A new approach for fluorescent tetrahydrobenzo[f]pyrimido[4,5-b]quinolines and indeno fused pyrido[2,3-b]pyrimidines

Article abstract of DOI:10.1016/j.dyepig.2017.07.041

An unexpected discovery of one-pot domino reaction catalyzed by SnCl₂ for the construction of tetrahydrobenzo[f]pyrimido[4,5-b]quinolines and indeno fused pyrido[2,3-b]pyrimidines was exploited using 6-amino-1,3-dimethyluracil, substituted alde

Full text of DOI:10.1016/j.dyepig.2017.07.041

Accepted Manuscript
A new approach for fluorescent tetrahydrobenzo[f]pyrimido[4,5-b]quinolines and
indeno fused pyrido[2,3-b]pyrimidines
Saravanakumar Manickam, Sathiyanarayanan Kulathu Iyer
PII:
S0143-7208(17)30890-2
10.1016/j.dyepig.2017.07.041
DYPI 6130
DOI:
Reference:
To appear in: Dyes and Pigments
Received Date: 20 April 2017
Revised Date: 26 June 2017
Accepted Date: 17 July 2017
Please cite this article as: Manickam S, Kulathu Iyer S, A new approach for fluorescent
tetrahydrobenzo[f]pyrimido[4,5-b]quinolines and indeno fused pyrido[2,3-b]pyrimidines, Dyes and
Pigments (2017), doi: 10.1016/j.dyepig.2017.07.041.
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ACCEPTED MANUSCRIPT
A new approach for fluorescent tetrahydrobenzo[f]pyrimido[4,5-
b]quinolines and indeno fused pyrido[2,3-b]pyrimidines
Saravanakumar Manickam, Sathiyanarayanan Kulathu Iyer*
*Chemistry Department, School of Advanced Sciences, Vellore Institute of Technology
University, Vellore-632014, India. E-mail: sathiya_kuna@hotmail.com
Graphical abstract
Keywords: Pyrimido[4,5-b]quinoline, Pyrido[2,3-b]pyrimidine, Multi-component reaction,
Fluorescence, Domino reaction.

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Abstract
An unexpected discovery of one-pot domino reaction catalyzed by SnCl2 for the construction
of tetrahydrobenzo[f]pyrimido[4,5-b]quinolines and indeno fused pyrido[2,3-b]pyrimidines
was exploited using 6-amino-1,3-dimethyluracil, substituted aldehydes and ketones. The
optimized conditions were established after examining various reaction parameters such as
catalyst, solvent and additives. The current protocol is the best for performing the reaction
smoothly to achieve moderate to good yields and it exhibits many advantages including one-
pot manner, simple condensation, use of inexpensive catalyst and broad substrate scope. The
synthesis is much compatible with various functionalities and these compounds exhibited
fluorescence in solution and in the solid state.
Introduction
Fused nitrogen-containing heteroaromatic species exhibit rich biological activities and are used
as chemosensors in biomedical field [1]. Specifically pyrazoline [2], phenanthridine [3],
pyrazolopyridine [4], pyrimidopyridine [5] and xanthine [6] derivatives are pharmaceutically
important classes and they are found to occur in many effective antimicrobial [7], antiviral [8],
anti-inflammatory[9] and anticancer pharmacophores [10]. It is well known that the
synthesized unit with quinoline moiety plays an important role in medicinal chemistry [11], is
used in pharmaceutical agents and as a component in bioactive drugs such as luotonine-A,
quinine and chloroquinine [12]. Similarly and more importantly, compounds containing
pyrimido[4,5-b]quinoline and pyrido[2,3-b]pyrimidine segments exhibit various biological and
pharmaceutical activities, which reveal their versatility in drug discovery [13]. In addition,
benzo and indeno fused compounds with pyrimido[4,5-b]quinoline and pyrido[2,3-
b]pyrimidine have also been found to display interesting luminescent properties [14].

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Consequently, they are used in fluorescence sensors and they find application in
optoelectronics in areas like solar cells [15] and OLEDs [16].
Since the last few decades, Lewis acid catalyzed multi-component reactions (MCRs) [17] have
been gaining much attention because of their higher atom efficiency [18], avoidance of multi-
step process and improved yield [19]. Additional advantages of these MCRs including non-
toxic, non- hazardous, non-flammable and lowering of the side products increase its
importance in medicinal chemistry and synthetic organic chemistry [20]. In this way, tandem
reactions occur in one-pot process in which three or more reactants come together in a single
reaction vessel to form the desired product via intermediate transformations [21]. So far one-
pot synthesis has been achieved by employing InCl3 [22], CuI [23], ZnCl2 [24], GdCl3 [25],
molecular I2 [26], CAN [27], ZrOCl2.8H2O [28], lactic acid [29], BF3-OEt2 [30], FeCl3 [31] and
Bi(NO3)3.5H2O [32] as efficient catalysts. Efficacies in new approaches for the preparation of
biologically active molecules are of great significance with simple mechanism and good
selectivity. In continuation of this, herein we report the one-pot synthesis of
tetrahydrobenzo[f]pyrimido[4,5-b]quinolines and indeno-pyrido[2,3-b]pyrimidines using 15
mol% of SnCl2 as a catalyst via three-component domino reaction.
Previous literature reveals that, there have been no reports on the synthesis of 8, 10-dimethyl-
12-phenyl-5,6,10,12-tetrahydrobenzo[f]pyrimido[4,5-b]quinoline-9,11(7H,8H)diones (4) and
1,3-dimethyl-5-phenyl-1H-indeno[1’,2’:5,6]pyrido[2,3-b]pyrimidine-2,4(3H, 10H)-diones (5)
through the condensation of ketones (3a-b) with aldehyde (2a-j) and 6-amino-1,3-
dimethyluracil (1) [33]. However, to our knowledge we found only a few reports available on
synthesis of pyrimido[4,5-b]quinolines and indeno fused pyrido[2,3-d]pyrimidines in one-pot
via three-component coupling of 6-amino-1,3-dimethyluracil, aldehydes with cyclic-1,3-

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diketones. The reaction of 2-tetralone with 6-amino-1,3-dimethyluracil leads to formation of an
unexpected benzo[f]pyrimido[4,5-b]quinoline. Surprisingly, in the case of 2-indanone a
complete oxidation has occurred resulting in indeno[1’,2’:5,6]pyrido[2,3-b]pyrimidine. In the
present communication, we describe the synthesis and photophysical properties of
benzo[f]pyrimido[4,5-b]quinolines (BPQs) and indeno-pyrido[2,3-d]pyrimidines (IPPs).
Results and discussion:
We first set out experiments to investigate the role of catalyst for the formation of desired
products 4 and 5 (Scheme-1 and 2). For instance, an equimolar ratio of benzaldehyde, cyclic
ketone (3a-b) and amine (1), treated with 15 mol % of catalyst in ethanol under reflux
conditions afforded the desired product as given in Table 1 [34]. It was found that among the
chosen catalysts only I2, CAN, PTSA and SnCl2 allowed the reaction to progress smoothly
towards the desired product although the reaction was initiated by other catalysts like FeCl3,
NiCl2 and ZnCl2, the yield was less. We identified good results using 15 mol % SnCl2 as
catalyst affording compounds 4a, 5a with 66%, and 58% yields respectively within 16 h with
the formation of undesired aldol product as minor product. As a consequence, we increased the
loading of SnCl2 catalyst up to 30 mol% in order to lower the formation of side product but
ended up with the same results.
Table 1. Optimization of reaction conditions for the synthesis of benzo[f]pyrimido[4,5-
b]quinoline (4a) and indeno-pyrido[2,3-d]pyrimidine (5a).
Next we employed various acids and bases as additives to improve the yields. A higher yield
for 4a and 5a (81 and 84 %) was obtained when the catalyst system composed of SnCl2 and
AcOH was employed (Table 1, entry 20) and almost similar results were obtained with SnCl2

