Synthesis of pyridothienopyridines and arylazothienopyridines

Article abstract of DOI:10.1080/714040977

Treatment of aminothienopyridine 3 with arylidenemalononitrile afford pyridothienopyridine 4. Also condensation of 3 with ethyl ethoxymethylene- cyanoacetae afford compound 5, which was cyclized in diphenyl ether into pyridothienopyridine 6. Thiourea deri

Full text of DOI:10.1080/714040977

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Phosphorus, Sulfur, and Silicon and the Related
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Synthesis of Pyridothienopyridines and
Arylazothienopyridines
Maisa I. Abdel Moneam a & Adel M. Kamal El-Dean a
a Assiut University, Assiut, Egypt
Published online: 18 Jun 2010.
To cite this article: Maisa I. Abdel Moneam & Adel M. Kamal El-Dean (2003) Synthesis of Pyridothienopyridines and
Arylazothienopyridines, Phosphorus, Sulfur, and Silicon and the Related Elements, 178:12, 2639-2651, DOI: 10.1080/714040977
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Phosphorus, Sulfur, and Silicon, 178:2639–2651, 2003
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Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500390248349
SYNTHESIS OF PYRIDOTHIENOPYRIDINES
AND ARYLAZOTHIENOPYRIDINES
Maisa I. Abdel Moneam and Adel M. Kamal El-Dean
Assiut University, Assiut, Egypt
(Received May 26, 2003; accepted July 2, 2003)
Treatment of aminothienopyridine 3 with arylidenemalononitrile af-
ford pyridothienopyridine 4. Also condensation of 3 with ethyl
ethoxymethylene-cyanoacetae afford compound 5, which was cyclized
in diphenyl ether into pyridothienopyridine 6. Thiourea derivative 7
was cyclized using Br2/AcOH, and ethyl chloroacetate to afford thi-
azolothienopyridine 8 and thiazolidinylthienopyridine 9 respectively.
Compound 15 was condensed with aromatic aldehydes to give the
corresponding arylidenethienopyridines 16a–d. The latter compounds
were underwent Michael addition with malononitrile to produce pyra-
nothienopyridines 17a–d. Compound 15 was coupled with aromatic
diazonium chloride to give the corresponding 2-arylazothienopyridine
derivatives 20, but when treated with nitrous acis it dimerised into
compound 19.
Thieno[2,3-b]pyridines are useful for multiple pharmacological appli-
cations. Thus, dihydrothieno[2,3-b]pyridine show remarkable effects
as calcium antagonists1 and also have been used in the treatment of
epilepsy, Alzheimer’s disease, and Huntington’s chorea.2 In continua-
tion of our program in the synthesis of heterocycles compounds contain-
ing thieno[2,3-b] pyridine moiety,3−10 we reported herein the synthesis
of some new thienopyridine derivatives with hope that have potential
biological activies.
Thus 3-amino-4,6-dimethylthieno[2,3-b]pyridine 3 allowed to react
with arylidene malononitrile afforded the 2-amino-4-aryl-7,9-dimethyl-
1,4-dihydropyrido[2ꢁ,3ꢁ:4,5]thieno[2,3-b]pyridine-3-carbonitrile (4a–c).
The aminothienopyridine 3 upon reaction with ethyl ethoxymethylene-
cyanoacetate gave compound 5. The latter compound was cyclized in
boiling diphenyl ether into 7,9-Dimethyl-4-oxo-1,4-dihydropyrido[2ꢁ,3ꢁ:
Address correspondence to Adel M. Kamal El-Dean, Chemistry Department, Faculty
of Science, Assiut University, Assiut 71516, Egypt. E-mail: a.eldean@acc.aun.edu.eg
2639

