An efficient in-situ reduction and cyclization reaction for the synthesis of 9-aryl-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one, 11-aryl-1,6,7,8,9,11-hexahydro-10H-pyrazolo [3,4-a]acridin-10-one, and 11-aryl-3,6,7,8,9,11-hexahydro-10H-imidazo[4,5-a]acridin-10-one derivatives

Article abstract of DOI:10.1016/j.tet.2017.10.040

An efficient in-situ reduction and cyclization reaction was reported from the aromatic aldehydes, 6-nitro-1H-indazole (5-nitrobenzimidazole), and 2,2-dimethyl-1,3-dioxane-4,6-dione (1,3-cyclohexanedione or dimedone) to synthesize 9-aryl-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one, 11-aryl-1,6,7,8,9,11-hexahydro-10H-pyrazolo [3,4-a]acridin-10-one, and 11-aryl-3,6,7,8,9,11-hexahydro-10H-imidazo[4,5-a]acridin-10-one derivatives in the presence of SnCl₂·2H₂O in THF medium. The advantages of this method are mild conditions, convenient manipulation, high yields and wide range of substrates.

Full text of DOI:10.1016/j.tet.2017.10.040

Accepted Manuscript
An efficient in-situ reduction and cyclization reaction for the synthesis of 9-
aryl-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one, 11-aryl-1,6,7,8,9,11-
hexahydro-10H-pyrazolo [3,4-a]acridin-10-one, and 11-aryl-3,6,7,8,9,11-
hexahydro-10H-imidazo[4,5-a]acridin-10-one derivatives
Lirong Yan, Qingyang Li, Hui Xu, Zhongyu Xu, Qiuyu Yu, Yaqi Qin, Liangce Rong
PII:
S0040-4020(17)31068-2
10.1016/j.tet.2017.10.040
TET 29043
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 11 August 2017
Revised Date: 12 October 2017
Accepted Date: 16 October 2017
Please cite this article as: Yan L, Li Q, Xu H, Xu Z, Yu Q, Qin Y, Rong L, An efficient in-situ reduction
and cyclization reaction for the synthesis of 9-aryl-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-
one, 11-aryl-1,6,7,8,9,11-hexahydro-10H-pyrazolo [3,4-a]acridin-10-one, and 11-aryl-3,6,7,8,9,11-
hexahydro-10H-imidazo[4,5-a]acridin-10-one derivatives, Tetrahedron (2017), doi: 10.1016/
j.tet.2017.10.040.
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ACCEPTED MANUSCRIPT
An efficient in-situ reduction and cyclization reaction for the synthesis of
9-aryl-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one,
11-aryl-1,6,7,8,9,11-hexahydro-10H-pyrazolo
[3,4-a]acridin-10-one,
and
11-aryl-3,6,7,8,9,11-hexahydro-10H-imidazo[4,5-a]acridin-10-one derivatives
Lirong Yanǂ, Qingyang Liǂ, Hui Xu, Zhongyu Xu, Qiuyu Yu, Yaqi Qin, Liangce Rong*
Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials; School of
Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu, P. R.
China
Telephone Number: 86-516-83500349
Fax Number: 86-516-83403164
*E-mail: lcrong@jsnu.edu.cn
An efficient in-situ reduction and cyclization reaction for the synthesis of
9-aryl-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one,
11-aryl-1,6,7,8,9,11-hexahydro-10H-pyrazolo[3,4-a]acridin-10-one,
and
11-aryl-3,6,7,8,9,11-hexahydro-10H-imidazo[4,5-a]acridin-10-one derivatives
Lirong Yanǂ, Qingyang Liǂ, Hui Xu, Zhongyu Xu, Qiuyu Yu, Yaqi Qin, Liangce Rong*
Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials; School of
Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu, P. R.
China
E-mail: lcrong@jsnu.edu.cn
O
O
CHO
O
R1
+
R2
+
O
O
O
R2
THF 80 oC
SnCl2 2H2O
H
N
N
N
H
NO2
N
NO2
R1
R1
R1
N
N
O
HN
NH
O
N
NH
R2
N
H
6
N
O
N
H
8
R2
H
4
Simple reagents High yields 42 examples
Wide range of substrates Reduction in situ to cyclization

