–8.5 (m, 5H, Ar-H)
1
1
1
IR: = 3250 cm (NH), 2200 cm (C N) and 1650 cm (C O): 1HNMR
(DMSO-d6): = 2.6 (s, 3H, CH3), 4.3 (s, 2H, CH2), 7.3–7.7 (m, 9H, Ar-H),
8.6 (s, 1H, NH)
1
1
1
IR: = 3240 cm (NH), 2205 cm (C N) and 1660 cm (C O); 1HNMR
(CDCl3): = 2.7 (s, 3H, CH3), 4.3 (s, 2H, CH2), 7.5–8.3 (m, 9H, Ar-H)
and 8.8 (s, 1H, NH)
1
1
1
2e
3
IR: = 3245 cm (NH), 2210 cm (C N) and 1655 cm (C O)
1 1 1
IR: = 3320–3220 cm (NH2), 2200 cm (C N) and 1590 cm (C N);
1HNMR (CF3CO2D): = 3.2 (s, 3H, CH3), 4.5 (s, 2H, NH2) and 7.7–8.4
(m, 5H, Ar-H)
1
1
4a
4b
IR: = 3450, 3350 cm 1(NH2), 3050 cm (CH-aliphatic), 1660 cm (C O)
and 1590 cm (C N); 1HNMR (DMSO-d6): = 1.1–1.4 (t, 3H, CH3 ethyl),
1
2.9 (s, 3H, CH3), 4.1–4.3 (q, 2H, CH2), 6.9 (s, 2H, NH2), and 7.3–8.3
(m, 5H, Ar-H)
1
1
1
IR: = 3400, 3300 cm (NH2), 1650 cm (C O) and 1600 cm (C N).
1HNMR (DMSO-d6): = 2.4 (s, 3H, CH3 pyrimidine), 3 (s, 3H,
C
O
CH3), 7.8 (s, 2H, NH2), and 7.7–8.7 (m, 5H, Ar-H)
1
1
1
4c
4d
4e
IR: = 3480 cm (NH), 3400–3350 cm (NH2), 1630 cm (C O),
1
1590 cm (C N). m/e = 359.76
1
1
1
IR: = 3475 cm (NH), 3400, 3300 cm (NH2), 1640 cm (C O),
1
1590 cm (C N)
1
1
1
IR: = 3450 cm (NH), 3400, 3300 cm (NH2) and 1630 cm (C O).
1HNMR (CDCl3): = 3 (s, 3H, CH3 pyrimidine), 3.8 (s, 3H, OCH3), 6.5
(s, 2H, NH2), 6.9–7.4 (m, 9H, Ar-H), 8.5 (s, 1H, NH)
1
1
5
IR: = 3400, 3300, 3200 cm (NH, NH2), 1640 cm (C
O ) and
1590 cm (C N); 1HNMR (DMSO-d6): = 3.2 (s, 3H, CH3), 4.6
1
(s, 2H, NH2), 7.2 (s, 2H, NH2), 7.6–8.7 (m, 5H, Ar-H), and 9.5 (s, 1H, NH)
1
1
1
6
8
IR: = 3400, 3300 cm (NH2), 2900 cm (SH), 1620 cm (C N)
1 1
IR: = 3300 cm (NH), 1600 cm (C N). 1HNMR (CDCl3): = 2.7
(s, 3H, CH3 pyrimidine), 6.6 (m, 2H, pyrrolyl-H), 6.8 (m, 2H, pyrrolyl-H),
8.0–8.3 (m, 9H, Ar-H), 13.0 (s, 1H, NH)
1
1
1
11
IR: = 3450, 3350 cm (NH2), 2950 cm (CH aliphatic) and 1610 cm
(C N). 1HNMR (CDCl3): = 1.2–1.3 (t, 3H, CH3), 2.9 (s, 3H, CH3), 4.1
(q, 2H, CH2), 4.6 (s, 2H, SCH2), 6.1 (s, 2H, NH2), 7.5–8.5 (m, 5H, Ar-H)
1
1
1
12
13
IR: = 3500, 3400 cm (NH2), 2125 cm (N3), 1650 cm (C O) and
1
1590 cm (C N)
1
1
1
IR: = 3200 cm (NH), 1680 cm (C O) and 1590 cm (C N). 1HNMR
(DMSO-d6): = 2.7 (s, 3H, CH3), 7.5–8.4 (m, 5H, Ar-H), 11.3 (s, 2H, 2NH)
(Continued on next page)

Synthesis and Reactions of Some New Thienopyrimidines
747
TABLE II Spectroscopic Data of Compounds 2–26 (Continued)
Compd.
no.