2640
M. I. Abdel Moneam and A. M. Kamal El-Dean
4,5]thieno[2,3-b]pyridine-3-carbonitrile (6). On the other hand, the com-
pound 3 was reacted with phenyl isothiocyanate gave the correspond-
ing thiourea derivative 7. The latter compound underwent readily cy-
clization when treated with bromine in acetic acid solution to give 8.
Treatment of thiourea derivative 7 with ethyl chloroacetate in the pres-
ence of sodium acetate solution afforded thiazoledinylthienopyridine 9
(Scheme 1).
SCHEME 1
On the other hand, the treatment of 4,6-dimethyl-2-mercapto-
pyridine-3-carbonitrile (10) with methyl 2-bromo-propionate gave com-
pound 11. When the latter compound boiled with methanolic solution
of sodium methoxide underwent cyclization accompanied with elimi-
nation of carboxylate group affording compound 12. Treatment amino

Thienopyridines
2641
compound 12 with phenyl isothiocyanate in benzene at reflux afforded
the corresponding thiourea derivative 13 which undergoes cylization
into thiazolidinone derivative 14 when treated with ethyl chloroacetate,
furnish the corresponding thienopyridin-3-one 1511 (Scheme 2).
SCHEME 2
Condensation of latter compound with aromatic aldehydes in reflux-
ing ethanol in the presence of catalytic amount of piperidine yield corre-
sponding 2-arylidenethienopyridine-3-one derivatives 16a–d. The lat-
ter compound was reacted with malononitrile in refluxing ethanol in the
presence of triethyl amine to afford pyranothienopyridine (17). Com-
pound 17a–c also was obtained by an alternative route via treatment of
15 with arylidenemalononitrile in refluxing ethanol and in the presence
of triethyl amine. Pyrano compound 17a was reacted with triethyl or-
thoformate in the presence of acetic anhydride to give the corresponding
ethoxymethylene amino derivative 18, which when treated with amines
or hydrazine hydrate underwent C N bond fission to produce compound
17. Attempt to synthesize 2-nitrozothieno-pyridin-3-one by its reaction
with nitrous acid lead to the formation of dimer 19 instead of nitrozo
compound. Also the dimmer compound 19 was produced when we try
to react α-β-unsaturated compound 16 with hydrazines to synthesize
pyrazolo compound, instead of the reaction of hydrazines with ketonic

2642
M. I. Abdel Moneam and A. M. Kamal El-Dean
group following with the addition into the double bond, it attacks the
double bond to form compound 15 again, followed by its dimerization.
The active methylene in compound 15 underwent coupling with aryl
diazinum chloride to give 2-arylazoderivatives 20 (Scheme 3).
SCHEME 3
EXPERIMENTAL
All melting points were uncorrected and were determined on a
Kofler melting point apparatus. The IR spectra were recorded on a