ACCEPTED MANUSCRIPT
An efficient in-situ reduction and cyclization reaction for the synthesis of
9-aryl-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one,
11-aryl-1,6,7,8,9,11-hexahydro-10H-pyrazolo
[3,4-a]acridin-10-one,
and
11-aryl-3,6,7,8,9,11-hexahydro-10H-imidazo[4,5-a]acridin-10-one derivatives
Lirong Yanǂ, Qingyang Liǂ, Hui Xu, Zhongyu Xu, Qiuyu Yu, Yaqi Qin, Liangce Rong*
Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials; School of
Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu, P. R.
China
Telephone Number: 86-516-83500349
Fax Number: 86-516-83403164
The authorsǂ Lirong Yan and Qingyang Li contributed equally to this article.
*E-mail: lcrong@jsnu.edu.cn
1

ACCEPTED MANUSCRIPT
An efficient in-situ reduction and cyclization reaction for the synthesis of
9-aryl-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one,
11-aryl-1,6,7,8,9,11-hexahydro-10H-pyrazolo
[3,4-a]acridin-10-one,
and
11-aryl-3,6,7,8,9,11-hexahydro-10H-imidazo[4,5-a]acridin-10-one derivatives
Lirong Yanǂ, Qingyang Liǂ, Hui Xu, Zhongyu Xu, Qiuyu Yu, Yaqi Qin, Liangce Rong*
Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials; School of
Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu, P. R.
China
Telephone Number: 86-516-83500349
Fax Number: 86-516-83403164
The authorsǂ Lirong Yan and Qingyang Li contributed equally to this article.
*E-mail: lcrong@jsnu.edu.cn
Abtracts An efficient in-situ reduction and cyclization reaction was reported from the aromatic
aldehydes, 6-nitro-1H-indazole (5-nitrobenzimidazole), and 2,2-dimethyl-1,3-dioxane-4,6-dione
(1,3-cyclohexanedione or dimedone)
to
synthesize
9-aryl-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one,
11-aryl-1,6,7,8,9,11-hexahydro-10H-pyrazolo
[3,4-a]acridin-10-one,
and
11-aryl-3,6,7,8,9,11-hexahydro-10H-imidazo[4,5-a]acridin-10-one derivatives in the presence of
SnCl2·2H2O in THF medium. The advantages of this method are mild conditions, convenient
manipulation, high yields and wide range of substrates.
Keywords
pyrazolo[3,4-f]quinoline,
imidazo[4,5-a]acridin-10-one,
in-situ
reduction,
6-nitro-1H-indazole, 5-nitrobenzimidazole
1. Intruduction
Dihydroquinolin-2-one1 core structure is a key scaffold, which not only exists in a large number of
natural products, but also in important drug candidates with various biological and
pharmacological activities, such as antiviral, antitumoral, antibacterial, antiatherosclerotic, and so
on2. Acridines are the other important nitrogen containing heterocycles and have attracted
considerable attention due to their important biological and medicinal activities3. For example
(Figure 1), compound A is a strong inhibitor of HIV-1 reverse transcriptase4, and B (carteolol) is a
b-adrenergic blocking agent5. Compound C is a PDE3 phosphodiesterase inhibitor for the
2

