Novel syntheses and reactions of polynuclear heterocyclic derivatives derived from thioxopyridopyrimidine, with a new ring system

Article abstract of DOI:10.1080/10426500500543768

Pyridopyrimidine derivatives 2 reacted with hydrazonoylchloride derivatives and yielded triazolopyridopyrimidines 6a-f. Compound 4b reacted with aliphatic acids and afforded triazolo-pyridopyrimidines 7a,b, and the reaction with carbon disulfide afforded

Full text of DOI:10.1080/10426500500543768

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Novel Syntheses and Reactions
of Polynuclear Heterocyclic
Derivatives Derived From
Thioxopyridopyrimidine, With
a New Ring System
A. B. A. Elgazzar a , A. M. Gafaar a , H. N. Hafez a &
A. S. Aly a
a Department of Photochemistry (Heterocycle and
Nucleoside Unit), National Research Center, Dokki,
Giza, Egypt
Available online: 01 Feb 2007
To cite this article: A. B. A. Elgazzar, A. M. Gafaar, H. N. Hafez & A. S. Aly (2006):
Novel Syntheses and Reactions of Polynuclear Heterocyclic Derivatives Derived From
Thioxopyridopyrimidine, With a New Ring System, Phosphorus, Sulfur, and Silicon and
the Related Elements, 181:8, 1859-1883
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Phosphorus, Sulfur, and Silicon, 181:1859–1883, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500500543768
Novel Syntheses and Reactions of Polynuclear
Heterocyclic Derivatives Derived From
Thioxopyridopyrimidine, With a New Ring System
A. B. A. Elgazzar
A. M. Gafaar
H. N. Hafez
A. S. Aly
Department of Photochemistry (Heterocycle and Nucleoside Unit),
National Research Center, Dokki, Giza, Egypt
Pyridopyrimidine derivatives 2 reacted with hydrazonoylchloride derivatives and
yielded triazolopyridopyrimidines 6a–f. Compound 4b reacted with aliphatic acids
and afforded triazolo-pyridopyrimidines 7a,b, and the reaction with carbon disul-
fide afforded 10-mercapto-triazolopyridopyrimidine (10). Moreover, the reaction
of 4b with β-ketoesters afforded 10-pyrazolyl-pyridopyrimidines derivatives 11,
13, 14, and 15. Compound 4b reacted with nitrous acid to give tetrazolopyri-
dopyrimidine 16, which reduced to 10-amino-derivative 17. On the other hand,
the reaction of 4b with aromatic aldehydes afforded arylidines derivatives 18a–
c, which were later cyclized to triazolo-pyridopyrimidines deivatives 19a–c. Fi-
nally, 4b reacted with α-haloketones to give triazines derivativrs 20, with new ring
systems.
Keywords New ring system; polynuclear heterocyclic; pyrimido[4,5-b]quinolone deriva-
tives; thioxopyrido pyrimidine
INTRODUCTION
It is known that pyridopyrimidine derivatives have biochemical activi-
ties against bacteria.1,2 Moreover, they are used for the treatment of
intestinal, urinary, and biliary tract infection in humans.3,4 These
derivatives also have similar inherent chemotherapeutic properties.5
Moreover, biological activities of condensed pyrimidine derivatives act
as sedatives6,7 and analgesic,8 antiinflammatory,9 anticonvulasnt,10
and antimicrobial agents.11
Received July 14, 2005; accepted October 20, 2005.
Address correspondence to A. B. A. Elgazzar, National Research Center, Department
of Photochemistry (Heterocycle and Nucleoside Unit), El-Tahrir St., Dokki, Giza, Egypt.
E-mail: elgazzar2000@hotmail.com
1859

1860
A. B. A. Elgazzar et al.
The rapid growth in the literature dealing with the synthesis biolog-
ical activity of the pyridopyrimidine derivatives prompted us to start a
program to synthesize some new pyridopyrimidine derivatives.
This report describes our approach to the synthesis of polyfunc-
tional heterocyclic compounds.12,13 In addition, we reported conve-
nient methods for the synthesis of triazolopyrido-pyrimidines 7, 9,
10, and 19; tetrazolopyridopyrimidines 16; and triazinopyridopyrim-
idines 20. Thus, heating under reflux 6-aminothiouracil with chalcones
1a–e in boiling dimethylformamide for long times afforded a mixture
of the oxidizing form of 7-(4-aryl)-10-thioxo-5,6,10,11-tetrahydro-9H-
benzo[h]pyrimido[4,5-b]quinolin-8-ones 2a–e (60–70%), and nonoxi-
dizes formed 2ꢀ (30–40%). The oxidized form, which separated by
crystalization, reacted with methyl iodide to give the corresponding
1
10-methylthio derivative 3 (Scheme 1). H NMR spectra of the result-
1
ing products were agreement with the structures. The H-NMR spec-
trum (DMSO-d6) of 2d as an example showed signals at δ 2.42–2.47
(m, 2H, CH2), 2.75–2.80 (m, 2H, CH2), 4.15 (s, 3H, OCH3) 7.18–7.22
(d, 2H, p-pheny), 7.30–7.37 (m, 1H, phenyl), 7.44–7.47 (m, 2H, phenyl),
7.58–7.61 (d, 2H, phenyl), 8.32–8.38 (m, 1H, phenyl), and 12.10, 12.60
(two NH, D2O exchangable). The oxidized pyridopyrimidine derivative
2b reacted with hydrazonoyl chlorides 5a–f to give novel functional-
ized heterocycles having pyridine rings condensed with other important
heterocycles, such as 7-(4-aryl)-5,6-dihydro-9H-benzo[h]-1,2,4-triazolo-
[4ꢀ,3ꢀ:1,2]pyrimido[4,5-b]quinolin-8-one derivatives 6a–f (Scheme 2).
1
The correct values in elemental analysis and IR, H NMR, and mass
spectra of compounds 6a–f are in agreement with the assigned struc-
tures. The N-3 nitrogen atom and not the N-1 nitrogen atom was in-
volved in the cyclization to form the adduct 6, not 6. The 1H NMR
spectrum of 6e as an example showed signals at δ 1.25 (t, 3H, CH3),
2.35–2.45 (m, 2H, CH2), 2.65–2.80 (m, 2H, CH2) 4.40 (q, 2H, CH2),
7.25–7.30 (d, 2H, phenyl), 7.31–7.35 (m, 1H, phenyl), 7.40–7.75 (m, 7H,
5H (phenyl) +2H (phenyl), 8.05–8.10 (d, 2H, phenyl), and 8.30–8.35 (d,
1H, phenyl). The mass spectrum showed the molecular ion peak at m/z,
547 (100%).
Mercapto groups may be removed in favor of hydrogen by desul-
furization using alkaline hydrazine hydrate.14,15 Therefore, the 7-
(4-chlorophenyl)-10-hydrazino-5,6,10,11-tetrahydro-9 H-benzo[h]pyri-
mido[4,5-b]quinolin-8-one (4b) is a fertile source to enrich the
synthesis of heterocyclic chemistry with several new azolopyridopyrim-
idines, pyridopyrimido-as-triazines, and pyrazolylpyridopyrimidines
(Scheme 3). Thus, heating under reflux 4b with aliphatic acids, mainly,
formic and acetic acids, for 6 h yielded 7-(4-chlorophenyl)-5,6-di-
hydro-9 H-benzo[h]-1,2,4-triazolo[4ꢀ,3ꢀ:1,2]pyrimido[4,5-b]quinolin-8-
one derivatives 7a,b. Besides the correct values in elemental analyses,

Polynuclear Heterocyclic Derivatives
1861
SCHEME 1
the 1H NMR spectrum of 7a, as an example, showed signals at δ 2.52–
2.60 (m, 2H, CH2), 2.75–2.85 (m, 2H, CH2), 7.20–7.25 (d, 2H, phenyl),
7.27–7.33 (m, 1H, phenyl), 7.40–7.45 (m, 2H, phenyl), 7.50–7.55 (d, 2H,
phenyl) 8.50–8.55 (m, 1H, phenyl), 9.50 (s, 1H, H triazole), and 12.65
(brs, 1H, NH, D2O exchangable), and they are in agreement with the
assigned structure. On the other hand, heating under reflux compound
4b with acetic acid for 3 h yielded the 2-acethydrazido derivative 8.
The IR spectrum of 8 displayed absorption bands at 3389, 3100 cm−1
(brs, 2NH), 1709 cm−1 (CO), and 1686 cm−1 (CO).
The derivative 4b reacted with potassium thiocyanate in boiling
acetic acid to give compound 9. Besides the correct values in elemental
analysis, the spectral data of 9 are in agreement with the assigned
structure. Similarly, heating 4b with carbon disulphide in ethanolic
potassium hydroxide gave 7-(4-chlorophenyl)-5,6-dihydro-9H-10-
thioxobenzo[h]-1,2,4-triazolo[4ꢀ,3ꢀ :1,2]pyrimido[4,5-b]quinolin-8-one

1862
A. B. A. Elgazzar et al.
SCHEME 2
(10). The IR spectrum of 10 displayed absorption bands at 3465 cm−1
(NH) and 1168 cm−1 (CO).
1
The H NMR spectrum (DMSO-d6) of 10 showed signals at δ 2.40–
2.55 (m, 2H, CH2), 2.80–3.00 (m, 2H, CH2), 7.15–7.25 (d, 2H, phenyl),
7.30–7.40 (m, 1H, phenyl), 7.45–7.50 (m, 2H, phenyl), 7.51–7.55 (d,