Thienopyridines
2643
1
Pye-Unicam spectrometer using KBr Wafer technique. HNMR spec-
tra were recorded on a Varian 390 90 MHz NMR spectrometer using
TMS as an internal standard. The chemical shift were expressed as
δ, units ppm. Mass spectra were recorded in on JEOL JMS 600 spec-
trometer. Elemental analyses were performed on a Perkin-Elmer 240
C microanalyzer. Compounds 1–3,15 were prepared by the following
published procedure.11
General Procedure for the Synthesis of 4a---c
A mixture of compound 3 (1.76 g, 0.01 mmol) and aryledinemalononi-
trile (0.01 mmol) in ethanol (30 ml), few drops of piperidine were added.
The mixture was heated under reflux for 3 h. The solid product so
formed on heating was collected and recrystallized from DMF as yellow
crystals.
2-Amino-1,4-dihydro-7,9-dimethyl-4-phenylpyrido[2ꢀ,3ꢀ:
4,5]thieno[2,3-b]pyridine-3-carbonitrile (4a)
Produced 78% yield, m.p. 298–300◦C. IR: ν = 3400 cm−1 (NH),
3200,3100 cm−1 (NH2) and 2220 cm−1 (CN). 1HNMR (DMSO-d6):
δ = 2.4, 2.7 (2s, 6H, 2CH3), 5.6 (s, 1H, CH-dihydropyridine), 6.5(s, 2H,
NH2), 6.9 (s, H, CH-pyridine), 7.3–7.8 (m, 5H, ArH) and 11.3 (s, 1H,
NH). MS; EI: m/z = 332 (M+).
Anal. Calcd. for C19H16N4S(332.42): C, 68.65; H, 4.85; N, 16.85;
S, 9.65%.; Found: C, 68.44; H, 4.83; 17.00; 9.37.
2-Amino-1,4-dihydro-7,9-dimethyl-4-(p-methoxyphenyl)-
pyrido[2ꢀ,3ꢀ:4,5]thieno-[2,3-b]pyridine-3-carbonitrile (4b)
Produced in 74% yield; m.p. 238–340◦C; IR: ν = 3420, 3320 cm−1
1
(NH2), 3170 cm−1 (NH) and at 2220 cm−1 (CN). HNMR (DMSO-d6):
δ = 2,4, 2.7(2s, 6H, 2CH3), 3.6(s, 3H, OCH3), 5.2(s, 1H, CH- dihydropy-
ridine), 6.3 (s, 2H, NH2), 6.9 (s, 1H, CH-pyridine), 7.4, 7.9 (2dd, 4H,
Ar H), 9.5 (s, 1H, NH).
Anal. Calcd. for C20H18N4OS(362.12): C, 66.28; H, 5.01; N, 15.46; S,
8.85%; Found: C, 66.04; H, 5.28; N, 15.66; S, 9.07.
2-Amino-4-(p-chlorophenyl)-1,4-dihydro-7,9-dimethyl-
pyrido[2ꢀ,3ꢀ:4,5]thieno-[2,3-b]pyridine-3-carbonitrile (4c)
Produced in 82% yield, m.p. 220–222◦C; IR: ν = 3500 cm−1 (NH),
3300, 3200 cm−1 (NH2) and 2210 cm−1 (CN). 1HNMR (DMSO-d6):
δ = 2.4, 2.7 (2s, 6H, 2CH3), 5.4(s, 1H, CH-dihydropyridine), 6.1 (s, 2H,
NH2), 6.9 (s, 1H, CH-pyridine), 7.1, 7.6 (2d, 4H, Ar H), 10.5 (s, 1H, NH).

2644
M. I. Abdel Moneam and A. M. Kamal El-Dean
Anal. Calcd. For C19H15ClN4S(366.87): C, 62.20; H, 4.12; N, 15.27;
S, 8.74; Cl, 9.66; Found: C, 62.42; H, 4.12; N, 15.17; S, 8.88; Cl, 9.85.
Ethyl 2-Cyano-3[4,6-dimethylthieno[2,3-b]pyridine-
3-yl]aminoacrylate (5)
A mixture of compound 3 (1.76 g, 0.01 mmol) and ethoxymethylene
ethyl cyanoacetate (1.70 g, 0.01 mmol) in ethanol (20 ml) and few drops
of acetic acid was added. The mixture was heated under reflux for 2 h,
then allowed to cool. The solid product was collected by filtration and
recrystallized from ethanol as yellowish white crystals in 78% yield, m.
p. 220–222◦C; IR: 3200 cm−1 (NH), 2210 (CN) and 1700 cm−1 (C O).
1HNMR (CDCl3): 1.4 (t, 3H, CH3), 2.6, 2.85 (2s, 6H, 2CH3), 4.35 (q, 2H,
CH2), 7.00 (s, 1H, CH-pyridine), 7.25(s, 1H, CH thiophene), 7.95(d, 1H,
CH N) and 11.25 (d, 1H, NH).
Anal. Calcd. for C15H15N3O2S(301.36): C, 59.78; H, 5.02; N, 13.94;
S, 10.64; Found: C, 60.02; H, 4.82; N, 14.08; S, 10.52.
7,9-Dimethyl-4-oxo-1,4-dihydropyrido[2’,3’:
4,5]thieno[2,3-b]pyridine-3-carbonitrile (6)
A solution of 5 (1.5 g, 0.005 mmol) in diphenyl ether (10 ml) was heated
under reflux for 3 h, then allowed to cool. The solid product which pre-
cipitated was collected by filtration and recrystallized from dioxan as
yellow crystals in 45% yield, m.p 310–312◦C; IR: ν = 3150 cm−1 (NH),
2220 cm−1 (CN), 1700 cm−1 (C O). 1HNMR(DMSO-d6): δ = 2.3, 2.7 (2s,
6H, 2CH3), 6.9, 7.3 (2s, 2H, CH-pyridine), and at 10.5 (s, 1H, NH). MS;
EI: m/z = 243(M+).
Anal. Cal. for C13H9N3OS(243.28): C, 61.16; H, 3.55; N, 16.46;
S, 12.56; Found: C, 61.04; H, 3.82; N, 16.67; S, 12.30.
N-(4,6-Dimethylthieno[2,3-b]pyridin-3-yl)-
N’-phenylthiourea (7)
A mixture of amino compound 3 (0.01 mmol) and phenyl isothiocyanate
(0.01 mmol) in benzene (30 ml) was heated under reflux for 2 h,
then allowed to cool. The solid product was collected and recrystal-
lized from ethanol as white crystals in 76% yield, m.p. 201–203◦C; IR:
ν = 3450, 3250 cm−1 (2NH), 2950 cm−1 (CH-aliphatic) and 1500 cm−1
1
(C S). HNMR (DMSO-d6): δ = 2.4,2.6 (2s, 6H, 2CH3), 6.7 (s, 1H, CH-
thiophene), 6.9 (s, 1H, CH-pyridine), 7.3–7.6 (m, 5H, Ar H), 9.8, and
11.4 (2s, 2H, 2NH).