ACCEPTED MANUSCRIPT
treatment of peripheral vascular disease6. In addition, Compound D is the most potent combined
glycine/NMDA-AMPA antagonist7. E (porflavine) has been approved by the FDA as a drug
against many gram-positive bacteria8. F is an anticancer acridine derivative and has already been
applied in phase II clinical trial9.
HO
N
H
N
N
N
F3C
N
O
Cl
O
O
O
N
NO2
O
N
4
N
N
H
N
O
H
H
A (inhibitor of HIV-1
reverse transcriptase)
C (cilostazol)
B (carteolol)
N(CH3)2
N
NO2
H3CO
NH2
H2N
N
Cl
N
O
N
H
H
NO2
E (porflavine)
F (anticancer compound)
D (NMDA antagonist)
Figure 1. Pharmaceuticals containing the dihydroquinolin-2-one and acridine structures.
Several methods for the construction dihydroquinolin-2-one structure have been developed. For
instance, Pd-catalyzed reduction-cyclization reaction and cyclopropane ring expansion reaction
have been already reported10. Rh-mediated 1,4-addition reaction11, and Au-catalyzed cyclization
have also been performed12. In addition, radical reaction was also reported to successfully
synthesize quinolin-2(1H)-one derivatives13. However, the disadvantages of these reported
processes are obvious, such as dangerous or toxic oxide reagents, high temperature, strong acid
conditions, low yields, expensive metal catalysts, or difficulty in separation. Therefore, the
development of an efficient and facile method for the synthesis of quinolin-2(1H)-one derivatives
is desirable. Herein, we plan to report an efficient and new process to synthesize title compounds
from in-situ reduction and cyclization reaction used SnCl2·2H2O as reductant.
3

ACCEPTED MANUSCRIPT
Aromatic nitro compounds are the important industrial products, and they are also the
precursors for the synthesis of many organic compounds. Studies showed the reduction of nitro
aromatics could lead to different versatile products. Although the reduction of aromatic nitro
compounds has been achieved by a large number of methods,14 due to simple operation, mild
condition, low value, easy separation, stannous chloride hydrate (SnCl2·2H2O) is still an effective
catalyst used to reduce nitro compounds15. Therefore, this paper focuses on synthesizing
quinolin-2(1H)-one and acridine derivatives from the in-situ reduction reaction of
6-nitro-1H-indazole and 5-nitrobenzimidazole under SnCl2·2H2O/THF medium.
2. Results and Discussion
At the beginning of our research, we selected benzaldehyde 1a, 6-nitro-1H-indazole 2, and
2,2-dimethyl-1,3-dioxane-4,6-dione 3 as starting reactants to optimize the experimental conditions
for
the
expected
reductive
cyclization
reaction
for
the
synthesis
of
9-phenyl-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one 4a (Scheme 1). The results are
summarized in Table 1. As shown in Table 1, we first investigated the model reaction in different
organic solvents (entries 1-5) and found that THF was the best solvent for this synthesis. Next, we
studied the effect of different temperatures and ratio of 2/SnCl2·2H2O. The results showed that at
o
80 C temperature the reaction carried out smoothly with higher yield (entries 6, 7). Then, the
o
influence of the ratio of 2/SnCl2· 2H2O was also evaluated at 80 C (entries 8-10), and the best
result was found in THF using the ratio of 2/SnCl2·2H2O as 1:3. Of course, we also find that the
appropriate reaction time is about 5 h, and the longer reaction time did not lead to higher product
yield (entries 11, 12). We also tried another reduction system (Fe-HCl-EtOH), but the longer
reaction time was needed to obtain ideal results (entries 13-16). So, we still used SnCl2·2H2O
system.
Scheme 1. Synthesis of 4a under screening conditions.
4

ACCEPTED MANUSCRIPT
Table 1. Optimization of reaction conditions for synthesis of 4aa.
Ratio
Entry
Solvent
Temperature/oC
Time (h)
Yield (%)b
(2/SnCl2·H2O)
1
2
THF
EtOH
MeCN
CHCl3
DMF
THF
50
50
50
50
50
60
80
80
80
80
80
80
80
80
80
80
1:2
5
5
56
1:2
45
3
1:2
5
36
4
1:2
5
32
5
1:2
5
24
6
1:2
5
61
7
THF
1:2
5
75
8
THF
1:3
5
89
9
THF
1:4
1:5
5
87
10
11
12
13
14
15
16
THF
5
88
THF
1:3
6
87
THF
1:3
7
86
EtOH
EtOH
EtOH
EtOH
1:3 [Fe-HCl (1mL)]
1:3 [Fe-HCl (1mL)]
1:3 [Fe-HCl (1mL)]
1:3 [Fe-HCl (1mL)]
7
55
10
12
15
63
76
81
aReaction condition: Benzaldehyde 1a (1 mmol), 6-nitro-1H-indazole
2,2-dimethyl-1,3-dioxane-4,6-dione 3 (1 mmol), Solvent (6 mL).
bIsolated Yields.
2
(1 mmol), and
Under the optimal reaction conditions, in order to produce more quinolin-2(1H)-one derivatives,
different aromatic aldehydes, either bearing electron-withdrawing groups (F-, Cl-, Br-) or
electron-donating groups (such as Me-, MeO-, or OH-), were applied in this synthesis, and the
corresponding products 9-aryl-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one 4a-4y were
obtained with high yields (Scheme 2). According to the reaction result, we could conclude that the
properties and position of substituents have no obvious effect on yields. In this research, 25 new
quinolin-2(1H)-one derivatives were successfully synthesized. The results are listed in Table 2.
Scheme 2. Synthesis of compound 4.
5