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and TFA system (Table 1, entry 19) in ethanol. Likewise, switching to HCl as an additive
gave product 4a-5a is low yields of 58-62% (Table 1, entries 14). We also performed the
low/moderate reaction employing various bases as additives such as piperidine, TEA, Na2CO3
and K2CO3 but the product yield diminished (Table 1, entries 15-18). To identify a suitable
solvent for reaction conditions, the reaction was carried out in various solvents. Ethanol and
isopropanol were considered to be the best choices for the synthesis of BPQ and IPP dyes
(Table 1, entry 21). Even though the reaction proceeded in DMF, the yield and the rate of the
reactions was lesser when compared to that of other solvents. However, there was no formation
of desired product in water. Moreover, the reaction in ethanol significantly enhanced the yield
of the desired product with less time and it also promoted the reaction rates.
Scheme 1. Scope of the reaction for synthesis of benzo[f]pyrimido[4,5-b]quinolines
derivatives
Scheme 2. Synthesis of indeno-pyrido[2,3-d]pyrimidines derivatives
With the optimal conditions in hand, we set our goals to explore the scope and generality of
this process and the results are summarized in Scheme 1. A variety of substituted
benzaldehydes (2a-j), amine (1) and different ketones underwent reaction smoothly in the
presence of SnCl2 to form the desired product 4 and 5. Generally, the three-component reaction
of 2-tetralone with aromatic aldehydes and amine (1) proceeded smoothly and the
corresponding products were obtained in moderate to good yields (30–85%). A variety of
functional groups such as dimethylamino, methoxy, ethoxy, isopropyl, cyano and halogen
groups substituted at the aromatic ring of the aldehyde were tolerated. The presence of
substituents at ortho position of aldehydes such as 4h, 4i and 4j allowed the reaction to

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continue moderately and yields of 35, 30 and 40 % respectively were obtained. Interestingly, in
cases of 2-indanone the reaction of aldehyde and amine proceeded smoothly and as a result
completely oxidized product was obtained in moderate to good yields (31–89%) as given in
Scheme 2. In the case of both ketones (2-tetralone and 2-indanone), 2-substituted aldehydes
such as 5h, 5i and 5j allowed the reaction to take place slowly with yields of 39, 31 and 42 %
respectively. This might be due to steric effect caused by substitution at the 2nd position.
Fig. 1. ORTEP diagram of compound 4g (CCDC= 1525833) (Top). Packing arrangement of
molecule in unit cell (bottom)
1
13
The synthesized structures were completely characterized by FTIR, H, C NMR and HRMS
analysis. A Single crystal of 4g was grown by dissolving the compound at room temperature
followed by slow evaporation of ethanol and tetrahydrofuran mixture and the ORTEP crystal
structure of compound 4g, is given in Fig. 1. A Single crystal of 4g was crystallized in
monoclinic pattern with space group of 2/c and 10 molecules were arranged in packing unit
cell. The phenyl ring at C5 appeared perpendicular to benzo[f]pyrimido[4,5-b]quinolines plane.
Significant intermolecular N-H….O interactions were found to exist along the crystallographic
axis direction with intermolecular distance of N-H….O (2.136 Å) (See supporting
information Figure S1). These intermolecular interactions linked the neighboring molecules,
which resulted in the formation of layer structures.
Table 2. Substrate scope with ketones and active methylene compounds
In order to investigate the substrate scope of this reaction with cyclic ketones we treated
benzaldehyde (2a) and amine (1) with various cyclic ketones, cyclohexanone (3c),
cyclopentanone (3d), acetophenone (3e), 1-tetralone (3f) and n-benzyl-4-piperdinone (3g).
Among the chosen ketones, the ketones (3c-3g) did not undergo conversion to their

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corresponding products under these optimized conditions and ended up with possible
Knoevenagel condensation products (Table 2, entry 1-5). Next we moved from cyclic ketones
to active methylene compounds such as ethyl acetoacetate, acetyl acetone, 8-hydroxy
naphthoquinone, malononitrile and diketone. However, the yields were less in case of 1,3-
cyclohexadione (3h), ethyl acetoacetate (3i) and acetylacetone (3j) in ethanol at 60 0C for 24 h
and they provided the desired compounds with the poor yields of 7 (22%). With 2-napthol
(3m) under the similar conditions no formation of desired product was observed. This clearly
suggests that the use of SnCl2 catalyst system suits only for 3a, 3b and 3h-j diketone
substrates. Using SnCl2 catalyst for 3c-m substrates did not give the desired products in the
given reaction conditions.
A tentative mechanism for this domino cyclization is outlined in Scheme 4. Firstly, the mono
benzylidine product I may be generated through SnCl2 catalyzed Knoevenagel condensation
between the aldehyde (2) and ketone (3a). Then, I which acts as Michael acceptor selectively
attacks C-5 position of 6-amino-1,3-dimethyl uracil and produce intermediate II which upon
hydrogen loss followed by dehydration would lead to generate target molecule (4). In the case
of formation of 5, the Knoevenagel products I (Michael acceptor) reacts with amino uracil (1)
followed by dehydration to form adduct II. The open chain intermediate (II) undergoes a
nucleophilic attack of Michael acceptor (I) to give intermediate III which upon loss of
hydrogen followed by oxidative cyclization forms corresponding product 5.
Scheme 3. Plausible mechanism for the formation of 4 and 5.

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Photophysical Properties
The absorption and emission measurements of 4a-j and 5a-j were recorded in acetonitrile
solvent and the representative data are summarized in Table 2. The absorption spectra of all
the compounds exhibited the absorption between 200-400 nm with the red shifted peak at 355
nm for 4d. All the derivatives exhibited similar absorbance profile with the lower energy band
at 340-350 nm assigned due to n-π* transitions and higher energy band at 260-290 nm due to
π-π* transitions (Fig. 2 left). For fewer derivatives, vibrational peaks were also observed below
250 nm. In general, increased molar absorption coefficient values (ε) were obtained for indeno
fused derivatives. For instance 4a showed absorbance maxima at 267, 346 nm with ε of
0.71X104 M-1cm-1 and 0.52104 M-1cm-1where as 5a exhibited absorbance maxima at 208, 348
nm with ε of 1.7X104 M-1cm-1 and 0.66X104 M-1cm-1.
All the dyes exhibited less intensified blue emission in solution and the emission spread in the
range of 381-430 nm as given in (Fig. 2 right) Dye 4a showed the emission maximum at 413
nm with the Stokes shift value of 4688 cm-1 whereas dye 5a exhibited blue shifted emission
maximum at 394 nm (∆ss=3355 cm-1). Moreover red shifted emission at 430 nm was observed
for compound 4d with electron withdrawing CN group along with a highest Stokes shift value
of 4914 cm-1 among the library. Dye 5h with -MeO substitution at ortho position had the
lowest Stokes shift value of 4914 cm-1 and displayed more blue shifted emission maximum at
381 nm. In general, indeno fused derivatives 5a-5j showed blue shifted emission with
decreased Stokes shift values compared to tetrahydrobenzo fused derivatives 4a-4j.
Photoluminescence quantum yields of the compounds (4a-j) were measured in CH3CN solvent
by using anthracene 340 as standard (ϕF = 0.27 in ethanol). From the table, it is clear that, very
low ϕF of the dyes suggest that emission is very weak in solution state. Measurements of solid

