Cyanothioacetamide and its derivatives in heterocyclic chemistry: Synthesis of some new thioxopyridine, thienopyridine, and pyridothienopyrimidine derivatives

Article abstract of DOI:10.1080/10426500802237143

A number of thieno[2,3-b]pyridines (9-13) and pyridothienopyrimidines (14-16) were synthesized via the reaction of the dihydrothioxopyridine derivatives (7a,b), obtained by the action of ethyl acetoacetate on arylidine cyanothioacetamide 4, with halogenat

Full text of DOI:10.1080/10426500802237143

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Cyanothioacetamide and Its
Derivatives in Heterocyclic
Chemistry: Synthesis of
Some New Thioxopyridine,
Thienopyridine, and
Pyridothienopyrimidine
Derivatives
Nada M. Abunada a , Ali K. K. El-Louh b & Ismaeel S.
Al-Zaeem a
a Department of Chemistry, Faculty of Applied
Science, Al-Aqsa University, Gaza, Palestine
b Department of Chemistry, Faculty of Science, Al-
Azhar University-Gaza, Gaza, Palestine
Published online: 19 Feb 2009.
To cite this article: Nada M. Abunada , Ali K. K. El-Louh & Ismaeel S. Al-Zaeem
(2009) Cyanothioacetamide and Its Derivatives in Heterocyclic Chemistry: Synthesis of
Some New Thioxopyridine, Thienopyridine, and Pyridothienopyrimidine Derivatives,
Phosphorus, Sulfur, and Silicon and the Related Elements, 184:3, 591-601, DOI:
10.1080/10426500802237143
To link to this article: http://dx.doi.org/10.1080/10426500802237143
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Phosphorus, Sulfur, and Silicon, 184:591–601, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802237143
Cyanothioacetamide and Its Derivatives in Heterocyclic
Chemistry: Synthesis of Some New Thioxopyridine,
Thienopyridine, and Pyridothienopyrimidine Derivatives
Nada M. Abunada,1 Ali K. K. El-Louh,2
and Ismaeel S. Al-Zaeem1
1Department of Chemistry, Faculty of Applied Science, Al-Aqsa
University, Gaza, Palestine
2Department of Chemistry, Faculty of Science, Al-Azhar
University–Gaza, Gaza, Palestine
A number of thieno[2,3-b]pyridines (9–13) and pyridothienopyrimidines (14–16)
were synthesized via the reaction of the dihydrothioxopyridine derivatives (7a,b),
obtained by the action of ethyl acetoacetate on arylidine cyanothioacetamide 4, with
halogenated compounds 8a–f.
Keywords Cyanothioacetamide; dihydrothioxopyridine; pyridothienopyrimidine;
thienopyridine
INTRODUCTION
Much effort has been done in the synthesis of heterocyclic compounds
using cyanothioacetamide and its derivatives.1–10 Many thienopyridine
derivatives obtained by this route have been evaluated to possess good
antibacterial,11–13 antihypertensive,14 antimicrobial,15 analgesic, and
anti-inflamatory16–18 activities, and to act as gonadotropin-releasing
hormone antagonists.17,18 Pyridothienopyrimidines are known to ex-
hibit analgesic and anti-inflammatory activities.19 These findings along
with our interest in the synthesis of thienopyridines5,20 via the reaction
of cyanoacetamide with aldehydes and dicarbonyl derivatives prompted
us to attempt the synthesis of new representatives of these heterocycles
using cyanothioacetamide with new aromatic aldehyde derivatives.
Received 14 April 2008; accepted 29 May 2008.
Address correspondence to Nada M. Abunada, Department of Chemistry, Fac-
ulty of Applied Science, Al-Aqsa University, P. O. Box 4051, Gaza, Palestine. E-mail:
nadanadannrs@yahoo.com
591

592
N. M. Abunada et al.
RESULTS AND DISCUSSION
Here we report the synthesis of some new thienopyridines and pyri-
dothienopyrimidines beginning with dihydrothioxopyridine derivatives
7a,b. Compounds 7a,b were prepared in a one-pot reaction of cyanoth-
ioacetamide 1, aromatic aldehydes 2a,b, and ethyl acetoacetate 3 under
reflux conditions in dioxane containing a catalytic amount of piperi-
dine, or from the reaction of the arylidene cyanothioacetamides 4a,b
with ethyl acetate under the same reaction conditions. The structures
of the compounds 7a,b result from correct analytical and spectroscopic
data (Tables I and II). Compounds 521 or 65 were not detected among
the reaction products (Scheme 1).
SCHEME 1