ACCEPTED MANUSCRIPT
Table 2. The synthetic results of compound 4a.
Entry
1
R
Time (h)
Product
4a
4b
4c
Yield (%)b
89
H
5
5
5
5
4
4
4
4
3
3
3
3
4
4
2
4
5
5
5
5
5
5
5
5
3
2
2-F
88
3
2-Cl
83
4
3-Cl
4d
4e
80
5
4-Cl
89
6
2,3-Cl2
4f
91
7
2,4-Cl2
4g
4h
4i
90
8
2-Br
87
9
2-Br-3-F
2-Br-4-F
2-Br-5-F
2-Br-5-Cl
2-Br-4-CH3
2-Br-4,5-(CH3)2
2-Br-5-CH3O
4-Br
86
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
4j
90
4k
4l
91
90
4m
4n
4o
4p
4q
4r
85
83
86
87
4-CH3
90
3,4-(CH3)2
2-CH3O
4-CH3O
2,5-(CH3O)2
3,4,5-(CH3O)3
3,4-(OCH2O)-
3-OH
86
4s
81
4t
87
4u
4v
4w
4x
4y
86
84
85
81
4-OH
88
aReaction condition: Aromatic aldehyde
1
(1 mmol), 6-nitro-1H-indazole
2
(1 mmol),
o
2,2-dimethyl-1,3-dioxane-4,6-dione 3 (1 mmol), SnCl2·2H2O (3 mmol), THF (6 mL), 80 C, reaction time (3-5 h,
monitored reactions by TLC).
bIsolated Yields.
To explore the generality of this protocol, we also tested the reaction of aromatic aldehyde,
6-nitro-1H-indazole, and 1,3-cyclohexanedione or dimedone under the preferred condition
(Scheme 3). It was found that the reactions were all performed very well, and corresponding
products 11-aryl-1,6,7,8,9,11-hexahydro-10H-pyrazolo [3,4-a]acridin-10-one 6a-6l were gained
with excellent yields. Similarly, the nature of the substituents on the aromatic aldehyde had little
effect on the result of the reaction. The results were listed in Table 3.
6

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R1
O
N
CHO
O
HN
SnCl2 2H2O
R2
N
THF 80 oC
+
NO2
+
R1
R2
N
O
H
R2
N
H
6
R2
1
2
5
Scheme 3. Synthesis of compound 6.
Table 3. The synthetic results of compound 6a
Entry
1
R1
R2
Time (h)
Product
6a
Yield (%)b
4-F
H
7
7
6
8
6
7
7
6
6
6
7
7
87
84
81
86
83
89
85
87
86
87
84
85
2
4-Cl
H
6b
6c
3
3-Br
H
4
4-CH3
3,4-(OCH2O)
4-OH
4-H
H
6d
6e
5
H
6
H
6f
7
CH3
CH3
CH3
CH3
CH3
CH3
6g
8
4-F
6h
6i
9
4-Cl
10
11
12
4-Br
6j
4-CH3
4-CH3O
6k
6l
aReaction condition: Aromatic aldehyde 1 (1 mmol), 6-nitro-1H-indazole 2 (1 mmol), 1,3-cyclohexanedione or
o
dimedone 5 (1 mmol), SnCl2·2H2O (3 mmol), THF (6 mL), 80 C, reaction time (6-8 h, monitored reactions by
TLC).
bIsolated Yields.
Next, 5-nitrobenzimidazole was also tested in this synthetic strategy. To our delight, the
corresponding products 11-aryl-3,6,7,8,9,11-hexahydro-10H-imidazo[4,5-a]acridin-10-one were
successfully obtained with good yields form in-situ reduction and cyclization reaction of
5-nitrobenzimidazole, aromatic aldehyde and dimedone (Scheme 4). This is another effective
method of synthesis of acridine compounds. The results were listed in Table 4.
Scheme 4. Synthesis of compound 8.
7