Polynuclear Heterocyclic Derivatives
1863
2H, phenyl), 8.75–8.80 (m, 1H, phenyl), 12.55 (brs, 1H, NH, D2O ex-
changable), and 13.65 (brs, 1H, NH, D2O exchangable). Mass spectra
of 10 showed the molecular ion peak at m/z 431.
Moreover, the 10-hydrazino derivative 4b reacted with some β-
cyanoesters, β-ketooesters, and β-diketones to form derivatives 11, 12,
and 15. Compound 4b and ethyl cyanoacetate in hot ethanolic sodium
ethoxide solution afforded the 10-(3-amino-5-hydroxy-4H-pyrazol-l-yl)
derivative 11. The IR spectrum of 11 displayed absorption bands
at 3318 cm−1 (NH) and 1687 cm−1 (CO). Its 1H NMR spectrum
(DMSO-d6) showed signals at δ 2.36–2.43 (m, 2H, CH2), 2.67–2.75
(m, 2H, CH2), 3.57 (s, 2H, CH2), (7.17–7.25 (d, 2H, phenyl), 7.27–
7.34 (m, 1H, phenyl), 7.43–7.50 (m, 2H, phenyl), 7.53–7.58 (d, 2H,
phenyl), 8.41–8.43 (m, 1H, phenyl), and 12.20, 12.85 (two brs, NH,
D2O exchangable). Similarly, 4b reacted with ethyl acetoacetate in
absolute ethanol and gave the ethylacetoacetate hydrazone derivative
12, while the 7-(4-chlorophenyl)-10-(3-methyl-4H-pyrazol-5-one-1-yl)-
5,6,10,11-tetrahydro-9H-benzo-[h]pyrimido[4,5-b]quinolin-8-one (13)
was produced by heating 4b with ethyl acetoacetate under reflux in
ethanolic sodium ethoxide. Compound 12 could be converted to 13
upon additional heating with ethanolic sodium ethoxide solution.
The 1H NMR spectrum (DMSO-d6) of 12 showed signals at δ 1.25
(t, 3H, CH3), 2.00 (s, 3H, CH3), 2.35–2.45 (m, 2H, CH2), 2.70–2.85
(m, 2H, CH2), 3.35 (s, 2H, CH2), 4.15 (q, 2H, CH2), 7.15–7.25 (d,
2H, phenyl), 7.25–7.30 (m, 1H, phenyl), 7.30–7.35 (m, 2H, phenyl),
7.40–7.50 (d, 2H, phenyl), 8.20–8.30 (m, 1H, phenyl), 9.80–10.40 (brs,
1H, NH, D2O exchangable), and 11.15 (brs, NH, D2O exchangable).
The IR spectrum displayed absorption bands 3250 cm−1 (brs, NH),
1740, 1680 cm−1 (2CO), and 1580 cm−1 (C N). The 1H NMR spec-
trum of 13 showed no signals corresponding to ethyl group protons.
Compound 13 was coupled with phenyl diazonium salts to afford
7-(4-chlorophenyl)-10-(3-methyl-4-phenylazopyrazol-5-one-1-yl)-5,6,10,
11-tetra-hydro-9H-benzo[h]pyrimido[4,5-b]quinolin-8-one(14). The IR
spectra of 14 showed absorption bands at 3436 cm−1 (OH), 3250 cm−1
1
(NH), 2917 cm−1 (CH aliphatic), and 1686 cm−1 (CO). The H NMR
spectrum showed signals at δ 2.41 (s, 3H, CH3), 2.49–2.54 (m, 2H,
CH2), 2.80–2.85 (m, 2H, CH2), 7.19–7.21 (m, 1H, phenyl), 7.25–7.28 (d,
2H, phenyl), 7.30–7.36 (m, 1H, phenyl), 7.38–7.47 (m, 6H, 2H, phenyl
+4H, phenyl), 7.49–7.56 (d, 2H, phenyl), 8.40–8.41 (m, 1H, phenyl),
and 11.20 (brs, NH, D2O exchangable). The mass spectrum for 14
showed the molecular ion peak at m/z 560 (100%).
When equimolar amounts of 4b and pentane-2,4-dione deriva-
tives were heated under reflux in ethanol, the 7-(4-chlorophenyl)-
10-(3-methyl-4-(un)substituted-5-substituted pyrazol-1-yl)-5,6,10,

1864
A. B. A. Elgazzar et al.
SCHEME 3
11-tetrahydro-9H-benzo[h]pyrimido[4,5-b]quinolin-8-ones (15a–c)
were obtained in good yield. Besides the correct values in elemental
analysis, the spectral data of 15a–c are in agreement with the as-
1
signed structure. The H NMR spectrum (DMSO-d6) of 15a, as an ex-
ample, showed signals at δ 2.25 (s, 3H, CH3), 2.45–2.55 (m, 2H, CH2),
2.65 (s, 3H, CH3), 2.70–2.85 (m, 2H, CH2), 6.40 (s, 1H,pyrazol pro-
ton), 7.20–7.25 (d, 2H, phenyl), 7.27–7.35 (m, 1H, phenyl), 7.45–7.50
(m, 2H, phenyl), 7.52–7.57 (d, 2H, phenyl), 8.35–8.40 (m, 1H, phenyl),
and 11.90, (brs, NH, D2O exchangable). Its IR spectrum displayed ab-
sorption bands at 3320 cm−1 (brs, NH), 3054 cm−1 (CH aryl), 2943 cm−1

Polynuclear Heterocyclic Derivatives
1865
(CH alkyl), 1693 cm−1 (CO), 1600 cm−1 (C N), and 1550 cm−1 (C C).
Its mass spectrum showed the molecular ion peak at m/z 453.
The treatment of compound 4b with nitrous acid at 0◦C led
to the formation of 7-(4-chlorophenyl)-5,6,12-trihydro-9H-benzo[h]-
tetrazolo[4ꢀ,5ꢀ:1,2]pyrimido[4,5-b]quinolin-8-one (16). IR spectra for
compound 16 showed absorption bands at 3243 cm−1 (brs, NH), 2934
cm−1 (CH alkyl), 1700 cm−1 (CO), 1629 cm−1 (N N), and 1582 cm−1
(C N). The 1H NMR spectrum of 16 (DMSO-d6) showed signals at
δ 2.45–2.50 (m, 2H, CH2), 2.80–2.90 (m, 2H, CH2), 7.20–7.25 (d, 2H,
phenyl), 7.27–7.31 (m, 1H, phenyl), 7.40–7.60 (m, 4H, 2H phenyl
+ 2H phenyl), 8.25–8.35 (m, 1H, phenyl), and 13.25, (brs, NH, D2O
exchangable). Compound 16 was reduced to 10-amino-7-(4-Chloro-
phenyl)-5,6,10,11-tetrahydro-9H-benzo[h]pyrimido-[4,5-b]quinolin-8-
one (17) by zinc dust in acetic acid. The 1H NMR spectrum (DMSO-d6)
of 17 showed signals at δ 2.30–2.40 (m, 2H, CH2), 2.80–2.90 (m,
2H, CH2), 3.55–3.60 (brs, 2H, NH2 D2O exchangable), 4.45 (brs,
NH, D2O exchangable), 7.15–7.30 (m, 1H, phenyl), 7.35–7.40 (d, 2H,
phenyl), 7.45–7.50 (m, 3H, 2H phenyl + 1H phenyl), and 7.70–7.75
(m, 1H, phenyl). Its IR spectrum displayed absorption band at 3310
cm−1 (NH2). The mass spectrum for the same compound showed the
molecular ion peak at m/z 374 (100%).
According to Shishoo and Jain,15 10-hydrazinobenzo[h]pyrimido[4,5-
b]quinolin-8-one (4b) gave 7-(4-chlorophenyl)-10-(aryl-methylenehy-
drazone)-5,6,10,11-tetrahydro-9H-benzo[h]pyri-mido[4,5-b]quinolin-8-
one derivatives 18a–c when 4b was treated with the appropriate
aldehyde in boiling dioxane in the presence of catalytic amounts of
piperidine. Compounds 18a–c gave compatible spectral and analytical
data. The 1H NMR (DMSO-d6) spectrum of compound 18c, as an
example, showed signals at δ 2.45–2.50 (m, 2H, CH2), 2.75–2.85 (m,
2H, CH2), 3.85 (s, 3H, OCH3), 6.95–7.05 (d, 2H, phenyl), 7.20–7.25 (d,
2H, phenyl), 7.26–7.30 (m, 1H, phenyl), 7.40–7.45 (m, 2H, phenyl),
7.47–7.50 (d, 2H, phenyl),7.85–7.95 (d, 2H, phenyl) 8.05–8.11 (s, 1H,
methylenic proton), 8.30–8.40 (m, 1H, phenyl), and 11.20 (brs, NH,
D2O exchangable). The arylhydrazones 18a–c could be cyclized into the
corresponding 10-aryl-7-(4-chlorophenyl)-5,6-dihydro-9H-benzo[h]-1,2,
4-triazolo[4ꢀ,3ꢀ:1,2]pyrimido[4,5-b]quinolin-8-one 19a–c, when treated
with excess bromine in acetic acid in presence of anhydrous sodium
acetate. IR spectra of compounds 19 displayed absorption bands around
1
3290 cm−1 (NH) and 1690 cm−1 (CO). The H NMR (DMSO-d6) spec-
trum of compound 19b, as an example, showed signals at δ 2.43–2.50
(m, 2H, CH2), 2.75–2.83 (m, 2H, CH2), 7.15–7.20 (d, 2H, phenyl),
7.25–7.30 (m, 1H, phenyl), 7.35–7.45 (m, 2H, phenyl), 7.45–7.55 (two