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state luminescence spectra of selected compounds revealed that the emission spectrum of 4a
was red shifted by 41 nm compared to its solution state and the same trend was observed for
the measured compounds. (Entry 4a-4d and 4f, Table 3). Further, to study the excited state
properties, fluorescence lifetime of 4a-j and 5a-j was measured in acetonitrile by exciting at
320 nm using time-correlated single-photon-counting technique and the corresponding data are
given in Figure 4. The lifetime maximum for 4h and 5a was measured to be 6.59 and 5.31 ns
respectively in acetonitrile solvent indicating six to three folds increase in respective series
when compared with the lowest (Table 3).
Table 3. Optical properties of 4a-j and 5a-j in CH3CN solvents.
Fig. 2. Absorptions (left) and fluorescence (right) spectra of 4a-j (top) and 5a-j (bottom)
recorded in Acetonitrile. Excitation wavelength is 320 nm.
Fig. 3. Solid state emission spectra of selected compounds 4a-d and 4f.
Figure 4. Photoluminescence Lifetime decay profile of 4a-j (left) and 5a-j (right)
Solvent Effect. The solvatochromic effects on the absorption and emission spectra for 4a-f and
5a-f in different solvents were measured and the data are summarized in Table 4, 5 and Figure
5, 6 and SI Figure S3 and relevant data are listed in supporting information. Unsubstituted and
donor-acceptor substituted derivatives (4b-c, 4f, 5a-c and 5f) in different solvents did not show
any solvatochromic behavior (see supporting information). On the other hand, the emission
properties of strong acceptor (-CN) derivatives 4d and 5d, the λ
values changed
max
dramatically by changing the solvent polarity. Fig. 4 and 5 show the λ max values of compound
4a displayed the smallest solvatochromic effects, whereas the largest solvatochromic effect
was observed for compound 4d and 5d. The charge transfer (CT) character in excited states of
4d and 5d are strong, whereas CT character of 4a is weaker. This is because of the strong

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interaction between acceptor (-CN) substitutent on the phenyl ring with the central pyridine at
the excited state. As far as the emission maxima was concerned, while moving from n-hexane
to acetonitrile solvent a red-shift of 71 and 101nm for dye 4a and 4d is observed. Similarly,
compound 5d exhibited large bathochromic shift of 111 nm. This longer emission result
reveals that the dipole moment of the excited state is higher than the ground state. The
difference in Stokes shift for 4d and 5d between non-polar to polar solvents can be considered
as charge transfer in the excited state. In non-polar solvents such as toluene and n-hexane, the
spectra of 4a and 5d showed vibrational transitions peak at 327-411 and 369-388 nm (4a and
5d) which were assigned to the locally excited state and intramolecular charge transfer (ICT)
transitions respectively. As the solvent polarity increases, the quantum yield values (ϕfl) (4a,
4d and 5d) increase along with the shapes of emission spectra resulting in broadened red-shift
emission. These results suggest that compounds 4a, 4d and 5d show solvatochromism through
ICT in the excited state.
Table 4. UV-Visible Absorption and Fluorescence Properties of 4a-f in various solvents.
Table 5. UV-Visible Absorption and Fluorescence Properties of 5a-f in various solvents.
Figure 5. Normalized fluorescence spectra of 4a and 4d in various solvents (2X10-5 M).
Figure 6. Normalized fluorescence spectra of 5d in various solvents (2X10-5 M).
Electrochemical Studies
Cyclic voltammograms were recorded to study electrochemical activity and to determine the
oxidation and reduction potential values of these systems. The electrochemical properties of
the compound 4a-f and 5a-f derivatives recorded in acetonitrile with 100 mM
tetrabutylammonium hexafluoro phosphate as supporting electrolyte and ferrocence as the
internal standard (E1/2 ferrocene= 0.67) at 50 mV/s scan rate, in order to estimate the energy

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gap (Eg) of these derivatives [35].The corresponding cyclic voltammograms are shown in Fig 7
and the reduction and oxidation peak are recorded in Table 4. There are many variations in the
oxidation and reduction potential values for 4a-f and 5a-f. However, the reduction and
oxidation potentials for all the compounds are much affected by substituents as indicated both
the strong donor (4c and 5c) and strong acceptor (4d and 5d) brings down the oxidation
potential values to much greater than the weaker donor (4b and 5b) and weaker acceptor (4f
and 5f). By comparing, the experimental band gap of 4a-f and 5a-f, it has been found to be the
smallest for the strong donor and strong acceptor than the non-substituted compounds (4a and
5a).
Table 4. Electrochemical Data of 4a-f and 5a-f in Acetonitrile solution with 100 mM TBAFP6
at a scan Rate of 50 mVs
Figure 7. Cyclic Voltammograms of 4a-f (right) and 5a-f (left) derivatives recorded in
acetonitrile; Pt working electrode, Ag/AgCl reference electrode, and Pt counter electrode.
Conclusions
We have described a simple multi-component procedure for the facile synthesis of 8, 10-
dimethyl-12-phenyl-5,6,10,12-tetrahydrobenzo[f]pyrimido[4,5-b]quinoline-9,11(7H,
8H)-
diones and indeno-fused 1,3-dimethyl-5-phenyl-1H-indeno[1’,2’:5,6]pyrido[2,3-b]pyrimidine-
2,4(3H,10H)-diones. The one-pot synthesis was made through the coupling of ketone, 6-
amino-1,3-dimethyluracil and substituted aldehydes (2) in ethanol solvent promoted by SnCl2
in an environmentally benign process with high yields and simple purification process.
Various reaction parameters such as catalyst, solvent and additives were screened to optimize
the reaction conditions and the current protocol was observed to be the best for performing the

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reaction smoothly. The synthesis was tolerated with various functionalities such as CN, Cl, F,
NMe2, MeO, EtO, Me and isopropyl. All the compounds displayed weak blue fluorescence in
solution state with large Stokes shift values and high molar extinction coefficient values.
Additionally, an increased emisssion was observed in solid state. The Luminescence spectra of
4a, 4d and 5d in non-polar to polar solvents showed broad bathochromic emission. The cyclic
voltammetry behavior of dyes 4a-f and 5a-f revealed the existence of both reversible oxidation
and reduction potential, indicating that both anions and cations are stable.
Experimental Section:
General Information: All commercial chemicals and solvents were purchased from Sigma
Aldrich, Sd-Fine and Alfa Aesar and used as received without further purification. NMR
spectra were taken on Bruker 400 MHz spectrometer using CDCl3 as the solvent. Chemical
shifts were referred to TMS (1H and 13C NMR) as an internal standard. UV-VIS and
fluorescence spectra were recorded on quartz cell. UV-vis spectra were taken using Shimadzu
UV-1800 spectrophotometer. Fluorescence spectra in solution and solid states were measured
using CARY-Eclipse fluorescence spectrophotometer in various solvents. Quantum yields
were determined using Anthracence and 2-Aminopyridine as standard (ϕF = 0.27 in ethanol and
ϕF = 0.60 in 0.1M conc. H2SO4). HRMS values were obtained on Joel GC Mate II GC- Mass
Spectrometer. FTIR spectra of the synthesized organic compounds were recorded using a
JASCO-4100 spectrometer instrument. Electrochemical measurements were made using a CH
instrument (CH 600E) electrochemical analyser. A conventional three-electrode configuration,
consisting of a glassy carbon working electrode, Pt-wire counter electrode, and Ag/AgCl
reference electrode, was used. 0.1 M tetrabutylammoniumhexa fluoro phosphate (TBAFP6)
was used as supporting electrolyte. The fluorescence lifetime measurements were carried out