Thienopyridines
2645
Anal. Calcd for C16H15N3S2(313.44): C, 61.31; H, 4.82; N, 13.41;
S, 20.46; Found: C, 61.12; H, 5.00; N, 13.53; S, 20.32.
2,4-Dimethyl-6-phenylaminothiazolo[4’,5’:4,5]thieno-
[2,3-b]pyridine (8)
To solution of thiourea derivative 7 (0.01 mmol) in acetic acid 30 ml,
bromine (0.01 mmol) in acetic acid (10 ml) was added dropwise with
stirring during 15 min. The stirring was continued for additional 1 h
and then (100 ml) water was added. The solid product was collected,
washed well with water and recrystallized from ethanol as yellowish
white crystals in 72% yield, m.p 199–200◦C. IR: ν = 3300 cm−1 (NH);
1HNMR (DMSO-d6): δ = 2.4, 2,6 (2s, 6H, 2CH3), 6.9 (s, 1H, CH-pyridine),
7–7.6 (m, 5H, Ar H), and 11.3 (s, 1H, NH). MS; EI: m/z = 311(M+).
Anal. Calcd for C16H13N3S2(311.42): C, 61.73; H, 4.21; N, 13.51;
S, 20.56; Found: C, 61.98; H, 4.06; N, 13.65; S, 20.76.
3-(4,6-Dimethyl-thieno[2,3-b]pyridine-3-yl)-
2-phenylimino-thiazolidin-4-one (9)
A mixture of compound 7 (3.13 g, 0.01 mmol), ethyl chloroacetate (1.22 g,
0.01 mmol), and sodium acetate (0.012 mmol) in ethanol (30 ml) was
heated under ereflux for 4 h, then allowed to cool, poured into cold water
(100 ml). The solid product was collected and recrystallized from ethanol
as white crystals in 69% yield, m.p. 188–190◦C; IR: ν = 1680 cm−1 (C O)
and 1600 cm−1 (C N). 1HNMR (CDCl3): δ = 2.3, 2,6 (2s, 6H, 2CH3), 4.1
(s, 2H, CH2), 6.9 (s, 1H, CH-pyridine), 7.3–7.8 (m, 5H, Ar H.
Anal. Calcd. for C18H15N3OS2(353.46): C, 61.17; H, 4.28; N, 11.89;
S, 18.14; Found: C, 60.99; H, 4.52; N, 12.08; S, 18.00.
Methyl 2-(3-Cyano-4,6-dimethylpyridin-2-yl)mercapto-2-
methylacetate (11)
A
mixture of compound 10 (1.64 g, 0.01 mmol), methyl 2-
bromopropionate (1.67 g, 0.01 mmol), and sodium acetate (0.012 mmol)
in methanol (30 ml) was refluxed for 2 h, then allowed to cool, and
poured into water. The solid product so formed was collected by filtra-
tion, recrystallized from a mixture of methanol/water (1:1) in 78% yield,
m.p. 64–66◦C; IR: ν = 2220 cm−1 (CN), and 1710 cm−1 (C O). 1HNMR
(CDCl3): δ = 1.5 (d, 3H, CH3), 2.3 (s, 6H, 2CH3), 3.3 (s 3H, CH3). 4.2–4.5
(q, 1H, CH) and 6.8 (s, 1H, CH-pyridine).
Anal. Calcd. For C12H14N2O2S (250.32): C , 57.58; H, 5.64; N, 11.19;
S, 12.81; Found: C , 57.72; H, 5.83; N, 10.98; S, 13.04.