Cyanothioacetamide in Heterocyclic Synthesis
593
Treatment of compounds 7a,b with halogenated compounds 8a–f in
basic ethanolic solution under reflux conditions gave the thieno[2,3-
b]pyridine derivatives 9a,b through 13a,b (Scheme 2). The structures
of compounds 9–13 were assigned on the basis of elemental analy-
ses and spectroscopic data. The IR spectra of all compounds reveal
the absence of NH and CN absorption bands, typical for 7a,b, and
showabsorption bands of NH2 in addition to new bands corresponding
to the introduced new substituents. The 1H NMR spectrum of 12a (Ta-
ble I) shows a new broad signal at δ = 5.75 ppm, which is assigned
to the NH2 protons. The products from the reaction of 7a,b with 8e
1
proved to be identical in all respects (melting points, IR, H, and 13C
NMR, mass spectra) with those obtained from 7a,b and 8f.
SCHEME 2
The structures of compounds 9a,b and 10a,b were further confirmed
by the following reactions: treatment of compounds 9a,b or 10a,b with
formic acid, of 9a,b with formamide, and of 10a,b with acetic anhydride
at reflux conditions gave the corresponding pyrido[3,2:4,5]thieno[3,2-
d]pyrimidine derivatives 14a,b through 16a,b, respectively. The struc-
tures of 14–16 are supported by the elemental analyses and the spec-
troscopic data (Tables I and II). The IR spectrum of 16b exhibits an

594
N. M. Abunada et al.
TABLE I Physical Data and Elemental Analyses for Compounds 7,
9–16
Analysis Calcd./Found (%)
M.p. (◦C)
(Color)
Molecular Formula
MS, m+/z
Comp.
Yield (%)
61
C
H
N
S
7a
245–7
Yellow
226–8
Yellow
258–60
Yellow
248–50
Yellow
264–6
Yellow
226–4
Yellow
158–60
Yellow
201–3
Yellow
161–3
Yellow
156–8
Yellow
174–6
Yellow
189–91
Orange
288–90
Yellow
268–70
Yellow
244–6
Green
221–3
Green
318–20
White
287–9
White
C17H14N2O4S
356
59.57
59.70
60.03
60.12
59.83
59.69
60.44
60.35
57.13
57.30
57.82
57.69
65.21
65.16
65.53
65.49
58.87
58.69
59.45
59.39
60.29
60.18
60.86
60.78
58.67
58.55
59.28
59.26
58.81
58.66
59.42
59.34
59.57
59.48
60.12
60.08
4.11
4.20
5.06
4.96
3.96
3.78
4.81
4.78
4.29
4.18
5.09
4.97
4.37
4.29
5.07
5.04
4.70
4.65
5.44
5.36
4.55
4.47
5.35
5.26
3.69
3.58
4.50
4.48
3.94
3.78
4.75
4.57
4.04
3.92
4.81
4.77
8.17
8.10
7.81
9.33
9.24
8.92
8.87
8.39
8.31
8.05
8.12
8.01
7.97
7.70
7.68
6.95
6.91
6.71
6.67
7.46
7.38
7.20
7.24
8.03
8.08
7.72
7.69
7.81
7.78
7.52
7.48
7.83
7.75
7.53
7.50
7.55
7.51
7.28
7.19
7b
70
89
78
93
88
89
90
68
73
61
63
92
78
57
54
55
50
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
18H18N2O4S
372
19H15N3O4S
381
20H19N3O4S
397
19H17N3O5S
399
20H21N3O5S
415
25H20N2O5S
460
26H24N2O5S
476
21H20N2O6S
428
22H24N2O6S
444
20H18N2O5S
398
21H22N2O5S
414
20H15N3O5S
409
21H19N3O5S
425
20H16N4O4S
408
21H20N4O4S
424
21H17N3O5S
423
7.78
9a
11.02
10.89
10.57
10.46
10.52
10.38
10.11
10.07
6.08
6.05
5.88
5.82
6.54
6.48
6.30
6.24
7.03
6.97
6.76
6.69
9b
10a
10b
11a
11b
12a
12b
13a
13b
14a
14b
15a
15b
16a
16b
10.26
10.19
9.88
9.80
13.72
13.67
13.20
13.22
9.92
9.86
9.56
9.50
22H21N3O5S
439
absorption band at 3160 cm−1, which can be assigned to the NH group.
1
The H NMR spectrum displays a new singlet at δ = 2.14 ppm. The
mass spectra of all new compounds were in accord with the assigned
structures.