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using a single photon counting method. The fluorescence decay curves were measured by
exciting the molecule at 320 nm, in <200 ps light using Nano LED.
General procedure for the synthesis of compounds (4 and 5). 1.0 equivalent of acetic acid
and 15 mol% of SnCl2 was added to the round-bottomed flask and then equimolar ratio of 6-
amino 1,3-dimethyluracil (1), substituted benzaldehyde (2a-j) and cyclic ketone (3a-b) were
successively added followed by reflux for appropriate time as given in scheme 1 and 2. The
course of the reaction was monitored by TLC analysis and after completion the mixture was
cooled to room temperature. The crude was purified by silica gel chromatography using
hexane/ethyl acetate (9:1) as the elutant and gave moderate yields.
8,10-dimethyl-12-phenyl-5,7,8,12-tetrahydrobenzo[f]pyrimido[4,5-b]quinoline-9,11(6H,
10H)-dione (4a)
0
White solid; Melting point: 248-250 C; IR (KBr): 3302, 3055, 3026, 2941, 2883, 2823,
1683, 1666, 1579, 1602, 1512, 1489, 1471, 1345 , 1427, 1329, 1246, 1226, 1138, 1080, 1047,
910 , 829, 754, 740 cm-1;1 H NMR (400 MHz, DMSO):
δ ppm: 2.60-2.51 (m, 1H, CH2), 2.87-
2.75 (m, 3H, CH2), 3.12 (ss, 3H, CH3), 3.44 (ss, 3H, CH3), 5.12 (ss, 1H, chiral proton), 6.99-
6.95 (t, J = 8 Hz, 1H, Ar-CH), 7.08-7.06 (m, 3H, Ar-CH), 7.21-7.17(t, J = 8 Hz, 3H, Ar-
CH), 7.42-7.40 (d, J =8 Hz, 2H, Ar-CH), 8.62 (ss, 1H, NH);13C NMR (100 MHz, DMSO):
δ
ppm: 24.7, 27.5, 29.8, 38.9, 39.1, 39.3, 40.1, 88.1, 108.8 ,121.3, 1247, 127.9, 133.0, 133.7,
133.8, 144.0, 146.1, 150.5, 160.8. HRMS (ESI/TOF-Q): m/z M+ Calculated for C23H21N3O2
371.1634; Found.371.1630.
12-(4-methoxyphenyl)-8,10-dimethyl-12-phenyl-5,7,8,12-tetrahydrobenzo[f]pyrimido[4,5-
b]quinoline-9,11(6H, 10H)-dione (4b)

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0
Yellow solid; melting point: 251-253 C; IR (KBr): 3257 , 3219, 2937, 2829, 1685, 1664,
1606 , 1506, 1479, 1454, 1435, 1325, 1246, 1220, 1174, 1112, 1035 , 981, 752, 831, 935, 609
cm-1;1 H NMR (400 MHz, CDCl3):
δ ppm: 2.66-2.54 (m, 2H, CH2), 2.97-2.95 (t, J= 4 Hz,
2H, CH2), 3.33 (ss, 3H, CH3), 3.50 (ss, 3H, OCH3), 3.72 (ss, 3H, CH3), 5.28 (ss, 1H, chiral
proton), 5.93 (ss, 1H, NH), 6.79-6.76 (d, J=12 Hz, 2H, Ar-CH), 7.05 -7.03 (t, J= 8 Hz, 1H,
Ar-CH), 7.12 -7.10 (t, J= 8 Hz, 2H, Ar-CH), 7.29 -7.27 (d, J=8 Hz, 1H, Ar-CH), 7.44-
7.42 (d, J= 8 Hz, 2H, Ar-CH);13C NMR (100 MHz, CDCl3):
δ ppm: 26.9, 28.1,28.5,
36.2,55.1, 76.7, 77.0, 77.3, 90.4, 111.1, 113.7, 122.5, 125.6, 126.8, 127.2,
128.8, 130.3, 133.3, 133.5, 137.4, 143.0, 151.0, 158.1, 161.0. HRMS (ESI/TOF-
Q): m/z M+ Calculated for C24H23N3O3 401.1739; Found.401.1736.
12-(4-dimethylaminophenyl)-8,10-dimethyl-12-phenyl-5,7,8,12-tetrahydrobenzo[f]
pyrimido[4,5-b]quinoline-9,11(6H, 10H)-dione (4c)
Green solid; melting point: 239-241 0C; IR (KBr): 3296, 3271, 2800, 2335, 1668, 1695, 1602,
1512, 1469, 1442, 1357, 1328, 1253, 1224, 1201,1157, 1124 ,1049, 995, 947, 927, 812 cm-1;
1H NMR (400 MHz, CDCl3):
δ ppm: 2.68-2.55 (m, 2H, CH2), 2.70 (ss, 6H, N(CH3)2), 2.99-
2.97 (t, J= 8 Hz, 2H, CH2), 3.33 (ss, 3H, CH3), 3.46 (ss, 3H, CH3), 5.24 (ss, 1H, chiral proton),
5.96 (ss, 1H, NH), 6.63-6.61 (d, J=8 Hz, 2H, Ar-CH), 7.04-7.00 (m, 1H, Ar-CH), 7.12-7.07 (m,
2H, Ar-CH), 7.31-7.30 (t, J=4 Hz, 1H, Ar-CH), 7.38-7.36 (d, J=8 Hz, 2H, Ar-CH);13C NMR
(100 MHz, CDCl3):
δ ppm: 26.9, 28.1, 28.2, 28.5, 35.9, 40.6, 76.7, 77.3, 90.7, 111.2, 112.5,
122.6, 125.5, 126.8, 127.1, 128.5, 130.2, 133.4, 133.5, 142.9, 149.2, 151.0, 161.8. HRMS
(ESI/TOF-Q): m/z M+ Calculated for C25H26N4O2 414.2056; Found.414.2051.
4-(8,10-dimethyl-9,11-dioxo1-5,67,8,9,10,11,12-octahydrobenzo[f]pyrimido[4,5-
b]quinolin-12-yl)benzonitrile (4d)