2646
M. I. Abdel Moneam and A. M. Kamal El-Dean
3-Amino-2,4,6-trimethylthieno[2,3-b]pyridine (12)
Method A
A sample of compound 11 (2 g) was boiled for 1 h in methanol (30 ml)
containing sodium methoxide (0.02 mmol). The reaction mixture then
allowed to cool and poured into cold water (70 ml). The solid product
was filtered off and recrystallized from methanol as white crystals in
74% yield, m.p. 126–128◦C.
Method B
A mixture of compound 10 (1.64 g, 0.01 mmol), methyl-β-
bromopropionate (1.67 g, 0.01 mmol), and K2CO3 (0.02 mmol in
methanol (30 ml) was refluxed for 4 h then allowed to cool. The solid
product performed was collected by filtration, and recrystallized from
methanol as white crystals, in 70% yield, m.p. 126–128◦C; IR: ν = 3350,
3250 cm−1 (NH2). 1HNMR (CDCl3): δ = 2.2, 2.5, 2.7 (3s, 9H, 3CH3), 3.2–
3.5 (broad band, 2H, NH2) and 6.8 (s, 1H, CH pyridine).
Anal. Calcd. For C10H12N2S (192.28): C, 62.47; H, 6.29; N, 14.57;
S, 16.67; Found: C, 62.24; H, 6.08; N, 14.79; S, 16.84.
N-(2,4,6-Trimethylthieno[2,3-b]pyridin-3-yl)-
N’-phenylthiourea (13)
A mixture of compound 12 (1.93 g, 0.01 mmol) and phenyl isothio-
cyanate (1.35 g, 0.01 mmol) in benzene (30 ml) was refluxed for 5 h,
then allowed to cool. The solid product was collected and recrystal-
lized from ethanol as white crystals in 78% yield, m.p. 210–212◦C; IR:
ν = 3450 cm−1 and 3250 cm−1 (2NH). 1HNMR(CDCl3): 2.2, 2.5, 2.7 (3s,
9H, 3CH3), 6.9 (s, 1H, CH pyridine), 7,2–7.7 (m, 5H, ArH); 9.6, 11.3 (2s,
2H, 2NH).
Anal. Calcd. for C17H17N3S2 (327.46): C, 62.35; H, 5.23; N, 12.83;
S, 19.58 ; Found: C, 62.56; H, 5.00; N, 13.04; S, 19.72.
2-Phenylimino-3(2,4,6-Trimethyl-thieno[2,3-b]pyridin-
3-yl]-thiazolidin-4-one (14)
A mixture of compound 13 (3.27 g, 0.01 mmol), ethyl chloroacetate
(1.22 g, 0.01 mmol), and sodium acetate (0.012 mmol) in ethanol (30 ml)
was heated under reflux for 5 h, then allowed to cool and poured into
cold water (100 ml). The solid product was collected and recrystallized
from ethanol as white crystals, in 67% yield, m.p. 227–230◦C; 1HNMR
(CDCl3): δ = 2.3, 2.5, 2,8 (3s, 9H, 3CH3), 4.1 (s, 2H, CH2), 6.9 (s, 1H, CH
pyridine), 7.3–7.9 (m, 5H, ArH) and 8.3 (broad s, 1H, NH).