IR ( cm 1)/1H-NMR (ppm)
1
1
1
14
IR: = 3450, 3350 cm (NH2), 1680 cm (C O) and 1620 cm (C N).
1HNMR (CDCl3): = 2.1, 2.3 (2s, 6H, 2CH3), 2.6 (s, 3H, CH3), 5.8
(s, 2H, NH2) and 7.24–7.26 (m, 6H, Ar-H, CH pyrazoline)
1
1
1
15
IR: = 3450 cm (NH), 1710 cm 1, 1670 cm (2 C O) and 1590 cm
(C N). 1HNMR (DMSO-d6): = 2.4 (s, 3H, CH3), 7.5–8.4 (m, 5H, Ar-H),
8.5 (s, 1H, CH-pyrimidine), 8.6–8.7 (d, 1H, CHO), 8.8 (d, 1H, NH)
1
1
1
16
IR: = 3250 cm (NH), 1710, 1670 cm (2 C O) and 1590 cm (C N).
1HNMR (DMSO-d6): = 2.3 (s, 3H, CH3), 2.5 (s, 3H, CH3), 2.8 (s, 3H, CH3),
7.49–7.54, 8.4–8.42 (2m, 5H, Ar-H), 11.34 (s, 1H, NH)
1
1
1
17a
17b
IR: = 3480, 3370, 3300 cm (NH, NH2), 1640 cm (C O) and 1595 cm
(C N). 1HNMR (DMSO-d6): = 2.9 (s, 3H, CH3), 7.4 (s, 2H, NH2), 7.9–8.6
(m, 6H, 5 Ar-H, N CH), 11.7 (s, 1H, NH)
1
1
1
IR: = 3500, 3400, 3300 cm (NH, NH2), 1645 cm (C O) and 1595 cm
(C N). 1HNMR (DMSO-d6): = 2.9 (s, 3H, CH3), 3.8 (s, 3H, CH3),
7.07–7.72 (2d, 4H, Ar-H), 7.5–8.4 (m, 5H, Ar-H), 7.6 (s, 2H, NH2)
and 8 (s, 1H, CH N)
17c
18
IR: = 3500–3300 (NH, NH2), 1640 (C O), 1590 (C N)
1
1
IR: = 3310 cm (NH), 1680 cm (C O) and 1600 (C N). 1HNMR
(DMSO-d6): = 2.7 (s, 3H, CH3), 7.3–8.3 (m, 5H, Ar-H), 9.5 (s, 1H, NH)
1
1
20
IR: = 3350 cm (NH) and 1660 cm (C O). 1HNMR (CF3CO2D): = 2.7
(s, 3H, CH3), 7.7–8.0, 8.3–8.5 (2m, 5H, Ar-H) and 8.8 (s, 1H, N CH)
IR: = 3400 (NH), 1680 (C O), 1600 (C N). 1HNMR (CF3CO2D) = 3.3
(s, 3H, CH3) and 7.5–8.6 (m, 10 H aromatic)
21
1
1
23
IR: = 1680 cm (C O) and 1600 cm (C N) (CDCl3) 2.8 (s, 3H, CH3),
3.8 (s, 2H, CH2), 7.3–8.5 (2m, 5H, aromatic)
1
1
24a
24b
1665 cm (C O) and 1600 cm (C N). 1HNMR (DMSO-d6): = 2.8 (s, 3H,
CH3), 7.5–7.7 (m, 5H, aromatic), 7.81–8.0 (2d, 4H, Ar-H) and 8.2 (s, 1H, CH)
1
1
IR: = 1660 cm (C O) and 1590 cm (C N). 1HNMR (DMSO-d6):
= 2.9 (s, 3H, CH3), 3.5 (s, 3H, OCH3), 7.5–7.6 (m, 5H, Ar-H), 7.81,
7.83, 8.48, 850 (2d, 4H, Ar-H) and 8 (s, 1H, CH)
1
1
1
25a
25b
26
IR: = 3400, 3300 cm (NH2), 2200 cm (C N) and 1600 cm (C N).