ACCEPTED MANUSCRIPT
Green solid; melting point: 280-282 0C; IR (KBr): 3325, 3007, 2831, 2235, 1693, 1672, 1637,
-
1506, 1600, 1485, 1471, 1436, 1327, 1253, 1220, 1114,
1049 ,746 ,732, 578 , 559 ,435.91 cm
1;1 H NMR (400 MHz, DMSO):
1H, CH ), 2.85-2.82 ( 3H, CH ),
δ ppm: 2.59-2.51 (m, m,
2
2
3.10 (ss, 3H, CH3), 3.43 (ss, 3H, CH3), 5.22 (ss, 1H, chiral proton), 7.00-6.98 (t, J= 8 Hz, 1H,
Ar-CH), 7.09-7.07 (q, J=8 Hz, 2H, Ar-CH), 7.18-7.16 (d, J= 8 Hz, 1H, Ar-CH), 7.61-7.59 (d,
J= 8 Hz, 2H, Ar-CH), 7.68-7.66 (d, J= 8 Hz, 2H, Ar-CH), 8.68 (ss, 1H, NH);13C NMR (100
MHz, DMSO)
δ ppm: 24.7, 27.2, 27.5, 36.9, 38.9, 39.1, 39.3, 39.5, 7.39.9, 40.1, 87.1, 107.9,
108.8, 118.8, 121.2, 125.1, 126.4, 127.1, 128.8, 131.9, 133.3, 133.6, 133.8, 144.3, 150.4, 151.4,
160.8. HRMS (ESI/TOF-Q): m/z M+ Calculated for C24H20N4O2 396.1586; Found.396.1582.
12-(4-ethoxyphenyl)-8,10-dimethyl-12-phenyl-5,7,8,12-tetrahydrobenzo[f]pyrimido[4,5-
b]quinoline-9,11(6H, 10H)-dione (4e)
0
Yellow solid; melting point: 196-198 C; IR (KBr):1697, 1663, 1602, 1506, 1471, 1438,
-1 1
1377, 1328, 1222, 1112, 997, 920, 653, 644, 570, 543, 522
. cm ; H NMR (400 MHz,
Hz, CH 2.60-2.58 (q, J= 8 Hz, 1H, CH ), 2.84-2.75
3H, 3),
DMSO):
δ
ppm: 1.28-1.26 (t, J= 8
2
(m, 3H, CH2), 2.86 (ss, 3H, CH3), 3.43 (ss, 3H, CH3), 3.93-3.92 (q, J= 4Hz, 2H, CH2), 5.06
(ss, 1H, chiral proton), 6.74-6.72 (d, J=8 Hz, 2H, Ar-CH), 6.99-6.97 (t, J= 8 Hz, 1H, Ar-CH),
7.09-7.07 (q, J= 8 Hz, 2H, Ar-CH), 7.19-7.17 (d, J= 8 Hz, 1H, Ar-CH), 7.29-7.27 (d, J= 8 Hz, 2H,
Ar-CH), 8.56 (ss, 1H, NH);13C NMR (100 MHz, DMSO):
δ ppm: 14.6 ,24.7, 27.5, 29.7,
35.6, 30.6, 30.8, 31.1, 39.2, 39.5, 39.9 ,40.1, 62.7, 88.4, 109.9, 113.7, 121.3, 124.8,
126.3, 127.0, 128.6, 132.7, 133.8, 138.1 ,143.7 ,150.5, 156.0, 160.8. HRMS (ESI/TOF-
Q): m/z M+ Calculated for C25H25N3O3 415.1896; Found.415.1893.
12-(4-fluorophenyl)-8,10-dimethyl-12-phenyl-5,7,8,12-tetrahydrobenzo[f]pyrimido[4,5-
b]quinoline-9,11(6H, 10H)-dione (4f)

ACCEPTED MANUSCRIPT
0
White solid; melting point: 260-262 C; IR (KBr):3327, 2941, 2823, 1689, 1666, 1606, 1514,
-
1504, 1475, 1450, 1431, 1423, 1328, 1247, 1219, 1153,
1138, 1047, 740, 723, 690, 582 cm
1;1H NMR (400 MHz, DMSO):
δ
ppm: 2.60-2.58 (q, J= 8
Hz CH 2.86-2.76 (m, 3H,
, 1H, 2),
CH2), 3.12 (ss, 3H, CH3), 3.13 (ss, 3H, CH3), 5.09 (ss, 1H, chiral proton), 7.01-6.96 (m, 2H
Ar-CH), 7.09-7.03 (m, 3H Ar-CH), 7.18-7.16 (d, J= 8 Hz, 1H, Ar-CH), 7.44-7.42 (t, J= 8
Hz, 2H, Ar-CH), 8.61 (ss, 1H, NH);13C NMR (100 MHz, D M S O ):
δ ppm: 24.7, 27.4,
27.5, 29.8, 35.8, 38.9, 39.1, 39.3, 39.5, 39.7, 39.9 ,40.1 ,87.9, 108.6, 114.4, 114.4, 114.6,
121.22, 124.9, 126.3, 127.1 ,129.4, 133.1, 133.5 ,133.8, 142.2 , 144.0, 150.5, 159.4 , 160.8,
161.8. HRMS (ESI/TOF-Q): m/z M+ Calculated for C23H20FN3O2 389.1540; Found.389.1520.
12-(4-isopropylphenyl)-8,10-dimethyl-12-phenyl-5,7,8,12-tetrahydrobenzo[f]
pyrimido[4,5-b]quinoline-9,11(6H, 10H)-dione (4g)
0
Yellow solid; melting point: 240-242 C; IR (KBr): 1699, 1600, 1514, 1400, 1440, 1328,
cm-1;1H NMR (400 MHz, DMSO):
δ ppm: 1.13-1.11
1253, 1222, 1047 ,993 , 827 ,725 ,692
(ss, 6H, CH3),
Hz,
CH 2.88-2.72 (m, 4H, CH and CH), 3 . 1 2 (ss,
1H, 2),
2.61-2.58 (q, J= 12
2
3H, CH3), 3 . 4 3 (ss, 3H, CH3), 5.10 (ss, 1H, chiral proton), 6.99-6.97 (t, J= 8 Hz, 1H, Ar-CH),
7 . 0 9 - 7 . 0 6 (t, J= 12 Hz, 4H, Ar-CH), 7.21-7.19 (d, J= 8 Hz, 1H, Ar-CH), 7.32-7.30 (d,
J= 8 Hz, 2H, Ar-CH), 8.60 (ss, 1H, NH);13C NMR (100 MHz, DMSO):
δ ppm: 23.8 ,23.9,
26.9, 28.1, 28.5, 33.5, 36.5, 76.7, 77.0, 77.3, 90.4, 111.1, 122.6, 125.6, 126.4, 126.0,
127.1, 127.7, 130.4, 133.4, 133.5, 142.4, 143.1, 146.8 ,151.0, 161.0. HRMS (ESI/TOF-Q):
m/z M+ Calculated for C26H27N3O2 413.2103; Found.413.2101.
12-(2-methoxyphenyl)-8,10-dimethyl-12-phenyl-5,7,8,12-tetrahydrobenzo[f]
pyrimido[4,5-b]quinoline-9,11(6H, 10H)-dione (4h)