Cyanothioacetamide in Heterocyclic Synthesis
595
TABLE II IR and NMR Spectroscopic Data of Compounds 7, 9–16
IR [KBr, cm−1
]
1H NMR [δ, ppm]
13C NMR [δ, ppm]
7a
3458 (NH), 2226
(CN), 1708 (CO)
0.94 (t, J = 7.2 Hz, 3H,
COOCH2CH3), 3.28 (s,
3H, CH3 pyridine), 3.93
(q, J = 7.2 Hz, 2H,
COOCH2CH3), 6.10 (s,
2H, (OCH2O), 6.78-7.03
(m, 3H, arom-H), 13.9
(s, br, 1H, NH)
178.6 (C=S), 164.6 (CO
ester), 154.5, 152.6, 148.6,
147.2, 128.7, 121.9, 118.9,
116.4, 114.3, 108.5, 108.2
(C-arom, CN), 101.8
(OCH2O), 61.5 (CH2CH3),
18.0 (CH3 pyridine), 13.5
(CH2CH3)
7b
3446 (NH), 2227
(CN), 1708 (CO
ester)
0.96 (t, J = 7.2 Hz, 3H,
COOCH2CH3), 3.15 (s,
3H, CH3 pyridine), 3.77
(s, 3H, OCH3), 3.82 (s,
3H, OCH3), 3.93 (q, J =
7.2 Hz, 2H,
178.5 (C=S), 163.8 (CO
ester), 154.4, 152.5, 148.6,
147.3, 128.8, 122.0, 119.1,
116.4, 114.3, 108.5, 108.2
(C-arom, CN), 61.5
(CH2CH3), 55.7 (OCH3),
55.6 (OCH3), 18.1 (CH3
pyridine), 13.5 (CH2CH3)
COOCH2CH3),
6.89–7.12 (m, 3H,
arom-H), 14.10 (s, br,
1H, NH)
9a
9b
3465, 3342 (NH2),
2197 (CN), 1724
(CO ester)
0.98 (t, J = 7.2 Hz, 3H,
COOCH2CH3), 2.46 (s,
3H, CH3 pyridine), 4.05
(q, J = 7.2 Hz, 2H,
COOCH2CH3), 5.49 (s,
2H, NH2), 6.89–7.13
(m, 3H, arom-H)
166.2 (CO ester), 159.6,
157.8, 148.8, 148.7, 145.3,
141.2, 137.9, 136.2, 127.1,
126.4, 124.7, 115.4, 109.6,
108.7 (C- arom, CN), 101.7
(OCH2O), 62.0 (CH2CH3),
24.3 (CH3 pyridine), 13.9
(CH2CH3)
166.2 (CO ester), 159.6,
157.6, 148.6, 148.0, 145.4,
140.9, 138.1, 136.4, 127.2,
126.5, 124.9, 115.4, 109.5,
108.7 (C- arom, CN), 62.0
(CH2CH3), 55.7 (OCH3),
55.6 (OCH3), 18.4 (CH3
pyridine), 13.9 (CH2CH3)
3469, 3346 (NH2),
2198 (CN), 1728
(CO ester)
0.92 (t, J = 7.2 Hz, 3H,
COOCH2CH3), 2.58 (s,
3H, CH3 pyridine), 3.75
(s, 3H, OCH3), 3.83 (s,
3H, OCH3), 4.01 (q, J =
7.2 Hz, 2H,
COOCH2CH3), 5.57 (s,
2H, NH2), 6.90–7.14
(m, 3H, arom-H)
10a 3451, 3325, 3267,
3160 (NH2),
0.98 (t, J = 7.2 Hz, 3H,
COOCH2CH3), 2.48 (s,
3H, CH3 pyridine), 4.06
(q, J = 7.2 Hz, 2H,
167.0 (CO amide), 165.3 (CO
ester), 159.4, 153.6, 148.4,
147.6, 146.0, 141.9, 134.4,
126.5, 123.1, 120.4, 109.6,
108.6, 97.9 (C-arom), 101.3
(OCH2O), 62.5 (CH2CH3),
24.3 (CH3 pyridine), 13.9
(CH2CH3)
1724 (CO ester),
1658 (CO amide)
COOCH2CH3), 5.82 (s,
2H, NH2), 6.13 (s, 2H,
OCH2O), 6.79–6.95 (m,
3H, arom-H), 7.16 (s,
br, 2H, NH2)
(Continued on next page)