Thienopyridines
2647
Anal. Calcd. For C19H17N3OS2 (367.49): C, 62.10; H, 4.66; N, 11.43;
S, 17.45; Found: C, 62.12; H, 4.39; N, 11.18; S, 17.56.
General Procedure for the Synthesis of 16a--d
To a mixture of compound 15 (0.01 mmol) and aryl aldehyde (0.01 mmol)
in ethanol (30 ml), and a few drops of piperidine were added. The mix-
ture was heated under reflux for 2 h, then allowed to cool. The solid
product was collected and recrystallized from dioxan.
2-Benzyledine-4,6-dimthyl-1,2-dihydrothieno[2,3-
b]pyridin-3-one (16a)
Produced in 77% yield, m.p. 174–176◦C; IR: ν = 3050 cm−1 (CH-
1
aromatic) and 1690 cm−1 cm−1. HNMR (DMSO-d6): δ = 2.3, 2.5 (2s,
6H, 2CH3), 6.7 (s, 1H, C CH), 6.9 (s, 1H, CH-pyridine) and 7.3–7.6 (m,
5H, ArH).
Anal. Calcd. for C16H13NOS(267.35): C, 71.85; H, 4.90; N, 5.24;
S, 11.99; Found: C, 71.63; H, 5.13; N, 5.53; S, 12.23.
4,6-Dimthyl-1,2-dihydro-2-(4-methoxybenzyledine)thieno-
[2,3-b]pyridin-3-one (16b)
Produced in 85% yield, m.p. 182–184◦C; IR: ν = 1690 cm−1 (CO).
1HNMR (DMSO-d6): δ = 2.3, 2.5 (2s, 6H, 2CH3), 3.2 (s, 3H, OCH3),
6.9 (s, 1H, CH-pyridine) and 7.1,7.6 (2d, 4H, ArH), 7.8 (s, 1H,
C CH).
Anal. Calcd. for C17H15NO2S(297.37): C, 68.66; H, 5.08; N, 4.71;
S, 10.78%. Found: C, 68.39; H, 4.87; N, 4.95; S, 11.00.
2-(4-Chlorobenzyledine)-4,6-dimthyl-1,2-dihydrothieno-
[2,3-b]pyridin-3-one (16c)
Produced in 78% yield, m.p. 199–200◦C; Lit.[13] m.p. 198◦C.
4,6-Dimthyl-1,2-dihydro-2-(4-hydroxybenzyledine) thieno-
[2,3-b]pyridin-3-one (16d)
Produced in 72% yield, m.p. > 300◦C; IR: ν = 3450 cm−1 (OH) and
1
1690 cm−1 (CO). HNMR (DMSO-d6): δ = 2.3, 2.5 (2s. 6H, 2CH3), 6.9
(s, 1H, CH-pyridine) and 7.2, 7.8 (2d, 4H, ArH), 8.0 (s, 1H, C CH) and
9.3 (s, 1H, OH).
Anal. Calcd. for C16H13NO2S (283.35): C, 67.82; H, 4.62; N, 4.94;
S, 11.32. Found: C, 67. 98; H, 4.83; N, 5.17; S, 11.53.