ACCEPTED MANUSCRIPT
0
Yellow solid; melting point: 271-273 C; IR (KBr): 3368, 2941, 2835, 1687, 1664, 1612,
1514, 1487, 1469 , 1436 ,1328, 1247, 1224, 1184, 1089, 1049, 1028 ,927, 820, 748, 727
cm-1;1H NMR (400 MHz, DMSO):
(ss, 3H, CH ),
δ
ppm: 2.52-2.42 (m, 1H,
CH
2), 2.80-2.63 (m. 3H,
CH
2),
(ss, 3H, CH ), 3.88 (ss, 3H, OCH ), (ss, 1H, chiral proton),
5.46
3.08
3.47
3
3
3
6.81-6.79 (t, J= 8 Hz, 1H, Ar-CH), 6.87-6.85 (d, J= 8 Hz, 1H, Ar-CH), 6.97-6.95, (t, J= 8
Hz, 1H, Ar-CH), 7.10-7.00 (m, 3H, Ar-CH), 7.29-7.28 (d, J= 4 Hz, 1H, Ar-CH), 7.52-7.50, (d,
J= 8 Hz, 1H, Ar-CH), 8.50 (ss, 1H, NH);13C NMR (100 MHz, DMSO):
δ ppm: 24.9 ,27.4
,27.5, 29.8, 30.3, 38.9, 39.1, 39.3, 39.5, 39.7, 39.9, 40.1, 55.9, 88.5, 110.0, 111.5, 120.6,
121.2, 124.7, 126.1, 126.8, 127.1, 132.3, 133.7, 134.2, 135.9, 144.6, 150.1 , 156.1, 160.5.
HRMS (ESI/TOF-Q): m/z M+ Calculated for C24H23N3O3 401.1739; Found.401.1736.
12-(2-ethoxyphenyl)-8,10-dimethyl-12-phenyl-5,7,8,12-tetrahydrobenzo[f]pyrimido[4,5-
b]quinoline-9,11(6H, 10H)-dione (4i)
0
White solid; melting point: 230-232 C; IR (KBr): 3221, 1695, 1606, 1514, 1473, 1436,
cm-1;1H NMR (400 MHz, DMSO):
1242, 1224, 1159, 1029, 894, 827, 744 , 648, 528, 491
Hz,
CH 2.60-2.58 (m, 1H, CH ), 2.88-2.73 (m, 3H, CH ),
δ
ppm: 1.27-1.25 (t, J= 8
3H,
3),
2
2
2.90 (ss, 3H, CH ), 3.36 (ss, 3H, CH ), 3.93-3.92 (q, J= 4 Hz, 2H, CH ),
(ss, 1H, chiral
5.05
3
3
2
proton), 6.74-6.72 (d, J= 8 Hz, 2H, Ar-CH), 6.99-6.97 (t, J= 8 Hz, 1H, Ar-CH), 7.09-7.07 (q, J= 8
Hz, 2H, Ar-CH), 7.19-7.17 (d, J= 8 Hz, 1H, Ar-CH), 7.29-7.24 (d, J= 8 Hz, 2H, Ar-CH), 8.52
(ss, 1H, NH);13C NMR (100 MHz, DMSO):
δ ppm: 14.9, 24.9, 27.4, 27.5, 29.8, 31.3,
38.8, 39.1, 39.3, 39.5, 39.7, 39.9, 40.1, 63.4, 88.24, 109.6, 111.8, 120.1, 121.3, 124.6,
126.0, 126.8, 127.0, 130.3, 132.3, 133.7, 134.3, 135.1, 144.6, 150.6, 155.6, 160.5.
HRMS (ESI/TOF-Q): m/z M+ Calculated for C25H25N3O3 415.1896; Found.415.1890.
12-(2-chlorophenyl)-8,10-dimethyl-12-phenyl-5,7,8,12-tetrahydrobenzo[f]pyrimido[4,5-

ACCEPTED MANUSCRIPT
b]quinoline-9,11(6H, 10H)-dione (4j)
0
Yellow solid; melting point: 258-260 C; IR (KBr): 3319, 1680, 1625, 1516, 1467, 1436,
-1 1
1359, 1253, 1222, 1134, 1045, 987, 829, 758, 742, 638, 547, 49
cm ; H NMR (400 MHz,
Hz, CH 2.72-2.57 (m, 3H, CH2), 2.99 (ss, 3H,
1H, 2),
DMSO):
δ
ppm: 2.46-2.43 (t, J= 12
CH ), 3.38 (ss, 3H, CH ),
(ss, 1H, chiral proton), 6.90-6.89 (t, J= 4 Hz, 1H, Ar-CH), 7.02-
5.41
3
3
7.00 (q, J= 8 Hz, 3H, Ar-CH), 7.14-7.12 (q, J= 8 Hz, 2H, Ar-CH), 7.43-7.41 (dd, J= 8 Hz, 2H,
Ar-CH), 8.55 (ss, 1H, NH);13C NMR (100 MHz, DMSO):
δ
ppm: 24.9, 27.4, 29.9, 34.6,
38.8, 39.0, 39.2, 39.4, 39.7, 39.9, 40.1, 87.9, 109.1, 121.1, 124.9, 126.7 ,127.0, 127.1,
127,6 ,128.9, 131.3, 131.8, 133.3, 133.8, 133.9, 144.0,144.5,150.5,160. HRMS
(ESI/TOF-Q): m/z M+ Calculated for C23H20ClN3O2 405.1244; Found.405.1242.
1,3-dimethyl-5-phenyl-1,10-dihydro-2H-indeno[1’,2’:5,6]pyrido[2,3-d]pyrimidine-
2,4(3H)-dione (5a)
Brown solid; Melting point: 188-190 0C; IR (KBr): 3726, 3626, 3055, 3016, 2918, 2835, 2335,
1741, 1595, 1562, 1502, 1431, 1352, 1300, 1236, 1182, 1136, 1028, 977, 906, 852, 829, 798,
761, 738. cm-1 ;1 H NMR (400 MHz, CDCl3)
δ ppm: 3.37 (ss, 3H, CH3), 3.85 (ss, 3H, CH3),
4.07 (s, 2H, CH2), 6.19-6.17 (t, J=8 Hz, 1H, Ar-CH), 7.04-7.02 (t, J= 8 Hz 1H, Ar-CH), 7.27-
7.22 (m, 3H, Ar-CH), 7.52-7.50 (d, J= 8 Hz, 1H, Ar-CH), 7.57 (s, 3H, Ar-CH);13C NMR (100
MHz, CDCl3)
δ ppm: 28.4, 30.3, 39.2, 76.7, 77.0, 77.3, 106.8, 123.1, 124.8, 126.5, 127.1,
127.4, 128.0, 128.9, 130.2, 137.9, 138.5, 140.5, 147.1, 150.7, 151.3, 161.1, 169.4. HRMS
(ESI/TOF-Q): m/z M+ Calculated for C22H17N3O2 355.1321; Found.355.1320.
5-(4-methoxyphenyl)-1,3-dimethyl-1,10-dihydro-2H-indeno[1’,2’:5,6]pyrido[2,3-
d]pyrimidine-2,4(3H)-dione (5b)

ACCEPTED MANUSCRIPT
0
White solid; melting point: 201-203 C; IR (KBr): 2927, 2831, 1735, 1600, 1560, 1508,
1433, 1382, 1352, 1246, 1234, 1029, 831, 802, 752, 669, 578, 507.cm-1;1 H NMR (400 MHz,
CDCl3):
δ ppm: 3.40 (ss, 3H, CH3), 3.87 (ss, 3H, CH3), 3.97 (ss, 3H, OCH3), 4.09 (s,
2H, CH2), 6.37-6.35 (d, J=8 Hz, 1H, Ar-CH), 7.11 -7.09 (t, J= 8 Hz, 1H, Ar-CH), 7.15 -
7.13 (d, J=8 Hz, 2H, Ar-CH), 7.23- 7.21 (d, J= 8 Hz, 2H, Ar-CH), 7.30-7.29 (t, J= 4 Hz, 1H,
Ar-CH), 7.55-7.53 (d, J= 8 Hz, 1H, Ar-CH);13C NMR (100 MHz, CDCl3):
δ ppm: 28.4, 30.3,
39.2, 55.2, 76.7, 77.0, 77.3, 107.1, 114.4, 123.2, 124.7, 127.1, 127.3, 127.8, 129.9, 130.7,
138.7, 140.4, 147.2, 150.7, 151.3, 159.3, 161.2, 169.3. HRMS (ESI/TOF-Q): m/z M+
Calculated for C27H21NO 385.1426; Found. HRMS (ESI/TOF-Q): m/z M+ Calculated for
C23H19N3O3 385.1426; Found.385.1422.
5-(4-(dimethyamino)phenyl)-1,3-dimethyl-1,10-dihydro-2H-indeno[1’,2’:5,6]pyrido[2,3-
d]pyrimidine-2,4(3H)-dione (5c)
Orange solid; melting point: 190-192 0C; IR (KBr): 2958, 1737, 1724, 1598, 1556, 1504, 1490,
1
1436, 1415, 1379, 1348, 1265, 1186, 1134, 1101, 831, 802, 759, 752, 740. cm1 ; H NMR
(400 MHz, CDCl3): δ ppm: 3.07 (ss, 6H, 2CH3), 3.38 (ss, 3H, CH3), 3.83 (ss, 3H, CH3),
4.05 (s, 2H, CH2), 6.49-6.47 (d, J=8 1H, Ar-CH), 6.92-6.91 (q, J= 4 Hz, 2H, Ar-CH), 7.13-
7.08 (m, 3H, Ar-CH), 7.26-7.22 (m, 1H, Ar-CH) 7.51-7.49 (d, J=8 Hz, 1H, Ar-CH);13C NMR
(100 MHz, CDCl3):
δ ppm: 28.5, 30.3, 39.2, 40.4, 76.7, 77.0, 77.3, 107.4, 112.4, 123.4, 124.6,
125.1, 127.1, 127.5, 131.0, 139.0, 140.4, 148.3, 150.0, 150.7, 151.4, 161.2, 169.1. HRMS
(ESI/TOF-Q): m/z M+ Calculated for C24H22N4O2 398.1743; Found.398.1740.
4-(1,3-dimethyl-2,4-dioxo2,3,4,10-tetrahydro-1H-indeno[1’,2’:5,6]pyrido[2,3-d]pyrimidin-
5-yl)benzonitrile (5d)