1866
A. B. A. Elgazzar et al.
SCHEME 4
d, 4H, phenyl), 7.98–8.15 (d, 2H, phenyl), 8.29–8.38 (m, 1H, phenyl),
and 11.65 (brs, NH, D2O exchangable).
Finally, the 10-hydrazino derivative 4b was used for the preparation
of 7-(4-chlorophenyl)-5,6-dihydro-9H-11-(methyl or phenyl)benzo
[h]-1,2,4-triazino[4ꢀ,3ꢀ:1,2]pyri-mido[4,5-b]quinolin-8-one derivatives
20a,b. Thus, heating 4b under reflux with chloro-acetone or phenacyl
bromide in dry xylene yielded directly the triazino derivatives 20a,b
(Scheme 4). IR spectra of 19 displayed absorption bands around 3420
cm−1 (NH) and 1687 cm−1 (CO). The 1H NMR (DMSO-d6) spectrum of
compound 20a, as an example, showed signals at δ 2.05 (s, 3H, CH3),
2.50–2.55 (m, 2H, CH2), 2.70–2.85 (m, 2H, CH2), 4.80 (s, 2H, CH2),
7.20–7.30 (d, 2H, phenyl), 7.35–7.40 (m, 1H, phenyl), 7.45–7.55 (m, 4H,
2H phenyl + 2H phenyl), 8.25–8.40 (m, 1H, phenyl), and 11.05 (brs,
NH, D2O exchangable). Its mass spectrum showed the molecular ion
peak at m/z 427 (100%).
EXPERIMENTAL
1
All melting points were uncorrected. H NMR and 13C NMR spectra
were recorded on Bruker (WM-250 MHz), Bruker (AC-250 MHz)

Polynuclear Heterocyclic Derivatives
1867
spectrometers, and a Varian 300 MHz Oxford-Mercury spectrometer
(National Research Center, Giza, Egypt). Chemical shifts were ex-
pressed as δ values aganist SiMe4 as internal standards. IR spectra
were recorded as potassium bromide pellets on a Perkin-Elmer 1430
spectrometer, (National Research Center and the Department of
chemistry Cairo University, Giza, Egypt). Mass spectra were recorded
on GCMS-QP 1000 EX Shimadzu Japan (gas chromatography-mass
spectrometer). Microanalytical data were obtained by the Microanalyt-
ical Center at Cairo University and National Research Center (Egypt).
The starting materials are prepared according to Quiroga et al.15 and
El-Gazzar.16
7-Aryl-10-thioxo-5,6,10,11-tetrahydro-9H-benzo[h]pyrimido-
[4,5-b]quinolin-8-one (2a–e)
General Procedure
A mixture of compound 1 (10 mmol) and 6-aminothiouracil (1.43 g,
10 mmol) was refluxed in 50 mL of dimethylformamide for 20 h (TLC
analyses). The reaction mixture was cooled and the deposited precipi-
tate was filtered off, washed with ethanol, dried, and crystallized from
appropriate solvent to produce 2a–e in a good yield. The filtrate was
concentrated and left overneight at 0◦C. A precipitate formed, was fil-
tered off, and crystallized from an appropriate solvent to afford 2ꢀa–e
in a low yield.
7-Phenyl-10-thioxo-5,6,10,11-tetrahydro-9H-benzo[h]-
pyrimido[4,5-b]quinolin-8-one (2a)
The compound (2a) was obtained from compound 1a (2.34, 10 mmol) as
a yellow powder and crystallized from dimethylformamide (61%), m.p.
369–371◦C; IR (KBr) cm−1: 3370 (brs, NH), 3047 (CH aryl), 2919 (CH
1
alkyl), 1688 (CO), 1615 (C N). H NMR (DMSO-d6) ppm: δ 2.43–2.46
(m, 2H, CH2), 2.72–2.88 (m, 2H, CH2), 7.16–7.19 (m, 2H, phenyl), 7.29–
7.31 (m, 1H, phenyl), 7.39–7.46 (m, 5H, phenyl + phenyl), 8.27–8.30 (m,
1H, phenyl) and 9.70, 11.20 (two NH, D2O exchangable). Its MS, [M+],
m/z 357 (100%). Analysis: C21H15N3OS (357.4). Requires: C, 70.57; H,
4.23; N, 11.75. Found: C, 70.47; H, 4.21; N, 11.69.
7-(4-Chloro-phenyl)-10-thioxo-5,6,10,11-tetrahydro-9H-
benzo[h]pyrimido[4,5-b]quinolin-8-one (2b)
The compound (2b) was obtained from compound 1b (2.68 g, 10 mmol)
as a yellow powder and crystallized from dimethylformamide (51%),
m.p. > 400◦C; IR (KBr) cm−1: 3345 (brs, NH), 3037 (CH aryl), 2920 (CH

1868
A. B. A. Elgazzar et al.
1
alkyl), 1687 (CO), 1608 (C N). H NMR (DMSO-d6) ppm: δ 2.50–2.53
(m, 2H, CH2), 2.76–2.79 (m, 2H, CH2), 6.97–6.99 (d, 2H, p-sub-pheny),
7.09–7.12 (d, 2H, phenyl), 7.29–7.41 (m, 1H, phenyl), 7.42–7.44 (m,
2H, phenyl), 8.26–8.30 (m, 1H, phenyl) and 12.17, 12.93 (two NH, D2O
exchangable). Its MS, [M+], m/z 391 (100%). Analysis: C21H14ClN3OS
(391.76). Requires: C, 64.36; H, 3.60; N, 10.73. Found: C, 64.35; H, 3.57;
N, 10.69.
7-(4-Bromo-phenyl)-10-thioxo-5,6,10,11-tetrahydro-9H-benzo-
[h]pyrimido[4,5-b]quinolin-8-one (2c)
The compound (2c) was obtained from compound 1c (3.13 g, 10 mmol)
as a pale yellow powder and crystallized from dimethylformamide
(53%), m.p. 397–399◦C; IR (KBr) cm−1: 3400 (brs, NH), 3019 (CH aryl),
2921 (CH alkyl), 1683 (CO), 1603(C N). 1H NMR (DMSO-d6) ppm:
δ 2.44–2.47 (m, 2H, CH2), 2.78–2.80 (m, 2H, CH2), 7.15–7.18 (d, 2H,
p-sub-pheny), 7.32–7.43 (m, 1H, phenyl), 7.43–7.45 (m, 2H, phenyl),
7.61–7.63 (d, 2H, phenyl), 8.26–8.30 (m, 1H, phenyl) and 12.25, 13.00
(two NH, D2O exchangable). Its MS, [M+], m/z 436 (100%). Analysis:
C21H14BrN3OS (436.3). Requires: C, 57.81; H, 3.23; N, 9.63. Found: C,
57.79; H, 3.19; N, 9.57.
7-(4-Methoxy-phenyl)-10-thioxo-5,6,10,11-tetrahydro-9H-
benzo[h]pyrimido[4,5-b]quinolin-8-one (2d)
The compound (2d) was obtained from compound 1d (2.64 g, 10 mmol)
as a pale yellow powder and crystallized from dimethylformamide
(57%), m.p. 361-363◦C; IR (KBr) cm−1: 3356 (brs, NH), 3021 (CH aryl),
1
2920 (CH alkyl), 1679 (CO), 1617 (C N). H NMR (DMSO-d6) ppm: δ
2.42–2.47 (m, 2H, CH2), 2.75–2.80 (m, 2H, CH2), 4.15 (s, 3H, OCH3)
7.18–7.22 (d, 2H, p-sub-pheny), 7.30–7.37 (m, 1H, phenyl), 7.44–7.47
(m, 2H, phenyl), 7.58–7.61 (d, 2H, phenyl), 8.32–8.38 (m, 1H, phenyl)
and 12.10, 12.60 (two NH, D2O exchangable). Its MS, [M+], m/z 387
(100%). Analysis: C22H17N3O2S (387.4). Requires: C, 68.20; H, 4.42; N,
10.85. Found: C, 68.18; H, 4.39; N, 10.81.
7-(2-Thienyl)-10-Thioxo-5,6,10,11-tetrahydro-9H-benzo[h]-
pyrimido[4,5-b]quinolin-8-one (2e)
The compound (2e) was obtained from compound 1e (2.72 g, 10 mmol)
as a yellow powder and crystallized from dimethylformamide (63%),
m.p. 334–336◦C; IR (KBr) cm−1: 3380 (brs, NH), 3038 (CH aryl), 2909
1
(CH alkyl), 1678 (CO), 1601 (C N). H NMR (DMSO-d6) ppm: δ 2.43–

Polynuclear Heterocyclic Derivatives
1869
2.48 (m, 2H, CH2), 2.68–2.79 (m, 2H, CH2), 7.14–7.17 (t, 1H, thiophene),
7.45–7.46 (d, 1H, disub-penyl), 7.47–7.78 (d, 1H, thiophene), 7.59–7.76
(m, 2H, phenyl), 8.24–8.27 (m, 2H , 1H for thiophene = 1H for phenyl),
12.41, 13.05 (two brs, 2NH, D2O exchangeable). Its MS, [M+], m/z 363
(100%). Analysis: C19H13N3OS2 (363.4.4). Requires: C, 62.79; H, 3.60;
N, 11.56. Found: C, 62.76; H, 3.56; N, 11.54.
7-(4-Chloro-phenyl)-10-methylthio-5,6,10,11-tetrahydro-9H-
benzo[h]pyrimido[4,5-b]quinolin-8-one (3)
To a warmed ethanolic potassium hydroxide solution (prepared by di-
solving 0.56 g, 10 mmol of potassium hydroxide in 50 mL of ethanol)
compound 2b (3.91 g, 10 mmol) was added, and heating was continued
for 30 min. The mixture was allowed to cool to r.t., and methyl iodide
(20 mmol) was added. The mixture was stirred under reflux for 5 h,
allowed to cool to r.t., and finally poured into cold water (100 mL). The
solid product precipitated was filtered off and washed with 100 mL of
water. The compound was obtained as pale white crystals, crystallized
from dioxane (87%), m.p. 313–315◦C (melted); IR (KBr) cm−1: 3403 (brs,
1
NH), 2950 (CH alkyl), 1676 (CO), 1580 (C N), 1500 (C C). H NMR
(DMSO-d6) ppm: δ 2.40–2.45 (m, 2H, CH2), 2.55 (s, 3H, SCH3), 2.65–
2.70 (m, 2H, CH2), 7.15–7.25 (d, 2H, phenyl), 7.30–7.35 (m, 1H, phenyl),
7.40–7.45 (m, 2H, phenyl), 7.45–7.55 (d, 2H, phenyl) 8.30–8.35 (m, 1H,
phenyl) and 12.50 (brs, NH, D2O exchangable). Its MS, [M+], m/z 405
(100%). Analysis: C22H16ClN3OS (405.9). Requires: C, 65.10; H, 3.97;
N, 10.35. Found: C, 65.08; H, 3.96; N, 10.32.
7-(4-Chlorophenyl)-10-hydrazino-5,6,10,11-tetrahydro-9H-
benzo[h]pyrimido[4,5-b]quinolin-8-one (4)
Method A
A suspention of dry compound 2b (3.91 g, 10 mmol) in hydrazine
hydrate (80–90%) (25 mL) was stirred under gentle reflux. The insol-
uble solid dissolved within 10 min with a copious evolution of methyl
mercaptan to form a clear solution. After 30 min when the solid prod-
uct started separating out, heating was continued for 8 h. The reaction
mixture was then allowed to cool to r.t. The solid was filtered, washed
with ethanol, dried, and crystallized from dimethylformamide (81%),
m.p. 307–309◦C.
Method B
A suspention of compound 3 (4.05, 10 mmol) and hydrazine hydrate
(99–100%, 25 mL) was stirred under reflux in dioxane (20 mL) for 12 h.