1HNMR (DMSO-d6) = 2.9 (S, 3H, CH3), 5.1 (s, 1H, CH pyrane), 6.9
(s, 2H, NH2), 7.2–7.7 and 8.0–8.5 (2m, 9H, Ar-H)
1
1
1
IR: = 3400, 3300 cm (NH2), 2200 cm (C N) and 1590 cm (C N).
1HNMR (DMSO-d6): = 2.9 (s, 3H, CH3), 3.4 (s, 3H, OCH3), 4.9
(s, 1H, CH pyrane), 6.8 (s, 2H, NH2), and 7.0–7.6, 8.3–8.5 (2m, 10H, Ar-H)
1
1
IR: = 1680 cm (C O), 1600 cm (C N). 1HNMR (CF3CO2D):
= 2.35 (s, 6H, 2CH3) and 7.3–7.5, (m, 10H, Ar-H). m/e = 479.78
6-[4,5-Dihydro-5-thioxo-1,3,4-oxadiazol-3-yl]-4-methyl-
2-phenyl-5-[1-pyrrolyl]-thieno[2,3-d]pyrimidine (8)
A mixture of compound 5 (0.01 mmol) and dimethoxytetrahydrofuran
(0.01 mmol) in acetic acid (20 ml) was refluxed for 1 h, allowed to cool,

748
M. I. A. Moneam et al.
and poured into cold water (100 ml). The solid product was collected,
washed several times with water, and recrystallized from ethanol as
white crystals.
Ethyl 4-Methyl-2-phenyl-5-[pyrrol-1-yl]thieno[2,3-d]-
pyrimidine-6-carboxylate (9)
Title compound was prepared according to literature procedure, m.p.
176 C; Lit.7 m.p. 175–176 C.
4-Methyl-2-pheny-5-[pyrrol-1-yl]thieno[2,3-d]pyrimidine-
6-carbohydrazid (10)
Title compound was prepared according to literature procedure, m.p.
221 C; Lit.7 m.p. 220–221 C.
5-Amino-6[2-ethoxycarbonylmethylmercaptooxadiazol-
5-yl]-4-methyl-2-phenylthieno-[2,3-d] pyrimidine (11)
A mixture of compound 6 (0.01 mmol), ethylchloroacetate (0.01 mmol)
and sodium acetate (0.012 mmol) in ethanol (30 ml) was heated under
reflux for 3 h, and allowed to cool to room temperature. The solid product
was collected by filtration, washed well with water, and recrystallized
from ethanol as yellow crystals.
5-Amino-4-methyl-2-phenylthieno[2,3-d]pyrimidine-
6-carboazide (12)
To a cooled solution of compound 5 (0.01 mmol) in glacial acetic acid
(20 ml), sodium nitrite solution (0.69 g in 5 ml H2O) was added dropwise
with stirring. The stirring was continued for additional 2 h, then the
reaction mixture was allowed to stand 5 h. The solid product separated
was filtered off, washed severel times with water, and air dried to give
pale yellow crystals. This compound was subjected to the next step
without further purefication.
4-Methyl-2-phenylimidazo[40,50:4,5]thieno[2,3-d]-
pyrimidine-(6H,7H)-one (13)
A sample of compound 10 (0.5 g) in dry xylene (10 ml) was heated under
reflux for 3 h, then allowed to cool to the room temperature. The solid
product was collected and recrystallized from dioxane into pale brown
crystals.

Synthesis and Reactions of Some New Thienopyrimidines
749
5-Amino-6[carbonyl-30,50-dimethylpyrazol]-4-methyl-
2-phenylthieno-[2,3-d]pyrimidine (14)
A mixture of hydrazide 5 (0.01 mmol) and acetyl acetone (0.012 mmol)
in ethanol (40 ml) was refluxed for 3 h, then allowed to cool. The solid
product was collected and recrystallized from ethanol as yellow needles.
7-N-Formylamino-4-methyl-2-phenylpyrimido-
[40,50:4,5]thieno[2,3-d]-pyrimidine 8 (7H) one (15)
A sample of compound 5 (0.5 g) in formaic acid (5 ml) was refluxed for
5 h, then allowed to cool to the room temperature. The solid product
was collected and recrystallized from dioxane as pale yellow crystals.