ACCEPTED MANUSCRIPT
0
Yellow solid; melting point: 280-282 C; IR (KBr): 3076, 2978, 2935, 2833, 1737, 1726,
1598, 1558, 1504, 1492, 1431, 1411, 1240, 1182, 1047, 736, 678. cm-1 ;1
H NMR (400 MHz,
CDCl
3):
(ss, 3H, CH ), 3.85 (ss, 3H, CH ), 4.10 (ss, 2H, CH ),
6.14-6.12
3 3 2
δ
ppm: 3 . 3 6
Hz, 1H, Ar-CH), 7.09-7.07 (t, J= 8 Hz, 1H, Ar-CH), 7.31-7.29 (t, J= 8 Hz, 1H, Ar-
(d, J=8
CH), 7.43-7.41 (d, J= 8 Hz, 2H, Ar-CH), 7.56-7.54 (d, J= 8 Hz, 1H, Ar-CH), 7.88-7.86 (d, J=
8 Hz, 2H, Ar-CH);13C NMR (100 MHz, CDCl3):
δ
ppm: 28.5, 30.3, 39.2, 76.7, 77.0, 77.3,
106.3, 112.1, 118.7, 122.6, 125.1, 127.3, 127.9, 129.5, 129.9, 132.7, 137.8, 140.6, 143.1,
144.4, 150.7, 151.1, 161.1, 170.0. HRMS (ESI/TOF-Q): m/z M+ Calculated for C23H16N4O2
380.1273; Found.380.1271.
5-(4-chlorophenyl)-1,3-dimethyl-1,10-dihydro-2H-indeno[1’,2’:5,6]pyridi[2,3-
d]pyrimidine-2,4(3H)-dione (5e)
0
Yellow solid; melting point: 196-198 C; IR (KBr): 2978, 1735, 1726, 1597, 1560, 1508,
1452, 1436, 1425, 1381, 1236, 1174, 1134, 1111, 1047, 833, 802, 756, 740, 709. cm1 ;1
H NMR
CDCl
3): δ ppm: 3.30
(ss, 3H, CH ), 3.78 (ss, 3H, CH ), 4.01 (ss, 2H, CH ),
3 3 2
(400 MHz,
6.22-6.20 (d, J= 8 Hz, 1H, Ar-CH), 7.03-7.01 (t, J= 8 Hz, 1H, Ar-CH), 7.22-7.14 (m, 4H,
Ar-CH), 7.50-7.45 (m, 3H, Ar-CH);13C NMR (100 MHz, CDCl3):
δ
ppm: 28.4, 30.3, 39.2,
76.7, 77.0, 77.3, 106.7, 123.0, 124.9, 127.3, 127.6, 128.2, 129.3, 130.1, 134.1, 136.3, 138.2,
140.5, 145.7, 150.7, 151.2, 161.1, 169.69. HRMS (ESI/TOF-Q): m/z M+ Calculated for
C22H16ClN3O2 389.0931; Found. 389.0930.
5-(4-fluorophenyl)-1,3-dimethyl-1,10-dihydro-2H-indeno[1’,2’:5,6]pyridi[2,3-
d]pyrimidine-2,4(3H)-dione (5f)
0
White solid; melting point: 220-222 C; IR (KBr): 2962, 2837, 2335, 1730, 1597, 1573, 1506,
1435, 1355, 1292, 1244, 1176, 1130, 1066, 1026, 906, 860, 750, 800, 719, 684. cm-1;1
HNMR

ACCEPTED MANUSCRIPT
CDCl
3): δ ppm: 3.36
(ss, 3H, CH ), 3.82 (ss, 3H, CH ), 4.06 (ss, 2H, CH ),
3 3 2
(400 MHz,
6.26-6.24 (d, J= 8 Hz, 1H, Ar-CH), 7.08-7.06 (t, J= 8 Hz, 1H, Ar-CH), 7.26-7.17 (m, 6H,
Ar-CH), 7.52-7.50 (d, J= 8 Hz, 1H, Ar-CH);13C NMR (100 MHz, CDCl3):
δ
ppm: 28.4,
30.3, 39.2, 76.7, 77.0, 77.3, 106.9, 115.8, 116.0, 116.2, 122.9, 123.4, 124.9, 127.2, 127.3,
127.5, 128.5, 128.5, 129.1, 130.4, 131.3, 131.4, 133.1, 133.7, 133.7, 138.4, 140.5, 146.0,
150.7, 151.2, 161.1, 163.8, 169.5. HRMS (ESI/TOF-Q): m/z M+ Calculated for C22H16FN3O2
373.1227; Found.373.1224.
5-(4-isopropylphenyl)-1,3-dimethyl-1,10-dihydro-2H-indeno[1’,2’:5,6]pyridi[2,3-
d]pyrimidine-2,4(3H)-dione (5g)
0
Yellow solid; melting point: 188-190 C; 3061, 2225, 1575, 1504, 1436, 1415, 1386, 1357,
1300, 1265, 1230, 1132, 1070, 833, 756, 721, 684, 648. cm-1; 1
H NMR (400 MHz, CDCl3):
δ
(ss, 3H, CH ), 3.84
ppm: 1.39-1.38 (ss, 6H, 2CH3), 3.07-3.05 (d, J= 8 Hz, 1H, CH), 3.37
3
(ss, 3H, CH3), 4.05 (ss, 2H, CH2), 6.11-6.09 (d, J=8 Hz, 1H, Ar-CH), 7.00-6.99 (t, J= 4
Hz, 1H, Ar-CH), 7.25-7.18 (m, 3H, Ar-CH), 7.50-7.42 (m, 3H, Ar-CH);13C NMR (100
MHz, CDCl3):
δ ppm: 24.0, 28.4, 30.3, 33.9, 39.2, 76.7, 77.0, 77.3, 106.9, 123.2, 124.7,
126.4, 127.0, 127.3, 135.3, 138.7, 140.4, 147.6, 148.6, 151.4, 161.2, 169.2. HRMS (ESI/TOF-
Q): m/z M+ Calculated for C25H23N3O2 397.179; Found.397.1750.
5-(2-methoxyphenyl)-1,3-dimethyl-1,10-dihydro-2H-indeno[1’,2’:5,6]pyridi[2,3-
d]pyrimidine-2,4(3H)-dione (5h)
0
Yellow solid; melting point: 202-204 C; IR (KBr): 3064, 2900, 2337, 1735, 1595, 1573,
1506, 1458, 1433, 1367, 1300, 1220, 1132, 1068, 1014, 904, 804, 756, 686, 646, 569. cm-1 ;1
H
CDCl
3): δ ppm: 3.37
(ss, 3H, CH ), 3.68 (ss, 3H, CH ), 3.85 (ss, 3H,
3 3
NMR (400 MHz,
OCH3), 4.07 (ss, 2H, CH2), 6.35-6.34 (d, J= 4 Hz, 1H, Ar-CH), 7.07-7.05 (t, J= 8 Hz, 1H,