1870
A. B. A. Elgazzar et al.
The reaction mixture was allowed to cool to r.t. and poured into cold
water. The precipitate was filtered off, washed with water and ethanol,
and then dried and crystallized from dioxane (72%), yield, m.p. 306–
308◦C; IR (KBr) cm−1: 3365 (brs, NH), 2917 (CH alkyl), 1680 (CO).
1H NMR (DMSO-d6) ppm: δ 2.38–2.43 (m, 2H, CH2), 2.69–2.75 (m, 2H,
CH2), 7.09–7.15 (d, 2H, phenyl), 7.20–7.30 (m, 1H, phenyl), 7.34–7.38
(m, 2H, phenyl), 7.59–7.64 (d, 2H, phenyl) 8.30–8.35 (m, 1H, phenyl)
and 10.60, 11.85 (two brs, 2NH, D2O exchangable). Its MS, [M+], m/z
389 (100%). Analysis: C21H16ClN5O (389.8). Requires: C, 64.70; H, 4.14;
N, 17.97. Found: C, 64.67; H, 4.09; N, 17.95.
7-(4-Chloro-phenyl)-5,6-dihydro-9H-benzo[h]-1,2,4-triazolo-
[4ꢀ,3ꢀ:1,2]pyrimido[4,5-b]quinolin-8-one Derivatives (6a–f)
General Procedure
A mixture from compound 2b (3.91 g, 10 mmol) and the appropri-
ate hydrazonoyl chlorides 5a–f (10 mmol) was stirred under reflux in
dry chloroform (30 mL) and 4 drops of triethylamine for 5 h. The sol-
vent was evaporated under reduced pressure. The solid produced was
washed three times with 30 mL of methanol and crystallized form an
appropriate solvent to produce 6a–f in high yields.
7-(4-Chlorophenyl)-5,6-dihydro-9H-10,12-diphenyl-benzo[h]-
1,2,4-triazolo[4ꢀ,3ꢀ:1,2]-pyrimido[4,5-b]quinolin-8-one (6a)
Compound (6a) was obtained from the reaction of compound 2b (3.91 g,
10 mmol) and N-phenylbenzene-carbo-hydrazonoyl chloride 5a (2.31 g,
10 mmol) as a white needles and crystallized from dimethylformamide
(70%), m.p. 348–350◦C; IR (KBr) cm−1: 3046 (CH aryl), 2920 (CH alkyl),
1687 (CO), 1611 (C N), 1596 (C C). 1H NMR (DMSO-d6) ppm: δ 2.40–
2.45 (m, 2H, CH2), 2.75–2.85 (m, 2H, CH2), 7.20–7.25 (d, 2H, phenyl),
7.26–7.30 (m, 1H, phenyl), 7.40–7.52 (m, 8H, phenyl protons), 7.60–7.70
(m, 4H, phenyl protons), 8.30–8.35 (d, 2H, phenyl) and 8.40 (m, 1H,
phenyl). Its MS, [M+], m/z 552 (100%). Analysis: C34H22ClN5O (552.0).
Requires: C, 73.97; H, 4.02; N, 12.69. Found: C, 73.95; H, 4.00; N, 12.58.
10-Acetyl-7-(4-chlorophenyl)-5,6-dihydro-9H-12-
(4-chlorophenyl)-benzo[h]-1,2,4-triazolo[4ꢀ,3ꢀ:1,2]pyrimido-
[4,5-b]quinolin-8-one (6b)
Compound (6b) was obtained from the reaction of compound 2b (3.91
g, 10 mmol) and 2-oxo-N-(4-chlorophenyl)-propane hydrazonoyl chlo-
ride 5b (1.96 g, 10 mmol) as a brown powder and crystallized from

Polynuclear Heterocyclic Derivatives
1871
dimethylformamide (77%), m.p. 332–334◦C; IR (KBr) cm−1: 3032 (CH
1
aryl), 2923 (CH alkyl), 1682 (CO), 1580 (C N), 1556 (C C). H NMR
(DMSO-d6) ppm: δ 2.46–2.51 (m, 2H, CH2), 2.62 (s, 3H, CH3) 2.73–2.79
(m, 2H, CH2), 6.99–7.05 (d, 2H, p-subpheny), 7.10–7.15 (d, 2H, phenyl),
7.30–7.35 (m, 1H, phenyl), 7.42–7.44 (m, 2H, phenyl), 7.65–7.68 (d, 2H,
phenyl), 8.20–8.24 (d, 2H, phenyl) and 8.34–8.38 (m, 1H, phenyl). Its
MS, [M+], m/z 552 (100%). Analysis: C30H19Cl2N5O2 (552.4). Requires:
C, 65.22; H, 3.47; N, 12.65. Found: C, 65.18; H, 3.45; N, 12.59.
10-Acetyl-7-(4-chlorophenyl)-5,6-dihydro-9H-12-(4-methoxy-
phenyl)benzo[h]-1,2,4-triazolo[4ꢀ,3ꢀ:1,2]pyrimido[4,5-b]-
quinolin-8-one (6c)
Compound (6c) was obtained from the reaction of compound 2b (3.91 g,
10 mmol) and 2-oxo-N-(4-methoxyphenyl)-propane hydrazonoyl chlo-
ride 5c (1.91 g, 10 mmol) as a green powder and crystallized from
ethanol (68%), m.p. 273–275◦C; IR (KBr) cm−1: 3040 (CH aryl), 2918
1
(CH alkyl), 1687 (CO), 1600 (C N), 1587 (C C). H NMR (DMSO-d6)
ppm: δ 2.45–2.55 (m, 2H, CH2), 2.60 (s, 3H, CH3) 2.75–2.85 (m, 2H,
CH2), 3.85 (s, 3H, OCH3), 7.15–7.20 (d, 2H, p-subpheny), 7.20–7.25
(d, 2H, phenyl), 7.30–7.35 (m, 1H, phenyl), 7.45–7.55 (m, 2H, phenyl),
7.57–7.63 (d, 2H, phenyl), 8.00–8.05 (d, 2H, phenyl) and 8.30–8.35 (m,
1H, phenyl). Its MS, [M+], m/z 547 (100%). Analysis: C31H22ClN5O3
(547.98). Requires: C, 67.94; H, 4.05; N, 12.78. Found: C, 67.91; H, 4.06;
N, 12.69.
10-Acetyl-7-(4-chlorophenyl)-5,6-dihydro-9H-12-
(4-nitrophenyl)benzo[h]-1,2,4-triazolo-[4ꢀ,3ꢀ:1,2]pyrimido-
[4,5-b]quinolin-8-one (6d)
Compound (6d) was obtained from the reaction of compound 2b (3.91
g, 10 mmol) and 2-oxo-N-(4-nitrophenyl)-propane hydrazonoyl chloride
5d (2.06 g, 10 mmol) as a pale red crystals and crystallized from ethanol
(71%), m.p. 272–274◦C; IR (KBr) cm−1: 3045 (CH aryl), 2913 (CH alkyl),
1680 (CO), 1598 (C N), 1565 (C C). 1H NMR (DMSO-d6) ppm: δ 2.55–
2.60 (m, 2H, CH2), 2.80–2.90 (m, 2H, CH2) 2.95 (s, 3H, CH3), 7.15–7.20
(d, 2H, pheny), 7.25–7.35 (m, 1H, phenyl), 7.50–7.55 (m, 2H, phenyl),
7.56–7.60 (d, 2H, phenyl), 8.35–8.50 (m, 3H, one for disub, two for
phenyl) and 8.55–8.60 (d, 2H, phenyl). Its MS, [M+], m/z 562 (100%).
Analysis: C30H19ClN6O4 (562.9). Requires: C, 64.00; H, 3.40; N, 14.93.
Found: C, 64.02; H, 3.32; N, 14.88.