2648
M. I. Abdel Moneam and A. M. Kamal El-Dean
General Procedure for the Synthesis of 17a--c
Method A
A mixture of 16 (0.01 mmol), malononitrile (0.01 mmol), and few
drops of piperidine in ethanol (30 ml), was heated under reflux for 2 h,
then allowed to cool. The solid product was collected and recrysalized
from ethanol.
Method B
A mixture of compound 15 (0.01 mmol), arylidenemalononitrile (0.01
mmol), and few drops of triethyl amine as a catalyst in ethanol (30 ml)
was refluxed for 3 h, then allowed to cool. The solid product was collected
and recrystallized from ethanol.
2-Amino-7,9-dimethyl-4[H]-4-phenyl-pyrano[2ꢀ,3ꢀ:4,5]-
thieno[2,3-b]pyridine-3-carbonitrile (17a)
Produced 78% yield, m.p. 265–268◦C; IR: ν = 3340, 3230 cm−1 (NH2),
2210 cm−1 (CN). 1HNMR (CDCl3): 3.4, 3.6 (2s, 6H, 2CH3), 4.7(s, 1H, CH-
pyran), 6.5 (s, 2H, NH2), 6.9 (s,1H,CH-pyridine), 7.0–7.4 (m, 5H, Ar H).
Anal. Calcd. for C19H15N3OS (333.41): C, 68.45; H, 4.53; N, 12.60; S,
9.62. Found: C, 68.68; H, 4.77; N, 12.42; S, 9.78.
2-Amino-7,9-dimethyl-4[H]-4-[4-methoxyphenyl]pyrano-
[2ꢀ,3ꢀ:4,5]thieno[2,3-b]pyridine-3-carbonitrile (17b)
Produced in 87% yield, m.p. 183–185◦C; IR: ν = 3360, 3260 cm−1
(NH2), and at 2220 cm−1 (CN). 1HNMR (DMSO-d6): δ = 2.3, 2.7(2s, 9H,
3CH3), 3.6(s, 3H, OCH3), 4.6 (s, 1H, CH-pyran), 6.9 (s, 1H, CH-pyridine)
and at 7.0, 7.6 (2d, 4H, Ar H).
Anal. Calcd. for C20H17N3O2S (363.10): C, 66.10; H, 4.71; N, 11.56;
S, 8.82. Found: C, 66.00; H, 5.00; N, 11.72; S, 9.00.
2-Amino-[4-chlorophenyl]-7,9-dimethyl-4[H]-
pyrano[2ꢀ,3ꢀ:4,5]thieno[2,3-b]pyridine-3-carbonitrile (17c)
Produced in 82% yield, m.p. 288–290◦C; IR: ν = 3380, 3280 cm−1
1
(NH2), and at 2220 cm−1 (CN). HNMR (DMSO-d6): δ = 2.4, 2.7 (2s,
6H, 2CH3), 4.7 (s, 1H, CH-pyran), 6.9 (s, 1H, CH-pyridine) and at 7.1,
7.6 (2d, 4H, Ar H).
Anal. Calcd. for C19H14ClN3OS (367.85): C, 62.04; H, 3.84;Cl, 9.64;
N, 11.42; S, 8.72. Found: C, 61.88; H, 4.07;Cl. 9.78; N, 11.32; S, 8.78.