596
N. M. Abunada et al.
TABLE II IR and NMR Spectroscopic Data of Compounds 7, 9–16
(Continued)
IR [KBr, cm−1
]
1H NMR [δ, ppm]
13C NMR [δ, ppm]
10b
3480, 3428, 3328,
3266 (NH2),
1733 (CO ester),
1658 (CO amide)
0.98 (t, J = 7.2 Hz, 3H,
COOCH2CH3), 2.48 (s,
3H, CH3 pyridine), 3.75
(s, 3H, OCH3), 3.83 (s,
3H, OCH3), 4.06 (q, J =
7.2 Hz, 2H,
COOCH2CH3), 5.82 (s,
2H, NH2), 6.78-7.05 (m,
3H, arom-H), 7.14 (s,
br, 2H, NH2)
166.8 (CO amide), 165.3
(CO ester), 159.4, 153.7,
148.3, 147.5, 146.1,
141.6, 134.4, 126.8,
123.5, 119.6, 109.9,
108.6, 97.9 (C arom),
55.8 (OCH3), 55.7
(OCH3), 62.5 (CH2CH3),
24.3 (CH3 pyridine), 13.9
(CH2CH3)
11a
3464, 3320 (NH2),
1728 (CO ester)
0.98 (t, J = 7.2 Hz, 3H,
COOCH2CH3), 2.58 (s,
3H, CH3 pyridine), 4.06
(q, J = 7.2 Hz, 2H,
196.5 (CO ketone), 166.2
(CO ester), 160.2, 156.4,
148.8, 148.5, 146.3,
141.1, 135.6, 133.7,
132.7, 128.3, 128.0,
126.5, 125.7, 120.4,
118.3, 109.3, 107.0
(C-arom), 101.8
COOCH2CH3), 6.15 (s,
2H, OCH2O), 6.85–7.76
(m, 10H, arom-H, NH2)
(OCH2O), 62.1
(CH2CH3), 24.3 (CH3
pyridine), 13.8 (CH2CH3)
195.8 (CO ketone), 165.6
(CO ester), 160.0, 156.2,
148.8, 148.6, 146.1,
141.2, 137.8, 133.7,
132.9, 128.4, 127.9,
126.2, 125.8, 120.3,
118.4, 109.2.2, 108.0
(C-arom), 61.9
11b
3471, 3325 (NH2),
1731 (CO ester)
0.93 (t, J = 7.2 Hz, 3H,
COOCH2CH3), 2.57 (s,
3H, CH3 pyridine), 3.77
(s, 3H, OCH3), 3.84 (s,
3H, OCH3), 4.03 (q, J =
7.2 Hz, 2H,
COOCH2CH3),
6.90-7.74 (m, 10H,
arom-H, NH2)
(CH2CH3), 55.9 (OCH3),
55.2 (OCH3), 24.3 (CH3
pyridine), 13.8 (CH2CH3)
165.3 (CO ester), 164.2 (CO
ester), 159.8, 154.3,
148.4, 147.9, 147.8,
142.4, 134.5, 126.2,
123.0, 119.6, 109.5,
108.8, 94.5 (C-arom),
101.6 (OCH2O), 62.1
(CH2CH3), 61.8
12a
3467, 3345 (NH2),
1729, 1669 (CO
ester)
0.96 (t, J = 7.2 Hz, 3H,
COOCH2CH3), 1.24 (t,
J = 6.9 Hz, 3H,
COOCH2CH3), 2.56 (s,
3H, CH3 pyridine), 4.06
(q, J = 7.2 Hz, 2H,
COOCH2CH3), 4.23 (q,
J = 6.9 Hz, 2H,
COOCH2CH3), 6.12 (s,
2H, OCH2O), 5.75 (s,
br, 2H, NH2), 6.81-7.08
(m, 3H, arom-H)
(CH2CH3), 24.3
(CH3pyridine), 14.4
(CH2CH3), 13.8
(CH2CH3)
(Continued on next page)