ACCEPTED MANUSCRIPT
Ar-CH), 7.17-7.12 (m, 3H, Ar-CH), 7.26-7.24 (t, J= 8 Hz, 1H, Ar-CH), 7.55-7.53 (t, J= 8 Hz,
2H, Ar-CH);13C NMR (100 MHz, CDCl3):
δ ppm: 28.4, 30.2 39.2, 55.6, 55.8, 76.7, 77.0,
77.4, 107.5, 111.2, 121.3, 122.6, 124.7, 126.8, 127.2, 127.8, 129.7, 130.3, 138.9, 140.5, 144.3,
150.7, 151.4, 155.9, 158.0, 160.9, 169.4. HRMS (ESI/TOF-Q): m/z M+ Calculated for
C23H19N3O3 385.1426; Found.385.1420.
5-(2-ethoxyphenyl)-1,3-dimethyl-1,10-dihydro-2H-indeno[1’,2’:5,6]pyridi[2,3-
d]pyrimidine-2,4(3H)-dione (5i)
0
Yellow solid; melting point: 206-208 C; IR (KBr): 3057, 2980, 2926, 2337, 1710, 1573,
1506, 1384, 1300, 1240, 1174, 1112, 1043, 1010, 920, 802, 758, 715, 686, 646. cm-1 ;1
H NMR
CDCl
3):
Hz,
(ss, 3H, CH ),3.85 (ss,
3H, CH3), 3.38
3
(400 MHz,
δ
ppm: 1.04-1.02 (t, J= 8
3H, CH3), 4.02-3.90 (m, 2H, CH2), 4 . 0 7 (ss, 2H, CH2), 6.40-6.38 (d, J= 8 Hz, 1H, Ar-
CH), 7.15-7.03 (m, 4H, Ar-CH), 7.26-7.24 (t, J= 8 Hz, 1H, Ar-CH), 7.52-7.50 (d, J= 8 Hz, 2H,
Ar-CH);13C NMR (100 MHz, CDCl3):
δ ppm: 14.6, 28.4, 30.2, 39.2, 64.0, 76.7, 77.0, 77.3,
107.5, 112.4, 121.1, 122.8, 124.7,127.0, 127.1,. 127. 1, 127. 9,129. 6, 130.3, 138.9, 140.5,
144.6, 150.6, 151.5, 155.3, 160.9, 169.3. HRMS (ESI/TOF-Q): m/z M+ Calculated for
C24H21N3O3 399.1583; Found.399.1580.
5-(2-fluorophenyl)-1,3-dimethyl-1,10-dihydro-2H-indeno[1’,2’:5,6]pyridi[2,3-
d]pyrimidine-2,4(3H)-dione (5j)
0
Yellow solid; melting point: 212-214 C; IR (KBr): 2922, 2777, 1874, 1724, 1585, 1500,
1413, 1357, 1267, 1155, 1126, 1056, 983, 945, 902, 810, 773, 732, 688, 646. cm-1 ;1
H NMR
CDCl
3):
(ss, 3H, CH3),
(ss, 3H, CH3),
(ss, 2H,
4.09
(400 MHz,
δ
ppm: 3.38
3.84
CH2), 6.35-6.33 (d, J=8 Hz, 1H, Ar-CH), 7.08-7.06 (t,
Hz, 1H, Ar-CH), 7.36-7.24 (m,
J= 8
4H, Ar-CH), 7.57-7.54 (d, J=12 Hz, 2H, aryl CH);13C NMR (100 MHz, CDCl3):
δ
ppm: 28.4,

ACCEPTED MANUSCRIPT
30.3, 39.2, 76.7, 77.0, 77.3, 107.2, 115.7, 115.9, 122.5, 124.6, 124.7, 124.9, 125.2, 125.4,
127.3, 127.6, 128.8, 128.8, 130.2, 130.3, 130.4, 138.3, 140.4, 140.6, 150.7, 151.2, 157.6, 160.0,
161.0, 169.8. HRMS (ESI/TOF-Q): m/z M+ Calculated for C22H16FN3O2 373.3797;
Found.373.3792.
Acknowledgements
SM thanks VIT University for providing financial support through research associate ship. We
also thank VIT-SIF, Chemistry department-IIT Madras for NMR and Single Crystal X-ray
diffraction facilities. The authors thank Dr. R. Srinivasan, SSL-VIT for language editing.
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ACCEPTED MANUSCRIPT
Table 1. Optimization of reaction conditions for the synthesis of benzo[f]pyrimido[4,5-b]quinoline
(4a) and indeno-pyrido[2,3-d]pyrimidine (5a).
Table-2. Substrate scope with ketones and active methylene compounds
Table 3. Optical properties of 4a-j and 5a-j in CH3CN Solvens.
Table 4. UV-Visible Absorption and Fluorescence Properties of 4a-f in various solvents.
Table 5. UV-Visible Absorption and Fluorescence Properties of 5a-f in various solvents.
Table 6. Electrochemical Data of 4a-f and 5a-f in Acetonitrile solution with 100 mM TBAFP6 at a
scan Rate of 50 mVs

ACCEPTED MANUSCRIPT
Table 1. Optimization of reaction conditions for the synthesis of benzo[f]pyrimido[4,5-b]quinoline
(4a) and indeno-pyrido[2,3-d]pyrimidine (5a).
Entry
Solvent
Catalyst
(mol%)
Additive
1.0 equiv
Time (h)
Yield %
(4a, 5a) a, b
1
2
3
4
5
6
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
I2(15)
FeCl3(15)
-
-
-
-
-
-
24
24
24
48
48
48
30, 24
20, 16
44, 41
15, 22
17, nd
23, nd
p-TSA (15)
ZnCl2(15)
CuBr(15)
Cu(OAC)2(15)
7
8
Ethanol
Ethanol
CuSO4(15)
NiCl2(15)
-
-
48
48
11, nd
36, 22
9
Ethanol
CAN(15)
-
48
47, 45
10
11
12
13
14
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
SnCl2 (5)
SnCl2 (10)
SnCl2 (15)
SnCl2 (20, 30)
SnCl2(15)
-
24
16
16
16
24
52, 54
61, 57
66, 58
66, 50
58, 62
-
-
-
HCl
15
16
Ethanol
Ethanol
SnCl2 (15)
SnCl2 (15)
Piperidine
TEA
24
24
60, 64
58, 67
17
18
19
20
Ethanol
Ethanol
Ethanol
Ethanol
SnCl2 (15)
SnCl2(15)
SnCl2(15)
SnCl2(15)
Na2CO3
K2CO3
TFA
24
24
24
16
62, 66
69, 70
74, 78
81, 84
AcOH
21
22
23
24
Isopropanol
DMF
SnCl2(15)
SnCl2(15)
SnCl2(15)
SnCl2(15)
AcOH
AcOH
AcOH
AcOH
16
16
16
16
80, 82
65, 49
15, 9
THF
CHCl3
10, 7
25
26
CAN
SnCl2(15)
SnCl2(15)
AcOH
AcOH
16
16
23, 6
Nd
Water
a Reagents and conditions: 1 (0.003 mmol), 2a-j (0.003 mmol) and 3a-b (0.003 mmol), solvents
(20 ml), b isolated yields