Thienopyridines
2649
2-Ethoxymethyleneamino-4-phenyl-4[H]7,9-
dimethylpyrano[2’,3’:4,5]thieno[2,3-b]pyridine-
3-carbonitrile (18)
A mixture of compound 17a (3.33 g, 0.01 mmol) and triethyl orthofor-
mate (0.02 mmol) in acetic anhydride (20 ml) was heated under reflux
for 2 h, allowed to cool, and poured into (100 ml). The solid product was
collected and recrystallized from ethanol as white crystals in 72% yield,
1
m.p. 210–213◦C; IR: 2220 cm−1 (CN). HNMR (CDCl3): δ = 1.4–1.6 (t,
3H, CH3), 2.5. 2.7 (2s, 6H, CH3). 4.3–4.6 (q. 2H, CH2), 4.95 (s, 1H, CH-
pyran). 6.9 (s, 1H, CH-pyridine), 7.1–7,5 (m, 5H, Ar H). and 8.2 (s, 1H,
CH N).
Anal. Calcd. For C22H19N3O2S (389.47): C, 67.85; H, 4.92; N, 10.79;
S, 8.23. Found: C, 68.05; H, 4.16; N, 10.52; S, 8.05.
4,6,4’,6’-Tetramethyl[2.2’]bi[thieno]2,3-b]pyridinylidene-
3,3’-dione(19)
Method A
A mixture of compound 16a (2.67 g, 0.01 mmol) and phenyl hy-
drazine (1.08 g, 1.0 mmol) in ethanol (30 ml) was heated under reflux for
3 h. The red crystals, which precipitated while heating, was filtered off
while hot and identified as compound 19. The filtrate was evaporated
and the residue was identified as benzyledine phenyl hydrazone. m.p.
lit.12
Method B
To a stirred solution of compound 15 (1.79 g, 0.01 mmol) in acetic acid
(20 ml), sodium nitrite solution (0.02 mmol) in water (5 ml) was added
dropwise over 10 min. The solid product was collected and recrystallized
from dioxan in 78% yield and identified as compound 19. Produced
as red crystals in 65% yield, m.p. > 300◦C; IR: ν = 1680 cm−1 (C O).
1HNMR( CF3COOD): 2.4. 2.6 (2s, 12H, 4CH3) and at 7.0 (s, 2H, 2CH-
pyridine). MS; EI: m/z = 354(M+).
Anal. Calcd for C18H14N2O2S2 (354.44): C, 61.00; H, 3.98; N, 7.90;
S, 18.09. Found: C, 60.78; H, 4.24; N, 8.13; S, 17.
2-Arylazo-4,6-dimthylthieno[2,3-b]pyridin-3-one (20)
To a solution of compound 15 (1.79 g, 0.01 mmol) in ethanol contain-
ing 0.05 mmol sodium acetate, a solution of diazotized aromatic amine
(0.01 mmol) was added dropwise with stirring at 5◦C over 16 min.
After the addition was complete the stirring was continued for 1 h,

2650
M. I. Abdel Moneam and A. M. Kamal El-Dean
then allowed to stand for 2 h. The solid product was collected and re-
crystallized from ethanol.
4,6-Dimthyl-2-phenylazothieno[2,3-b]pyridin-3-one (20a)
Produced in 78% yield, m.p. 178◦C; IR: 3350 cm−1 (NH). 1680 cm−1
(C O). 1HNMR(CDCl3); δ = 2.4, 2.6 (2s, 6H, 2CH3), 6.9 (s, 1H, CH-
pyridine), 7.1–7.6 (m, 5H, Ar H), 11.2 (s, 1H, NH).
Anal. Calcd. for C15H13N3OS (283.35): C, 63.58; H, 4.62; N, 14.83; S,
11.31. Found: C, 63.75; H, 4.77; N, 15.05; S, 11.08.
4,6-Dimthyl-2-(4-methylphenyl)-azothieno[2,3-b]pyridin-
3-one (20b)
Produced in 76% yield, m.p. 180◦C; IR: 3350 cm−1 (NH). 1680 cm−1
(C O). 1HNMR (CDCl3); δ = 2.2, 2.4, 2.6 (3s, 9H, 3CH3), 6.9 (s, 1H, CH-
pyridine), 7.0–7.6 (2d, 4H, Ar H), 9.9, 13.2 (2s, 1H, NH OH tautomer).
Anal. Calcd. for C16H15N3OS (297.37): C, 64.62; H, 5.08; N, 14.13;
S, 10.78. Found: C, 64.88; H, 4.88; N, 13.84; S, 11.00.
4,6-Dimthyl-2-(4-methoxyphenyl)-azothieno[2,3-b]pyridin-
3-one (20c)
Produced in 82% yield, m.p. 205◦C; IR: 3350 cm−1 (NH). 1680 cm−1
(C O).
Anal. Calcd. for C16H15N3O2S (313.37): C, 61.32; H, 4.82; N, 13.41;
S, 10.23. Found: C, 61.15; H, 5.05; N, 13.67; S, 10.04.
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2651
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