Cyanothioacetamide in Heterocyclic Synthesis
597
TABLE II IR and NMR Spectroscopic Data of Compounds 7, 9–16
(Continued)
IR [KBr, cm−1
]
1H NMR [δ, ppm]
13C NMR [δ, ppm]
12b
3460, 3340 (NH2),
1735, 1690 (two
CO ester)
1.01 (t, J = 7.2 Hz, 3H,
COOCH2CH3), 1.23
(t, J = 6.9 Hz, 3H,
COOCH2CH3), 2.55
(s, 3H, CH3 pyridine),
3.77 (s, 3H, OCH3) ,
3.83 (s, 3H, OCH3),
4.04 (q, J = 7.2 Hz,
2H, COOCH2CH3),
4.22 (q, J = 6.9 Hz,
COOCH2CH3), 5.77
(s, br, 2H, NH2),
166.1 (CO ester), 164.5 (CO
ester), 159.8, 156.3,
148.5, 147.8, 147.7,
142.8, 136.7, 126.8,
125.6, 119.5, 108.9,
108.7, 94.6 (C-arom),
62.1 (CH2CH3), 61.8
(CH2CH3), 55.2 (OCH3),
55.8 (OCH3), 24.3 (CH3
pyridine), 14.4
(CH2CH3), 13.8
(CH2CH3)
6.84-7.09 (m, 3H,
arom-H)
13a
3472, 3312 (NH2),
1727 (CO ester)
0.96 (t, J = 7.2 Hz, 3H,
COOCH2CH3), 2.31
(s, 3H, COCH3), 2.55
(s, 3H, CH3 pyridine),
4.05 (q, J = 7.2 Hz,
2H, COOCH2CH3),
6.11 (s, 2H, OCH2O),
6.41 (s, br, 2H, NH2),
6.80–7.08 (m, 3H,
arom-H)
0.98 (t, J = 7.2 Hz, 3H,
COOCH2CH3), 2.33
(s, 3H, COCH3), 2.54
(s, 3H, CH3 pyridine),
4.06 (q, J = 7.2 Hz,
2H, COOCH2CH3),
6.11 (s, 2H, OCH2O),
6.42 (s, br, 2H, NH2),
6.83–7.09 (m, 3H,
arom-H)
191.7 (CO ketone), 165.9
(CO ester), 159.7, 157.0,
149.1, 148.9, 145.1,
143.2, 134.5, 126.4,
123.8, 119.4, 109.4,
108.8, 104.8 (C-arom),
101.0 (OCH2O), 61.6
(CH2CH3), 29.2 (CH3
acetyl), 24.3 (CH3
pyridine), 13.8 (CH2CH3)
192.2 (CO acetyl), 166.2
(CO ester), 159.3, 155.2,
148.6, 148.2, 145.9,
143.1, 134.6, 126.0,
122.9, 119.6, 109.3,
108.9, 104.7 (C-arom),
61.6 (CH2CH3), 55.2
(OCH3), 55.9 (OCH3),
29.0 (CH3 acetyl), 24.3
(CH3 pyridine), 13.8
(CH2CH3)
13b
3465, 3310 (NH2),
1725 (CO ester)
14a
3159 (NH), 1726
(CO ester), 1669
(CO lactam)
0.99 (t, J = 7.2 Hz, 3H,
COOCH2CH3), 2.62
(s, 3H, CH3 pyridine),
4.07 (q, J = 7.2 Hz,
2H, COOCH2CH3),
6.13 (s, 2H, OCH2O),
6.75–6.98 (m, 3H,
166.4 (CO ester), 163.5 (CO
lactam), 158.6, 157.9,
154.8, 148.9, 147.9,
143.0, 138.5, 135.9,
127.1, 124.5, 119.5,
113.2, 108.3, 106.6
(C-arom), 101.2
arom-H), 8.09 (s, 1H,
CH pyrimidine),
12.34 (s, br, 1H, NH)
(OCH2O), 61.3
(CH2CH3), 24.3 (CH3
pyridine), 13.9 (CH2CH3)
(Continued on next page)