ACCEPTED MANUSCRIPT
Table 4. The synthetic results of compound 8a
Entry
R
Time (h)
Product
8a
Yields (%)b
1
2
3
4
5
4-F
5
6
6
5
6
86
83
87
88
85
3-Br
8b
4-CH3
4-OCH3
3,4-(OCH2O)
8c
8d
8e
aReaction condition: Aromatic aldehyde 1 (1 mmol), dimedone 5 (1 mmol), 5-nitrobenzimidazole 7 (1 mmol),
SnCl2·2H2O (3 mmol), THF (6 mL), 80 oC, reaction time (5-6 h, monitored reactions by TLC).
bIsolated Yields.
1
All the structures of the products were characterized by H NMR, 13C NMR, IR, and HRMS.
Moreover, compound 4c was further confirmed by X-ray diffraction analysis (Figure 2).
According to the structures of the products, we provided a possible mechanism in Figure 3. Firstly,
6-nitro indazole was reduced to 6-aminoindazole A. At same time, the Knoevenagel product B
was produced from aromatic aldehyde and 2,2-dimethyl-1,3-dioxane-4,6-dione. Then,
6-aminoindazole A reacted with intermediate B to obtain intermediate C. Intermediate D is the
tautomer of C. And then, E was formed from the intramolecular cyclization of intermediate D.
Finally, because intermediate E losed a molecule of carbon dioxide and acetone, the product 4 was
obtained. The synthetic process of products 6 and 8 is the same as that of product 4. The difference
is that their final step reaction loses a molecule of water (Figure 4).
In order to proof our hypothesis, the reduction reaction of 6-nitroindazole was first performed
and the reduction product A was successfully obtained (Supporting information, Fig. 85). Then,
the reaction of A, benzaldehyde and 2,2-dimethyl-1,3-dioxane-4,6-dione was carried out under
screened condition. As expected, the product 4a was obtained with 85% yield (Scheme 5). This
fully shows that the provided mechanism is credible.
8

ACCEPTED MANUSCRIPT
Figure 2. The molecular structure of compound 4c.
Figure 3. The possible reaction mechanism of product 4.
9

ACCEPTED MANUSCRIPT
Figure 4. The possible reaction mechanism of product 6.
Scheme 5. The controlled reaction of 4a.
3. Conclusion
In summary, an efficient in-situ reduction and cyclization reaction was reported to synthesize
9-aryl-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one,
11-aryl-1,6,7,8,9,11-hexahydro-10H-pyrazolo[3,4-a]acridin-10-one,
and
11-aryl-3,6,7,8,9,11-hexahydro-10H-imidazo[4,5-a]acridin-10-one derivatives promoted by
SnCl2·2H2O in THF medium. The other advantages of this method are the easily accessible
starting materials, convenient manipulation, high yields and wide range of substrates. Moreover,
this research provided an alternative approach for the synthesis of quinolin-2(1H)-one and acridine
derivatives.
10