1872
A. B. A. Elgazzar et al.
7-(4-Chlorophenyl)-5,6-dihydro-9H-10-ethylcarboxylate-12-
phenyl-benzo[h]-1,2,4-triazolo-[4ꢀ,3ꢀ:1,2]pyrimido[4,5-
b]quinolin-8 one (6e)
Compound (6e) was obtained from the reaction of compound 2b (3.91
g, 10 mmol) and chloro(phenylhydrazono)-ethylacetate 5e (2.27 g, 10
mmol) as a white powder and crystallized from dimethylformamide
(70%), m.p. 278–279◦C; IR (KBr) cm−1: 3039 (CH aryl), 2913 (CH
1
aliphatic), 1689 (CO), 1588 (C N), 1553 (C C). H NMR (DMSO-d6)
ppm: δ 1.25 (t, 3H, CH3), 2.35–2.45 (m, 2H, CH2), 2.65–2.80 (m, 2H,
CH2) 4.40 (q, 2H, CH2), 7.25–7.30 (d, 2H, p-subpheny), 7.31–7.35 (m,
1H, phenyl), 7.40-7.75 (m, 7H, 5H (phenyl) + 2H (phenyl), 8.05–8.10
(d, 2H, phenyl) and 8.30–8.35 (d, 1H, phenyl). Its MS, [M+], m/z 547
(100%). Analysis: C31H22ClN5O3 (547.9). Requires: C, 67.94; H, 4.05; N,
12.78. Found: C, 67.89; H, 4.07; N, 12.69.
7-(4-Chlorophenyl)-5,6-dihydro-9H-10-ethylcarboxylate-12-
(4-methylphenyl)benzo[h]-1,2,4-triazolo[4ꢀ,3ꢀ:1,2]-
pyrimido[4,5-b]quinolin-8-one (6f)
Compound (6f) was obtained from the reaction of compound 2b (3.91
g, 10 mmol) and chloro(4-tolylhydrazono)-ethylacetate 5f (2.41 g, 10
mmol) as a yellow powder and crystallized from ethanol/dioxane (60%),
m.p. 316–319◦C (dec.); IR (KBr) cm−1: 3029 (CH aryl), 2923 (CH
1
aliphatic), 1685 (CO), 1596 (C N), 1543 (C C). H NMR (DMSO-d6)
ppm: δ 1.28 (t, 3H, CH3), 2.35 (s, 3H, CH3), 2.40–2.45 (m, 2H, CH2),
2.75–2.85 (m, 2H, CH2) 4.38 (q, 2H, CH2), 7.25–7.35 (m, 3H, 2H p-
subpheny + 1H phenyl), 7.40–7.55 (m, 4H, 2H for phenyl + 2H phenyl),
8.00–8.05 (d, 2H, phenyl) and 8.35–8.45 (m, 1H, phenyl). Its MS, [M+],
m/z 562 (100%). Analysis: C32H24ClN5O3 (562.0). Requires: C, 68.38; H,
4.30; N, 12.46. Found: C, 68.34; H, 4.23; N, 12.39.
7-(4-Chlorophenyl)-5,6-dihydro-9H-benzo[h]-1,2,4-zriazolo-
[4ꢀ,3ꢀ:1,2]pyrimido[4,5-b]-quinolin-8-one (7a)
A mixture of compound 4 (3.89 g, 10 mmol), formic acid (10 mL), and cat-
alytic amount of concentrated hydrochloric acid was heated under reflux
for 6 h. The reaction mixture was allowed to cool to r.t. and was poured
into water (100 mL). The formed solid was collected by filtration, washed
with ethanol (20 mL), dried, and crystallized from dimethylformamide
(75%), m.p. 382–385 ◦C; IR (KBr) cm−1: 3350 (brs, NH), 2980 (CH alkyl),
1685 (CO), 1580 (C N), 1500 (C C). 1H NMR (DMSO-d6) ppm: δ 2.52–
2.60 (m, 2H, CH2), 2.75–2.85 (m, 2H, CH2), 7.20–7.25 (d, 2H, phenyl),

Polynuclear Heterocyclic Derivatives
1873
7.27–7.33 (m, 1H, phenyl), 7.40–7.45 (m, 2H, phenyl), 7.50–7.55 (d, 2H,
phenyl) 8.50–8.55 (m, 1H, phenyl), 9.50 (s, 1H, H triazole) and 12.65
(brs, 1H, NH, D2O exchangable). Its MS, [M+], m/z 399 (100%). Analy-
sis: C22H14ClN5O (399.8). Requires: C, 66.08; H, 3.53; N, 17.52. Found:
C, 66.10; H, 3.49; N, 17.43.
7-(4-Chlorophenyl)-5,6-dihydro-9H-10-methyl-benzo[h]-1,2,4-
triazolo[4ꢀ,3ꢀ:1,2]pyrimido-[4,5-b]quinolin-8-one (7b)
A mixture of 4 (3.89 g, 10 mmol) and glacial acetic acid (30 mL) was
stirred under reflux for 6 h (under TLC analysis). The reaction mixture
was allowed to cool to r.t. and was poured into water (100 mL). The solid
formed was collected by filtration, washed with ethanol (20 mL), dried,
and crystallized from dimethylformamide (70%), m.p. 370◦C (dec.); IR
(KBr) cm−1: 3316 (brs, NH), 2986 (CH alkyl), 1678 (CO), 1583 (C N),
1507 (C C). 1H NMR (DMSO-d6) ppm: δ 2.45–2.55 (m, 2H, CH2),
2.70–2.85 (m, 2H, CH2), 3.05 (s, 3H, CH3), 7.15–7.20 (d, 2H, phenyl),
7.25–7.30 (m, 1H, phenyl), 7.35–7.45 (m, 2H, phenyl), 7.50–7.55 (d,
2H, phenyl) 8.20–8.25 (m, 1H, phenyl) and 12.55 (brs, 1H, NH, D2O
exchangable). Its MS, [M+], m/z 413 (100%). Analysis: C23H16ClN5O
(413.8). Requires: C, 66.75; H, 3.90; N, 16.92. Found: C, 66.78; H, 3.88;
N, 16.87.
7-(4-Chlorophenyl)-10-acethydrazido)-5,6,10,11-tetrahydro-
9H-benzo[h]pyrimido[4,5-b]-quinolin-8-one (8)
A solution of compound 4 (3.89 g, 10 mmol) in glacial acetic acid was
refluxed for 3 h. The reaction mixture was then allowed to cool to r.t. and
was poured into cold water (100 mL); the solid formed was collected by
filtration, dried, and crystallized from ethanol (47%), m.p. 350◦C (dec.):
IR (KBr) cm−1: 3389, 3100 (brs, 2NH), 2922 (CH alkyl), 1709 (CO),
1686 (CO), 1612 (C N). Its MS, [M+], m/z 431 (100%). Analysis: C23H18
ClN5O2 (431.8). Requires: C, 63.96; H, 4.20; N, 16.22. Found: C, 63.89;
H, 4.17; N, 16.14.
10-Amino-7-(4-chlorophenyl)-5,6-dihydro-9H-benzo[h]-1,2,4-
triazolo[4ꢀ,3ꢀ:1,2]pyrimido-[4,5-b]quinolin-8-one (9)
A mixture of compound 4 (3.89 g, 10 mmol) and potassium thiocyanate
(0.97 g, 10 mmol) was heated under reflux in acetic acid for 6 h. The
reaction mixture was allowed to cool to r.t. and was poured into water.
The precipitate formed was collected by filtration, dried, and crystal-
lized from dimethylformamide to produce a white powder (67%), m.p.

1874
A. B. A. Elgazzar et al.
1
402–403◦C. IR spectrum (KBr) cm−1: 3412 (NH) and 1678 (CO). H
NMR (DMSO-d6) ppm: δ 2.43 (brs, 2H, NH2, D2O exchangable), 2.50–
2.56 (m, 2H, CH2), 2.73–2.88 (m, 2H, CH2), 3.31 (brs, 1H, NH, D2O ex-
changable), 7.20–7.24 (d, 2H, phenyl), 7.33–7.36 (m, 1H, phenyl), 7.46–
7.49 (m, 2H, phenyl), 7.50–7.52 (d, 2H, phenyl) and 8.28–8.31 (m, 1H,
phenyl). Its MS, [M+], m/z 414 (100%). Analysis: C22H15ClN6O (414.8).
Requires: C, 63.69; H, 3.64; N, 20.26. Found: C, 63.64; H, 3.59; N, 20.14.
7-(4-Chlorophenyl)-5,6-dihydro-9H-10-thioxo-benzo[h]-1,2,4-
triazolo[4ꢀ,3ꢀ:1,2]pyrimido[4,5-b]quinolin-8-one (10)
To a warmed ethanolic sodium hydroxide solution (prepared by dissolv-
ing (0.40 g, 10 mmol) sodium hydroxide in ethanol (50 mL) (3.89 g,
10 mmol) of compound 4b and excess carbon disulphide (10 mL) was
added. The mixture was heated on a waterbath at 80◦C under reflux
for 10 h, then allowed to cool to r.t. poured into water (100 mL), and
neutralized by dilute acetic acid; the formed precipitate was filtered
off and dried. The product was crystallized from benzene (65%), m.p.
349–350◦C; IR (KBr) cm−1: 3465 (brs, NH), 2933 (CH alkyl), 1686 (CO),
1
1625 (C N), 1530 (C C), H NMR (DMSO-d6) ppm: δ 2.40–2.55 (m,
2H, CH2), 2.80–3.00 (m, 2H, CH2), 7.15–7.25 (d, 2H, phenyl), 7.30–7.40
(m, 1H, phenyl), 7.45–7.50 (m, 2H, phenyl), 7.51–7.55 (d, 2H, phenyl),
8.75–8.80 (m, 1H, phenyl) and 12.55 (brs, 1H, NH, D2O exchangable),
13.65 (brs, 1H, NH, D2O exchangable). Its MS, [M+], m/z 431 (100%).
Analysis: C22H14ClN5OS (431.8). Requires: C, 61.18; H, 3.27; N, 16.22.
Found: C, 61.13; H, 3.24; N, 16.19.
10-(3-Amino-5-hydroxy-4H-pyrazol-5-one-1-yl)-7-
(4-chlorophenyl)-5,6,10,11-tetrahydro-9H-benzo[h]pyrimido-
[4,5-b]quinolin-8-one (11)
To a warmed ethanolic sodium ethoxide solution (prepared by dissolving
(0.23 g, 10 mmol) sodium metal in absolute ethanol (30 mL)) each of
compound 4b (3.89 g, 10 mmol) and ethylcyanoacetate (1.13 g, 10 mmol)
was added. The mixture was stirred under reflux for 8 h. The reaction
mixture was allowed to cool to r.t. poured into cold water (100 mL),
and neutralized with acetic acid. The solid product precipitated was
filtered off, washed with water and ethanol, dried, and crystallized from
dioxane (56%), m.p. 280–282◦C (dec.); IR (KBr) cm−1: 3318 (brs, NH),
2921 (CH alkyl), 1687 (CO), 1601 (C N), 1520 (C C). 1H NMR (DMSO-
d6) ppm: δ 2.36–2.43 (m, 2H, CH2), 2.67–2.75 (m, 2H, CH2), 3.57 (s, 2H,
CH2), 7.17–7.25 (d, 2H, phenyl), 7.27–7.34 (m, 1H, phenyl), 7.43–7.50