7-N-Acetylamino-4,6-dimethyl-2-phenylpyrimido-
[40,50:4,5]thieno-[2,3-d]pyrimidine-8(7H) one (16)
A sample of compound 5 (0.5 g) was refluxed in acetic anhydride (10 ml)
for 2 h, then allowed to cool and poured into cold water. The solid product
was collected and recrystallized from dioxane as pale yellow crystals.
6-Aryledine carbohydrazone-5-amino-4-methyl-
2-phenylthieno[2,3-d]-pyrimidine (17a–c)
General Procedure
A mixture of thienopyrimidine carbohydrazide 5 (0.01 mmol) and
appropriate aromatic aldehyde (0.01 mmol) in ethanol (30 ml) was re-
fluxed for 4 h, then allowed to cool to the room temperature. The solid
product was collected and recrystallized from dioxane.
9-Methyl-7-phenyl-1,2,4-trihydro-4-oxo-
2-thioxopyrimido[40,50:4,5][1,3]thiazine (18)
A mixture of each 6-aryledinecarbohydrazone derivatives (17a–c) (2 g)
and carbondisulfide (2 ml) in pyridine (20 ml) was heated on water bath
for 50 h, then allowed to cool to room temperature. The solid product
was collected and recrystallized from dioxane as yellow crystals.
4-Methyl-2-phenylpyrimido[40,50:4,5]thieno[2,3-d]-
pyrimidine 8(7H)-one (20)
A sample of compound 4a (1 g) in formamide (10 ml) was refluxed for
3 h. The solid product which separated from the hot mixture was filtered
off and recrystallized from dioxane as pale green crystals.

750
M. I. A. Moneam et al.
2,7-Diphenyl-5,6,7,8-tetrahydro-8-oxo-
4-methylpyrimido[40,50:4,5]-thieno[2,3-d]-pyrimidine-
6-thion (21)
A mixture of compound 4a (0.01 mmol) and phenylisothiocyanate
(0.01 mmol) in 30 ml pyridine was refluxed for 10 h, then allowed to
cool to room temperature. The solid product was collected by filtration
and recrystallized from D.M.F as yellow crystals.
4-Methyl-2-phenylthieno[2,3-d]pyrimidine-5-one (23)
A mixture of compound (22) (0.01 mmol) and o-phosphoric acid (10 ml)
was stirred at room temperature for 3 h, then cooled and neutralized
by ammonium hydroxide the white precipitate was filtered off as white
crystalls. This compound used without crystallization.
4-Methyl-3-phenyl-6-aryledinethieno[2,3-d]pyrimidine-
5-one (24a,b)
General Procedure
A mixture of 23 (0.01 mmol) and the respective aromatic alde-
hyde (0.01 mmol) in ethanol (50 ml) containing catalytic amount of
piperidine was refluxed for 3 h. The solid product, which formed af-
ter cooling, was filtered off and recrystallized from ethanol as yellow
crystalls.
6-Amino-8-aryl-7-cyano-4-methyl-2-phenylpyrano-
[20,30:4,5]thieno[2,3-d]pyrimidine (25a,b)
Method A
A mixture of compound (24a,b) (0.01 mmol) and malononitrile
(0.01 mmol) in ethanol (50 ml) containing triethylamine was refluxed
for 4 h. The precipitated thus formed during reflux was collected by
filteration and crystallized from dioxane as yellow crystalls.
Method B
A mixture of 23 (0.01 mmol) and aryledinemalononitrile (0.01 mmol)
in ethanol (50 ml) containing triethylamine was refluxed for 5 h.
The preciptated thus formed during refluex was collected by filtra-
tion, washed well with ethanol, and crystallized from dioxane as
yellow crystalls. The products were identical with those reported in
method A.

Synthesis and Reactions of Some New Thienopyrimidines
751
4,40-Dimethyl-2,20-diphenyl[2,20]bi[thieno[2,3-d]
pyrimidinylidene-3,30-dione (26)
Method A
A sample of compound 23 (0.5 gm) was heated in ethanol (20 ml)
until dissolved, then allowed to exposed to atmospheric air for 2 days.
The solution was turned into red and the solid product was collected
and identified as a dimmer 26 in 65% yield
Method B
A mixture of compound 24a or 24b (0.01 mmol) and phenyl hydrazine
(0.01 mmol) in ethanol (20 ml) was heated under reflux for 3 h. The red
solid crystals which was separated on hot was identified as a dimmer
26 in 55% yield. The mother liquer was evaporated and the residue was
identified as arylidene phenylhydrazone.
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