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4. Experimental
4.1 General methods
All reagents were purchased from the Meryer and Sigma-Aldrich chemical companies and used
without further purification. Melting points were determined on XT-5 microscopic melting-point
apparatus and were uncorrected. IR spectra were recorded on a FT Bruker Tensor 27 spectrometer.
1H NMR and 13C NMR spectra were obtained from solution in DMSO-d6 using a Bruker-400
spectrometer. HRMS spectra were obtained with a Bruker microTOF-Q 134 instrument. X-ray
diffractions were recorded on a Siemens P4 or Simart-1000 diffractometer.
4.2
9-aryl-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one,
11-aryl-1,6,7,8,9,11-hexahydro-10H-pyrazolo[3,4-a]acridin-10-one,
11-aryl-3,6,7,8,9,11-hexahydro-10H-imidazo[4,5-a]acridin-10-one derivatives
Aromatic aldehyde 1 (1 mmol), 6-nitro-1H-indazole 2 or 5-nitrobenzimidazole 7 (1 mmol),
General
procedure
for
the
synthesis
of
and
2,2-dimethyl-1,3-dioxane-4,6-dione 3 or 1,3-cyclohexanedione or dimedone
5 (1 mmol),
SnCl2·2H2O (3 mmol), and THF (6 mL) were put into a 25-mL round-bottom flask. Then, the
o
mixture was stirred at 80 C about 3-8 h (monitored reactions by TLC). After completion the
reaction, the solution was allowed to cool and the pH was made slightly basic (pH 8) by addition
of 5% aqueous NaHCO3. The mixture was transferred to a separatory funnel, and was extracted
with 3x15 mL of ethyl acetate. Organics were combined and washed thoroughly with saturated
NaCl (aq), dried over anhydrous Na2SO4, and filtered through Celite. Following reduction of the
solvent in vacuo, the material remaining was purified by crystallization from DMF or EtOH to
give the pure products 4, 6 and 8.
4.2.1 9-Phenyl-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4a)
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3442, 1675, 1618, 1495, 1385, 1075, 950, 845, 708,
1
654, 555, 465; H NMR (400 MHz, DMSO-d6) (δ, ppm): 13.01 (s, 1H, NH), 10.34 (s, 1H, NH),
7.98 (s, 1H, ArH), 7.62 (d, J = 8.8 Hz, 1H, ArH), 7.26 (t, J = 7.6 Hz, 2H, ArH), 7.19 (d, J = 7.2 Hz,
1H, ArH), 7.14 (d, J = 7.6 Hz, 2H, ArH), 6.84 (d, J = 8.4 Hz, 1H, ArH), 4.69 (d, J = 6.8 Hz, 1H,
CH), 3.18 (dd, J1 = 16.4 Hz, J2 = 7.6 Hz, 1H, HCH), 2.67 (d, J = 16.0 Hz, 1H, HCH); 13C NMR
(100 MHz, DMSO-d6) (δ, ppm): 169.2, 142.6, 139.1, 136.5, 134.6, 129.0, 127.3, 127.2, 120.6,
11