Polynuclear Heterocyclic Derivatives
1875
(m, 2H, phenyl), 7.53–7.58 (d, 2H, phenyl), 8.41–8.43 (m, 1H, phenyl)
and 12.20, 12.85 (2 brs, NH, D2O exchangable). Its MS, [M+], m/z 456
(100%). Analysis: C24H17ClN6O2 (456.8). Requires: C, 63.09; H, 3.75; N,
18.40. Found: C, 63.07; H, 3.71; N, 18.36.
7-(4-Chlorophenyl)-10-(ethylacetoacetatehydrazone)-5,6,10,11-
tetrahydro-9H-benzo[h]pyrimido[4,5-b]quinolin-8-one (12)
A mixture of compound 4b (3.89 g, 10 mmol) and ethylacetoacetate (1.30
g, 10 mmol) was refluxed in absolute ethanol (30 mL) for 5 h. The reac-
tion mixture was allowed to cool to r.t. and the solid precipitate produced
was filtered off and crystallized from ethanol to produce a pale brown
powder (87%), m.p. 201–203◦C; IR (KBr) cm−1: 3250 (brs, NH), 2942 (CH
1
alkyl), 1740, 1680 (2CO), 1580 (C N), 1500 (C C), H NMR (DMSO-
d6) ppm: δ 1.25 (t, 3H, CH3), 2.00 (s, 3H, CH3), 2.35–2.45 (m, 2H, CH2),
2.70–2.85 (m, 2H, CH2), 3.35 (s, 2H, CH2), 4.15 (q, 2H, CH2), 7.15–7.25
(d, 2H, phenyl), 7.25–7.30 (m, 1H, phenyl), 7.30–7.35 (m, 2H, phenyl),
7.40–7.50 (d, 2H, phenyl), 8.20–8.30 (m, 1H, phenyl), 9.80–10.40 (brs,
1H, NH, D2O exchangable) and 11.15 (brs, NH, D2O exchangable). Its
MS, [M+], m/z 501 (100%). Analysis: C27H24ClN5O3 (501.9). Requires:
C, 64.60; H, 4.82; N, 13.95. Found: C, 64.56; H, 4.79; N, 13.92.
7-(4-Chlorophenyl)-10-(3-methyl-4H-pyrazol-5-one-1-yl)-
5,6,10,11-tetrahydro-9H-benzo[h]pyrimido[4,5-b]quinolin-
8-one (13)
Method A
A solution of compound 4b (3.89 g, 10 mmol) and ethylacetoacetate
(1.30 g, 10 mmol) in sodium ethoxide solution (prepared by dissolving
0.23 g, 10 mmol of sodium metal in absolute ethanol (30 mL) was heated
under reflux with stirring for 6 h. The reaction mixture was allowed to
cool, poured into cold water (100 mL) and neutralized by acetic acid,
whereby a solid was precipitated, which was filtered off and crystallized
from dimethylformamide to produce a white powder (61%), m.p. 356–
358◦C (dec.).
Method B
A solution of compound 12 (5.02 g, 10 mmol) was heated under reflux
with sodium ethoxide solution (0.23 g, 10 mmol) of sodium metal in ab-
solute ethanol (30 mL) for 3 h. The reaction mixture was allowed to cool,
poured into water (100 mL) and neutralized by acetic acid; the precip-
itate formed was filtered off and crystallized from dimethylformamide

1876
A. B. A. Elgazzar et al.
(72%). IR (KBr) cm−1: 3400 (brs, NH), 2936 (CH alkyl), 1698, 1684
(2CO), 1550 (C N), 1500 (C C), 1H NMR (DMSO-d6) ppm: δ 2.35–2.45
(m, 2H, CH2), 2.50 (s, 3H, CH3), 2.65–2.75 (m, 2H, CH2), 3.45 (s, 2H,
CH2), (7.15–7.25 (d, 2H, phenyl), 7.25–7.30 (m, 1H, phenyl), 7.35–7.40
(m, 2H, phenyl), 7.45–7.50 (d, 2H, phenyl), 8.35–8.45 (m, 1H, phenyl)
and 14.3 (brs, NH, D2O exchangable). Its MS, [M+], m/z 455 (100%).
Analysis: C25H18ClN5O2 (455.8). Requires: C, 65.86; H, 3.98; N, 15.36.
Found: C, 65.64; H, 3.89; N, 15.29.
7-(4-Chlorophenyl)-10-(3-methyl-4-phenylazo-pyrazol-5-one-1-
yl)-5,6,10,11-tetrahydro-9H-benzo[h]pyrimido[4,5-b]-
quinolin-8-one (14)
To an ice-cold solution of the appropriate aromatic amine (10 mmol) in
concentrated hydrochloric acid (3 mL) was added dropwise a solution
of sodium nitrite (1.03 g, 0.01 mole) dissolved in the least amount of
water in an ice bath at −5◦C. This previously prepared diazonium salt
was added dropwise to a mixture of 13 (4.56 g, 10 mmol) and anhydrous
sodium acetate in ethanol. The reaction mixture was allowed to stand
over night at r.t. and then it was poured into water. The formed solid was
filtered off and washed with water. The product was recrystallized from
dioxane to produce a brown powder (47%), m.p. 269–270◦C. IR spectrum
(KBr) cm−1: 3436 (OH), 3250 (NH), 2917 (CH aliphatic) and 1686 (CO).
1H NMR (DMSO-d6) ppm: δ 2.41 (s, 3H, CH3), 2.49–2.54 (m, 2H, CH2),
2.80–2.85 (m, 2H, CH2), 7.19–7.21 (m, 1H, phenyl), 7.25–7.28 (d, 2H,
phenyl), 7.30–7.36 (m, 1H, phenyl), 7.38–7.47 (m, 6H, 2H phenyl + 4H
phenyl), 7.49–7.56 (d, 2H, phenyl), 8.40–8.41 (m, 1H, phenyl) and 11.20
(brs, NH, D2O exchangable). Its MS, [M+], m/z 560 (100%). Analysis:
C31H22ClN7O2 (560.0). Requires: C, 66.48; H, 3.96; N, 17.51. Found: C,
66.48; H, 3.87; N, 17.46.
7-(4-Chloro-phenyl)-10-(3-methyl-4-(un)substituted-5-
substituted Pyrazol-1-yl)-5,6,10,11-tetrahydro-9H-
benzo[h]pyrimido[4,5-b]-quinolin-8-one (15a–c)
General Procedure
A mixture of compound 4b (3.89 g, 10 mmol and 10 mmol) of either
β-diketone in absolute ethanol (30 mL) was stirred under reflux for 5 h.
The reaction mixture was allowed to cool to 0◦C for 3 h, the deposited
precipitate was filtered off, dried, and crystallized from the appropriate
solvent to produce 15a–c in high yields.

Polynuclear Heterocyclic Derivatives
1877
7-(4-Chlorophenyl)-10-(3,5-dimethyl-4H-pyrazol-1-yl)-5,6,10,11-
tetrahydro-9H-benzo[h]-pyrimido[4,5-b]quinolin-8-one (15a)
Compound 4b (3.89 g, 10 mmol) and pentan-2,4-dione (1.00 g, 10 mmol).
The compound was obtained as a pale light crystals and crystallized
from dimethylformamide (70%), m.p. 356–358◦C; IR (KBr) cm−1: 3320
(brs, NH), 3054 (CH aryl), 2943 (CH alkyl), 1693 (CO), 1600 (C N),
1
1550 (C C), H NMR (DMSO-d6) ppm: δ 2.25 (s, 3H, CH3), 2.45–2.55
(m, 2H, CH2), 2.65 (s, 3H, CH3), 2.70–2.85 (m, 2H, CH2), 6.40 (s, 1H,
pyrazol proton), 7.20–7.25 (d, 2H, phenyl), 7.27–7.35 (m, 1H, phenyl),
7.45–7.50 (m, 2H, phenyl), 7.52–7.57 (d, 2H, phenyl), 8.35–8.40 (m, 1H,
phenyl) and 11.90, (brs, NH, D2O exchangable). Its MS, [M+], m/z 453
(100%). Analysis: C26H20ClN5O (453.9). Requires: C, 68.79; H, 4.44; N,
15.43. Found: C, 68.76; H, 4.38; N, 15.37.
7-(4-Chlorophenyl)-10-(3,5-dimethyl-4-chloropyrazol-1-yl)-
5,6,10,11-tetrahydro-9H-benzo-[h]pyrimido[4,5-b]quinolin-
8-one (15b)
Compound 4b (3.89 g, 10 mmol) and 3-chloropentan-2,4-dione (1.34
g, 10 mmol). The compound was obtained as light white crystals and
crystallized from ethanol (68%), m.p. 309–312◦C; IR (KBr) cm−1: 3230
1
(brs, NH), 2953 (CH alkyl), 1685 (CO), 1609 (C N), 1576 (C C), H
NMR (DMSO-d6) ppm: δ 2.25 (s, 3H, CH3), 2.50–2.55 (m, 2H, CH2),
2.65 (s, 3H, CH3), 2.70–2.85 (m, 2H, CH2), 7.20–7.25 (d, 2H, phenyl),
7.27–7.35 (m, 1H, phenyl), 7.40–7.45 (m, 2H, phenyl), 7.50–7.55 (d,
2H, phenyl), 8.30–8.35 (m, 1H, phenyl), and 12.10, (brs, NH, D2O ex-
changable). Its MS, [M+], m/z 488 (100%). Analysis: C26H19Cl2N5O
(488.3). Requires: C, 63.94; H, 3.92; N, 14.34. Found: C, 63.87; H, 3.90;
N, 14.31.
7-(4-Chlorophenyl)-10-(3-methyl,4H-50trifluromethylpyrazol-
1-yl) 5,6,10,11-tetrahydro-9H-benzo[h]pyrimido[4,5-
b]quinolin-8-one (15c)
Compound 4b (3.89 g, 10 mmol) and 1,1,1-trifluro-2,4-pentandione (1.54
g, 10 mmol). The compound was obtained as pale light colorless crystals
and crystallized from ethanol (56%), m.p. 244–246◦C; IR (KBr) cm−1
:
3260 (brs, NH), 2935 (CH alkyl), 1689 (CO), 1600 (C N), 1554 (C C),1H
NMR (DMSO-d6) ppm: δ 2.10 (s, 3H, CH3), 2.45–2.55 (m, 2H, CH2),
2.75–2.85 (m, 2H, CH2), 7.15–7.20 (d, 2H, phenyl), 7.21–7.25 (m, 1H,
phenyl), 7.40–7.48 (m, 2H, phenyl), 7.50–7.55 (d, 2H, phenyl), 8.30–8.40
(m, 1H, phenyl), 8.75 (s, 1H, pyrazol proton) and 11.40 (brs, NH, D2O