598
N. M. Abunada et al.
TABLE II IR and NMR Spectroscopic Data of Compounds 7, 9–16
(Continued)
IR [KBr, cm−1
]
1H NMR [δ, ppm]
13C NMR [δ, ppm]
14b
3166 (NH), 1726
(CO ester), 1645
(CO lactam)
0.96 (t, J = 7.2 Hz, 3H,
COOCH2CH3), 2.62
(s, 3H, CH3 pyridine),
3.72 (s, 3H, OCH3),
3.81 (s, 3H, OCH3),
4.07 (q, J = 7.2 Hz,
2H, COOCH2CH3),
6.83-7.01 (m, 3H,
arom-H), 8.08 (s, 1H,
CH pyrimidine),
166.2 (CO ester), 163.9 (CO
lactam), 158.4, 157.1,
154.8, 148.9, 147.8,
142.9, 138.7, 135.8,
126.8, 124.4, 120.8,
113.9, 108.3, 106.6
(C-arom), 61.3
(CH2CH3), 55.9 (OCH3),
55.8 (OCH3), 24.3 (CH3
pyridine), 13.7 (CH2CH3)
12.82 (s, 1H, NH)
1.01 (t, J = 7.2 Hz, 3H,
COOCH2CH3), 2.61
(s, 3H, CH3 pyridine),
4.08 (q, J = 7.2 Hz,
2H, COOCH2CH3),
6.14 (s, 2H, OCH2O),
6.85-7.12 (m, 3H,
arom-H), 7.96 (s, 1H,
CH pyrimidine), 8.89
(s, br, 2H, NH2)
15a
3335, 3190 (NH2),
1725 (CO ester)
169.0 (CO ester), 161.2,
153.9, 152.2, 150.1,
148.7, 146.9, 143.6,
141.8, 140.9, 132.9,
126.7, 125.1, 118.8,
109.7, 107.9 (C arom),
101.2 (OCH2O), 61.7
(CH2CH3), 24.3 (CH3
pyridine), 13.9 (CH2CH3)
15b
3332, 3187 (NH2),
1717 (CO ester)
0.96 (t, J = 7.2 Hz, 3H,
COOCH2CH3), 2.66
(s, 3H, CH3
169.1 (CO ester), 161.1,
154.9, 152.1, 149.9,
148.5, 146.7, 143.6,
141.3, 140.8, 132.7,
126.5, 125.2, 118.7,
109.7, 107.9 (C-arom),
61.7 (CH2CH3), 55.9
(OCH3), 55.7 (OCH3),
24.3 (CH3 pyridine), 13.8
(CH2CH3)
pyrimidine), 3.70 (s,
3H, OCH3), 3.81 (s,
3H, OCH3), 4.06 (q,
J = 7.2 Hz, 2H,
COOCH2CH3),
6.83-7.01 (m, 3H,
arom-H), 8.08 (s, 1H,
CH pyrimidine), 8.90
(s, 2H, NH2)
16a
3163 (NH), 1722
(CO ester), 1658
(CO lactam)
0.98 (t, J = 7.2 Hz, 3H,
COOCH2CH3), 2.13
(s, 3H, CH3
166.3 (CO ester), 163.2 (CO
lactam), 162.3, 158.1,
156.7, 154.4, 149.7,
141.3, 137.8, 135.7,
127.1, 124.4, 119.5,
113.3, 112.3, 106.7
(C-arom), 101.2
pyrimidine), 2.61 (s,
3H, CH3 pyridine),
4.05 (q, J = 7.2 Hz,
2H, COOCH2CH3),
6.13 (s, 2H, OCH2O),
6.84–7.03 (m, 3H,
arom-H), 12.69 (s, 1H,
NH)
(OCH2O), 61.3
(CH2CH3), 24.3 (CH3
pyridine), 21.9 (CH3
pyrimidinone), 13.9
(CH2CH3)
(Continued on next page)