ACCEPTED MANUSCRIPT
119.9, 111.9, 106.0, 38.6, 36.9; HRMS (ESI-TOF) m/z calculated for C16H13N3NaO: 286.0956,
found [M+Na]+: 286.0964.
4.2.2 9-(2-Fluorophenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4b)
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3442, 1675, 1495, 1385, 1075, 950, 845, 708, 654,
503, 465; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 13.02 (s, 1H, NH), 10.41 (s, 1H, NH), 7.99 (s,
1H, ArH), 7.70 (d, J = 8.4 Hz, 1H, ArH), 7.55 (d, J = 7.6 Hz, 1H, ArH), 7.25 (t, J = 7.6 Hz, 1H,
ArH), 7.10 (t, J = 7.6 Hz, 1H, ArH), 6.89 (d, J = 8.4 Hz, 1H, ArH), 6.42 (d, J = 7.6 Hz, 1H, ArH),
4.97 (d, J = 7.2 Hz, 1H, CH), 3.21 (dd, J1 = 16.0 Hz, J2 = 7.6 Hz, 1H, HCH), 2.70 (d, J = 16.0 Hz,
1H, HCH); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 168.6, 138.8, 138.2, 137.8, 134.6, 133.6,
130.7, 129.3, 128.1, 127.8, 121.4, 120.2, 111.8, 104.0, 36.3, 34.9; HRMS (ESI-TOF) m/z
calculated for C16H12FN3NaO: 304.0862, found [M+Na]+: 304.0875.
4.2.3 9-(2-Chlorophenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4c)
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3218, 3087, 1682, 1572, 1442, 1349, 1237, 1164,
1037, 853, 757, 720, 659; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 13.02 (s, 1H, NH), 10.42 (s,
1H, NH), 8.00 (s, 1H, ArH), 7.70 (d, J = 8.4 Hz, 1H, ArH), 7.54 (d, J = 8.0 Hz, 1H, ArH), 7.25 (t,
J = 7.2 Hz, 1H, ArH), 7.09 (t, J = 7.6 Hz, 1H, ArH), 6.89 (d, J = 8.4 Hz, 1H, ArH), 6.42 (d, J = 7.2
Hz, 1H, ArH), 4.98 (d, J = 6.8 Hz, 1H, CH), 3.21 (dd, J1 = 16.0 Hz, J2 = 7.6 Hz, 1H, HCH), 2.71
(d, J = 16.0 Hz, 1H, HCH); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 168.6, 138.8, 138.2, 137.8,
134.6, 133.8, 130.7, 129.3, 128.1, 127.8, 121.4, 120.2, 111.8, 104.0, 36.3, 34.9; HRMS (ESI-TOF)
m/z calculated for C16H12ClN3NaO: 320.0567, found [M+Na]+: 320.0569.
4.2.4 9-(3-Chlorophenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4d)
White solid, m.p. 268-270 °C, IR (KBr) (ν, cm-1): 3277, 3075, 1678, 1472, 1385, 1077, 950, 849,
704, 653, 645, 566, 525; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 13.05 (s, 1H, NH), 10.41 (s,
1H, NH), 8.01 (s, 1H, ArH), 7.65 (d, J = 8.4 Hz, 1H, ArH), 7.30 (t, J =7.6 Hz, 2H, ArH), 7.22 (s,
1H, ArH), 7.08 (d, J = 6.4 Hz, 1H, ArH), 6.87 (d, J = 8.4 Hz, 1H, ArH), 4.71 (d, J = 6.8 Hz, 1H,
CH), 3.21 (dd, J1= 16.4 Hz, J2 = 7.2 Hz, 1H, HCH), 2.70 (d, J = 16.0 Hz, 1H, HCH); 13C NMR
(100 MHz,DMSO-d6) (δ, ppm): 169.0, 145.1, 139.0, 136.6, 134.7, 133.6, 131.0, 127.3, 126.0,
121.0, 120.0, 112.0, 105.3, 38.4, 36.7; HRMS (ESI-TOF) m/z calculated for C16H12ClN3NaO:
320.0567, found [M+Na]+: 320.0580.
12