1878
A. B. A. Elgazzar et al.
exchangable). Its MS, [M+], m/z 507 (100%). Analysis: C26H17ClF3N5O
(507.8). Requires: C, 61.48; H, 3.37; N, 13.79. Found: C, 61.46; H, 3.29;
N, 13.52.
7-(4-Chlorophenyl)-5,6,12-trihydro-9H-benzo[h]tetrazolo[4ꢀ,5ꢀ:
1,2]pyrimido[4,5-b]quinolin-8-one (16)
To an ice-cold solution of compound 4b (3.89 g, 10 mmol) in acetic acid
(10 mL) was added dropwisely a solution of sodium nitrite (1.04 g, 15
mmol) in the least amount of water in an ice bath at −5◦C. The re-
action mixture was allowed to stand overnight at r.t. and then it was
poured into water (100 mL). The solid precipitated was filtered off and
crystallized from dixane to produced pale yellow powder (54%), m.p.
269–270◦C; IR (KBr) cm−1: 3243 (brs, NH), 2934 (CH alkyl), 1700 (CO),
1629 (N N), 1582 (C N), 1506 (C C), 1H NMR (DMSO-d6) ppm: δ 2.45–
2.50 (m, 2H, CH2), 2.80–2.90 (m, 2H, CH2), 7.20–7.25 (d, 2H, phenyl),
7.27–7.31 (m, 1H, phenyl), 7.40–7.60 (m, 4H, 2H phenyl + 2H phenyl),
8.25–8.35 (m, 1H, phenyl), and 13.25, (brs, NH, D2O exchangable). Its
MS, [M+], m/z 400 (100%). Analysis: C21H13ClN6O (400.8). Requires: C,
62.92; H, 3.27; N, 20.97. Found: C, 62.89; H, 3.21; N, 20.78.
10-Amino-7-(4-chlorophenyl)-5,6,10,11-tetrahydro-9H-
benzo[h]-pyrimido[4,5-b]quinolin-8-one (17)
To a well-stirred solution the appropriate tetrazolothienopyrimidine 16
(4.01 g, 10 mmol) in glacial acetic acid (30 mL) was added protionwise
activated zinc dust (10.00 g) at r.t. over a period of 30 min. Stirring
was continued for an additional 3 h. Thereafter, the reaction mixture
was heated on a waterbath (80–90◦C) for 3 h. The progress of reduc-
tion was monitored by TLC. After allowing the reaction mixture to cool
to r.t. it was poured into cold water (100 mL). The insoluble solid that
separated was filterd, washed with water, and dried. The crude solid
was extracted with hot benzene and the solid obtained after the re-
movel of benzene under reduced pressure was crystallized from dioxane
(72%), m.p. 286–288◦C; IR (KBr) cm−1: 3310 (brs, NH2), 2910 (CH alkyl),
1687 (CO), 1589 (C N), 1551 (C C), 1H NMR (DMSO-d6) ppm: δ 2.30–
2.40 (m, 2H, CH2), 2.80–2.90 (m, 2H, CH2), 3.55–3.60 (brs, 2H, NH2
D2O exchangable), 4.45 (brs, NH, D2O exchangable), 7.15–7.30 (m, 1H,
phenyl), 7.35–7.40 (d, 2H, phenyl), 7.45–7.50 (m, 3H, 2H phenyl + 1H
phenyl) and 7.70–7.75 (m, 1H, phenyl). Its MS, [M+], m/z 374 (100%).
Analysis: C21H15ClN4O (374.8). Requires: C, 67.29; H, 4.03; N, 14.95.
Found: C, 67.23; H, 4.00; N, 14.86.

Polynuclear Heterocyclic Derivatives
1879
7-(4-Chlorophenyl)-10-(arylmethylenehydrazone)-5,6,10,11-
tetrahydro-9H-benzo[h]-pyrimido[4,5-b]quinolin-8-one
(18a–c)
General Procedure
A mixture from compound 4b (3.89 g, 10 mmol), the appropriate
aromatic aldehyde (10 mmol), and anhydrous sodium acetate (1.64 g,
20 mmol) was stirred under reflux in glacial acetic acid (30 mL) for
5 h. The reaction mixture was allowed to cool to r.t. and was poured
into water (100 mL), whereby a solid was filtered off and crystallized
from an appropriate solvent to produce 18a–c in high yields.
7-(4-Chlorophenyl)-10-(phenylmethylenehydrazone)-5,6,10,11-
tetrahydro-9H-benzo[h]-pyrimido[4,5-b]quinolin-8-one (18a)
Compound 4 (3.89 g, 10 mmol) and benzaldehyde (1.06 g, 10 mmol).
The compound was obtained as yellow crystals and crystallized from
dimethylformamide (63%), m.p. 337–339◦C (melted); IR (KBr) cm−1
:
3250 (brs, NH), 3040 (CH aryl), 2920 (CH alkyl), 1670 (CO), 1600 (C N),
1500 (C C), 1H NMR (DMSO-d6) ppm: δ 2.35–2.50 (m, 2H, CH2), 2.65–
2.75 (m, 2H, CH2), 7.10–7.15 (d, 2H, phenyl), 7.16–7.20 (m, 1H, phenyl),
7.35–7.50 (m, 5H, 2H phenyl + 3H phenyl), 7.90–7.95 (d, 2H, phenyl),
7.96–8.05 (s, 1H, methylenic proton) 8.35–8.40 (m, 1H, phenyl), 11.20
(brs, NH, D2O exchangable) and 11.60 (brs, NH, D2O exchangable). Its
MS, [M+], m/z 477 (100%). Analysis: C28H20ClN5O (477.9). Requires:
C, 70.63; H, 4.22; N, 14.65. Found: C, 70.58; H, 4.19; N, 14.54.
7-(4-Chlorophenyl)-10-(4-chlorophenyllmethylenehydrazone)-
5,6,10,11-tetrahydro-9H-benzo[h]pyrimido[4,5-b]quinolin-8-
one (18b)
Compound 4 (3.89 g, 10 mmol) and 4-chlorobenzaldehyde (1.40 g,
10 mmol). The compound was obtained as pale yellow crystals and
crystallized from dimethylformamide (67%) yield, m.p. 349–351◦C; IR
(KBr) cm−1: 3368 (brs, NH), 3044 (CH aryl), 2916 (CH alkyl), 1676 (CO),
1605 (C N), 1517 (C C), 1H NMR (DMSO-d6) ppm: δ 2.40–2.50 (m, 2H,
CH2), 2.75–2.85 (m, 2H, CH2), 7.20–7.25 (d, 2H, phenyl), 7.26–7.30 (m,
1H, phenyl), 7.40–7.45 (m, 2H, phenyl), 7.46–7.53 (2d, 4H, phenyl),
7.95–8.05 (d, 2H, phenyl) 8.10–8.15 (s, 1H, methylenic proton), 8.30–
8.40 (m, 1H, phenyl) and 11.35 (brs, NH, D2O exchangable). Analysis:
C28H19ClN5O (512.3). Requires: C, 65.63; H, 3.74; N, 13.67. Found: C,
65.56; H, 3.67; N, 13.53.