Cyanothioacetamide in Heterocyclic Synthesis
599
TABLE II IR and NMR Spectroscopic Data of Compounds 7, 9–16
(Continued)
IR [KBr, cm−1
]
1H NMR [δ, ppm]
13C NMR [δ, ppm]
16b 3160 (NH), 1720
(CO ester), 1655
(CO lactam)
0.97 (t, J = 7.2 Hz, 3H,
COOCH2CH3), 2.14 (s,
3H, CH3 pyrimidine),
2.62 (s, 3H, CH3
pyridine), 3.72 (s, 3H,
OCH3), 3.81 (s, 3H,
OCH3), 4.06 (q, J = 7.2
Hz, 2H, COOCH2CH3),
6.83–7.02 (m, 3H,
166.4 (CO ester), 164.0 (CO
lactam), 163.3, 158.2,
156.9, 154.6, 151.8, 142.8,
140.6, 138.2, 126.9, 124.4,
120.3, 113.8, 112.3, 108.4
(C-arom), 61.3 (CH2CH3),
55.8 (OCH3), 55.7 (OCH3),
24.3 (CH3 pyridine), 22.9
(CH3 pyrimidinone), 13.7
(CH2CH3)
arom-H), 12.71 (s, 1H,
NH)
EXPERIMENTAL
The melting points were determined on an electrothermal melting point
apparatus and are uncorrected. IR spectra were recorded on a Pye Uni-
cam SP 3-300 and a Shimadzu FT IR 8101 PC IR spectrophotometer
(KBr pellets). 1H and 13C NMR spectra were recorded on a Varian Mer-
cury VX-300 MHz NMR spectrometer in DMSO-d6 solution using TMS
as an internal reference. Electron impact mass spectra were obtained
with a 70 eV Shimadzu GCMS-QP 1000 EX spectrometer. Elemen-
tal analyses were carried out at the Microanalytical Center at Cairo
University, Giza, Egypt. The arylidine cyanothioacetamides 4a,b22,23
were prepared as previously reported.
Synthesis of Thioxo-1,6-dihydropyridine-3-carboxylates (7a,b)
Method A
A mixture of 4a,b (0.01 mol) and ethyl acetoacetate (1.3 g, 0.01
mol) in dioxane (30 mL) containing a catalytic amount of piperidine
(0.3 mL) was refluxed for 4 h. The solvent of the reaction mixture was
evaporated. The solid formed was collected by filtration, washed with
ethanol (15 mL), and crystallized from ethanol to give the respective
thioxopyridine 7.
Method B
A mixture of cyanothioacetamide (0.01 mol), ethyl acetoacetate (0.01
mol), and the respective aromatic aldehyde (0.01 mol) in dioxane
(30 mL) containing a catalytic amount of piperidine (0.3 mL) was heated

600
N. M. Abunada et al.
at reflux for 5 h. The solvent of the reaction mixture was evaporated,
and the crude product was collected, washed with ethanol (15 mL), and
crystallized from ethanol to give compounds 7a,b.
Synthesis of 3-Amino-6-methylthieno
[2,3-b]pyridine-5-carboxylates (9a,b–13a,b)
A solution of 7a,b (0.01 mol) in ethanol (50 mL) containing 10% potas-
sium hydroxide was treated with 8a–f (0.01 mol) and refluxed for
3 h. After cooling the reaction mixture was poured in ice-cold water
(50 mL). The solid formed was collected, washed with water (20 mL),
and crystallized from ethanol to give 9a,b–13a,b.
Synthesis of Ethyl
Pyrido[3,2:4,5]thieno[3,2-d]pyrimidine-8-carboxylates
(14a,b–16a,b)
A solution of 9a,b or 10a,b (0.01 mol) in an excess of formic acid (30
mL), a solution of 9a,b (0.01 mol) in an excess of formamide (30 mL),
or a solution of 10a,b (0.01 mol) in an excess of acetic anhydride (50
mL) was refluxed for 4 h. The reaction mixture was cooled to ambient
temperature, and the product formed was collected, washed with cold
ethanol (10 mL), and crystallized from ethanol to give the corresponding
products 14a,b–16a,b.
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