1880
A. B. A. Elgazzar et al.
7-(4-Chlorophenyl)-10-(4-methoxyphenylmethyl-
enehydrazone)-5,6,10,11-tetrahydro-9H-benzo
[h]pyrimido[4,5-b]quinolin-8-one (18c)
Compound 4 (3.89 g, 10 mmol) and 4-methoxybenzaldehyde (1.36 g, 10
mmol). The compound was obtained as yellow powder and crystallized
from dimethylformamide (72%), m.p. 329–330◦C; IR (KBr) cm−1: 3368
(brs, NH), 3044 (CH aryl), 2916 (CH alkyl), 1676 (CO), 1605 (C N), 1517
(C C), 1H NMR (DMSO-d6) ppm: δ 2.45–2.50 (m, 2H, CH2), 2.75–2.85
(m, 2H, CH2), 3.85 (s, 3H, OCH3), 6.95–7.05 (d, 2H, phenyl), 7.20–7.25
(d, 2H, phenyl), 7.26–7.30 (m, 1H, phenyl), 7.40–7.45 (m, 2H, phenyl),
7.47–7.50 (d, 2H, phenyl), 7.85–7.95 (d, 2H, phenyl) 8.05–8.11 (s, 1H,
methylenic proton), 8.30–8.40 (m, 1H, phenyl) and 11.20 (brs, NH, D2O
exchangable). Its MS, [M+], m/z 507 (100%). Analysis: C29H22ClN5O2
(507.9). Requires: C, 68.57; H, 4.36; N, 13.79. Found: C, 68.53; H, 4.35;
N, 13.69.
10-Aryl-7-(4-chloro-phenyl)-5,6-dihydro-9H-benzo[h]-1,2,4-
triazolo[4ꢀ,3ꢀ:1,2]pyrimido[4,5-b]quinolin-8-one (19a-c)
General Procedure
A mixture of compound (18a–c) (10 mmol), anhydrous sodium acetate
(1.64 g, 20 mmol), and bromine (1.60 g, 10 mmol) was heated gently in
glacial acetic acid (30 mL) in a wasterbath at 80◦C for a long time
(under TLC control). The reaction mixture was allowed to cool to r.t.
and was poured into water (100 mL) and the solid formed was collected
by filtration and crystallized from an appropriate solvent to produce
19a–c.
7-(4-Chloro-phenyl)-5,6-dihydro-9H-10-phenyl-benzo[h]-1,2,4-
Triazolo[4ꢀ,3ꢀ:1,2]pyrimido-[4,5-b]quinolin-8-one (19a)
Compound (19a) was obtained from the reaction of compound 18a (4.78
g, 10 mmol) as a dark yellow powder and crystallized from dimethylfor-
mamide (62%), m.p. 328–330◦C (dec.); IR (KBr) cm−1: 3290 (brs, NH),
3039 (CH aryl), 2919 (CH alkyl), 1693 (CO), 1563 (C N), 1506 (C C).
1H NMR (DMSO-d6) ppm: δ 2.37–2.50 (m, 2H, CH2), 2.68–2.76 (m, 2H,
CH2), 7.09–7.15 (d, 2H, phenyl), 7.18–7.22 (m, 1H, phenyl), 7.34–7.47
(m, 5H, 2H phenyl + 3H phenyl), 7.96–8.06 (d, 2H, phenyl), 8.33–8.40
(m, 1H, phenyl) and 11.16 (brs, NH, D2O exchangable). Its MS, [M+],
m/z 475 (100%). Analysis: C28H18ClN5O (475.9). Requires: C, 70.66; H,
3.81; N, 14.72. Found: C, 70.56; H, 3.73; N, 14.53.

Polynuclear Heterocyclic Derivatives
1881
7,10-Di(4-chlorophenyl)-5,6-dihydro-9H-10-benzo[h]-1,2,4-Tri-
azolo[4ꢀ,3ꢀ:1,2]pyrimido-[4,5-b]quinolin-8-one (19b)
Compound (19b) was obtained from the reaction of compound 18b (5.12
g, 10 mmol) as brown crystals and crystallized from dimethylformamide
(61%), m.p. 359◦C (dec.); IR (KBr) cm−1: 3287 (brs, NH), 3052 (CH aryl),
2920 (CH alkyl), 1693 (CO), 1606 (C N), 1559 (C C), 1H NMR (DMSO-
d6) ppm: δ 2.43–2.50 (m, 2H, CH2), 2.75–2.83 (m, 2H, CH2), 7.15–7.20
(d, 2H, phenyl), 7.25–7.30 (m, 1H, phenyl), 7.35–7.45 (m, 2H, phenyl),
7.45–7.55 (2d, 4H, phenyl), 7.98–8.15 (d, 2H, phenyl), 8.29–8.38 (m, 1H,
phenyl) and 11.65 (brs, NH, D2O exchangable). Its MS, [M+], m/z 330
(100%). Analysis: C28H17Cl2N5O (330.8). Requires: C, 65.89; H, 3.36; N,
13.72. Found: C, 65.81; H, 3.29; N, 13.59.
7-(4-Chlorophenyl)-5,6-dihydro-9H-10-(4-methoxyphenyl)-
benzo[h]-1,2,4-triazolo-[4ꢀ,3ꢀ:1,2]pyrimido[4,5-b]quinolin-8-
one (19c)
Compound (19c) was obtained from the reaction of compound 18c (5.08
g, 10 mmol) as light yellow powder and crystallized from dimethylfor-
mamide (65%), m.p. 343–346◦C; IR (KBr) cm−1: 3290 (brs, NH), 3053
1
(CH aryl), 2918 (CH alkyl), 1689 (CO), 1549 (C N), 1499 (C C). H
NMR (DMSO-d6) ppm: δ 2.40–2.50 (m, 2H, CH2), 2.75–2.80 (m, 2H,
CH2), 3.89 (s, 3H, OCH3), 6.97–7.08 (d, 2H, phenyl), 7.17–7.25 (d,
2H, phenyl), 7.25–7.30 (m, 1H, phenyl), 7.37–7.46 (m, 2H, phenyl),
7.50–7.55 (d, 2H, phenyl), 7.85–8.00 (d, 2H, phenyl), 8.34–8.40 (m, 1H,
phenyl) and 11.42 (brs, NH, D2O exchangable). 13C NMR (DMSO-d6)
ppm: δ 24.42, 26.44 (2CH2, SP3), 56.83 (OCH3 SP3), 109.6, 110.5, 112.2,
122.2, 126.2, 126.8, 128.1, 128.3, 129.4, 130.1, 130.6, 131.0, 131.5, 132.1,
132.3, 134.7, 136.3, 139.3, 144.9, 151.2, 154.0, 157.0 (SP2) 159.0 (CO).
Its MS, [M+], m/z 505 (100%). Analysis: C29H20ClN5O2 (505.94). Re-
quires: C, 68.84; H, 3.98; N, 13.84. Found: C, 68.79; H, 3.94; N, 13.68.
7-(4-Chlorophenyl)-5,6-dihydro-9H-11-(methyl or phenyl)-
benzo[h]-1,2,4-triazino-[4ꢀ,3ꢀ:1,2]pyrimido[4,5-b]quinolin-8-
one (20a,b)
General Procedure
A mixture of compound 4b (3.89 g, 10 mmol) with chloroacetone or
phenacylbromide (10 mmol) was heated under reflux 5 h in 30 mL of dry
xylene. The solid precipitated that separated upon cooling was filtered
off and crystallized from an appropriate solvent to produce 20a,b in
high yields.

1882
A. B. A. Elgazzar et al.
7-(4-Chlorophenyl)-5,6-dihydro-9H-11-methyl-benzo[h]-1,2,4-
triazino[4ꢀ,3ꢀ:1,2]pyrimido[4,5-b]quinolin-8-one (20a)
Compound 4b (3.89 g, 10 mmol) and chloroacetone (0.93 g, 10 mmol).
The compound was obtained as pale white crystals and crystallized from
benzene (67%), m.p. 377–379◦C; IR (KBr) cm−1: 3420 (brs, NH), 2950
1
(CH alkyl), 1687 (CO), 1600 (C N), 1543 (C C); H NMR (DMSO-d6)
ppm: δ 2.05 (s, 3H, CH3), 2.50–2.55 (m, 2H, CH2), 2.70–2.85 (m, 2H,
CH2), 4.80 (s, 2H, CH2), 7.20–7.30 (d, 2H, phenyl), 7.35–7.40 (m, 1H,
phenyl), 7.45–7.55 (m, 4H, 2H phenyl + 2H phenyl), 8.25–8.40 (m, 1H,
phenyl) and 11.05 (brs, NH, D2O exchangable). Its MS, [M+], m/z 427
(100%). Analysis: C24H18ClN5O (427.8). Requires: C, 67.37; H, 4.24; N,
16.37. Found: C, 67.33; H, 4.27; N, 16.29.
7-(4-Chlorophenyl)-5,6-dihydro-9H-11-phenyl-benzo[h]-1,2,4-
triazino[4ꢀ,3ꢀ:1,2]pyrimido[4,5-b]quinolin-8-one (20b)
Compound 4b (3.89 g, 10 mmol) and phenacylbromide (1.99 g, 10 mmol).
The compound was obtained as a yellow powder and crystallized from
dimethylformamide (59%), m.p. 334–337◦C; IR (KBr) cm−1: 3279 (brs,
NH), 3039 (CH aryl), 2916 (CH alkyl), 1686 (CO), 1647 (C N), 1600
(C C), 1H NMR (DMSO-d6+TFA (1:1)) ppm: δ 2.55–2.60 (m, 2H, CH2),
2.80–2.90 (m, 2H, CH2), 5.45 (s, 2H, CH2 for triazine), 7.20–7.25 (d, 2H,
phenyl), 7.35–7.40 (m, 1H, phenyl), 7.45–7.65 (m, 7H, 2H phenyl + 5H
phenyl), 7.95–8.05 (m, 1H, phenyl) and 9.05 (brs, NH). Its MS, [M+],
m/z 489 (100%). Analysis: C29H20ClN5O (489.9). Requires: C, 71.09; H,
4.11; N, 14.29. Found: C, 71.12; H, 4.07; N, 14.23.
CONCLUSION
The prepared new ring systems seem to be interesting for biological
activity studies. Furthermore, the present investigation offers rapid
and effective new procedures for the synthesis of the polycondensed
new heterocyclic ring systems.
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Chem Abstr, 72, 31837u (1970).
[3] M. Shimizu, Y. Takase, S. Nakamura, H. Katae, A. Minami, K. Nakata, S. Inoue, M.
Ishiyama, and Y. Kubo, Antimicrob. Agents and Chemotherapy, 8, 132–138 (1975).
[4] P. B. Tolukdar, S. K. Sengupta, and K. A. Dotta, Indian J. Chem., 20B, 538 (1981);
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Polynuclear Heterocyclic Derivatives
1883
[5] R. E. Weishaar, M. C. Cain, and J. A. Bristol, J. mednl. Chem., 28, 537 (1985).
[6] G. Matolcsy, World Rev. Pest. Contr., 10, 50 (1971).
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