ACCEPTED MANUSCRIPT
4.2.5 9-(4-Chlorophenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4e)
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3127, 1681, 1618, 1491, 1400, 1262, 1093, 1014,
1
945, 925, 854, 833; H NMR (400 MHz, DMSO-d6) (δ, ppm): 13.03 (s, 1H, NH), 10.38 (s, 1H,
NH), 7.99 (s, 1H, ArH), 7.63 (d, J = 8.4 Hz, 1H, ArH), 7.33 (d, J = 8.4 Hz, 2H, ArH), 7.14 (d, J =
8.4 Hz, 2H, ArH ), 6.85 (d, J = 8.4 Hz, 1H, ArH), 4.69 (d, J = 6.8 Hz, 1H, CH), 3.19 (dd, J1 = 16.4
Hz, J2 = 7.2 Hz, 1H, HCH), 2.67 (d, J = 16.0 Hz, 1H, HCH); 13C NMR (100 MHz, DMSO-d6) (δ,
ppm): 169.1, 141.5, 139.0, 136.5, 134.6, 131.9, 129.2, 129.0, 120.9, 119.9, 112.0, 105.5, 38.5,
36.4; HRMS (ESI-TOF) m/z calculated for C16H12ClN3NaO: 320.0567, found [M+Na]+:
320.0573.
4.2.6 9-(2,3-Dichlorophenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4f)
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3437, 1666, 1628, 1415, 1389, 1226, 1168, 1011,
1
926, 850, 653, 569; H NMR (400 MHz, DMSO-d6) (δ, ppm): 13.04 (s, 1H, NH), 10.47 (s, 1H,
NH), 8.00 (s, 1H, ArH), 7.95 (s, 1H, ArH), 7.71 (d, J = 8.5 Hz, 1H, ArH), 7.52 (d, J = 7.9 Hz, 1H,
ArH), 7.13 (t, J = 7.9 Hz, 1H, ArH), 6.91 (d, J = 8.5 Hz, 1H, ArH), 6.41 (d, J = 7.7 Hz, 1H, ArH),
5.02 (d, J = 7.4 Hz, 1H, CH), 3.26 (dd, J1 = 16.2 Hz, J2 = 7.7 Hz, 1H, HCH), 2.70 (d, J = 16.0 Hz,
1H, HCH); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 168.4, 141.0, 138.8, 137.8, 134.7, 133.2,
131.8, 129.7, 128.6, 126.7, 121.6, 120.2, 111.9, 103.8, 36.2, 35.8; HRMS (ESI-TOF) m/z
calculated for C16H11Cl2N3NaO: 354.0177, found [M+Na]+: 354.0165.
4.2.7 9-(2,4-Dichlorophenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4g)
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3444, 1666, 1632, 1461, 1384, 1051, 928, 865, 816,
669; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 13.04 (s, 1H, NH), 10.46 (s, 1H, NH), 8.01 (s, 1H,
ArH), 7.73-7.70 (m, 2H, ArH), 7.22 (dd, J1 = 8.4 Hz, J2 = 2.4 Hz, 1H, ArH), 6.91 (d, J = 8.4 Hz,
1H, ArH), 6.42 (d, J = 8.4 Hz, 1H, ArH), 4.95 (d, J = 7.2 Hz, 1H, CH), 3.23 (dd, J1= 16.4 Hz, J2 =
7.6 Hz, 1H, HCH), 2.68 (d, J = 16.0 Hz, 1H, HCH); 13C NMR (100 MHz, DMSO-d6) (δ, ppm):
169.4, 156.6, 139.1, 136.3, 134.5, 132.7, 128.3, 120.4, 119.9, 115.7, 111.9, 106.6, 38.9, 36.1;
HRMS (ESI-TOF) m/z calculated for C16H11Cl2N3NaO: 354.0177, found [M+Na]+: 354.0191.
4.2.8 9-(2-Bromophenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4h)
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3432, 1672, 1438, 1353, 1307, 1228, 1162, 1027,
925, 854, 715, 665, 519, 442; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 13.05 (s, 1H, NH), 10.44
13

ACCEPTED MANUSCRIPT
(s, 1H, NH), 8.00 (s, 1H, ArH), 7.73-7.70 (m, 2H, ArH), 7.16-7.11 (m, 2H, ArH), 6.91 (d, J = 8.8
Hz, 1H, ArH), 6.43 (d, J = 7.2 Hz, 1H, ArH), 4.91 (d, J = 7.2 Hz, 1H, CH), 3.20 (dd, J1 = 16.4 Hz,
J2 = 7.6 Hz, 1H, HCH), 2.76 (d, J = 16.0 Hz, 1H, HCH); 13C NMR (100 MHz, DMSO-d6) (δ,
ppm): 168.6, 139.6, 138.8, 137.8, 134.6, 134.1, 129.5, 128.3, 128.3, 124.6, 121.4, 120.2, 111.8,
104.2, 37.0, 36.2; HRMS (ESI-TOF) m/z calculated for C16H12BrN3NaO: 364.0061, found
[M+Na]+: 364.0069.
4.2.9 9-(2-Bromo-3-fluorophenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4i)
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3432, 1735, 1670, 1637, 1570, 1508, 1437, 1158,
1
1035, 581, 473; H NMR (400 MHz, DMSO-d6) (δ, ppm):13.03 (s, 1H, NH), 10.45 (s, 1H, NH),
8.01 (d, J = 1.2 Hz, 1H, ArH), 7.72 (d, J = 8.4 Hz, 1H, ArH), 7.19-7.26 (m, 2H, ArH), 6.90 (d, J =
8.8 Hz, 1H, ArH), 6.28 (d, J = 7.2 Hz, 1H, ArH), 4.94 (d, J = 7.2 Hz, 1H, CH), 3.25 (dd, J1 = 16.4
Hz,J2 = 7.6 Hz, 1H, HCH), 2.76 (d, J = 16.0 Hz, 1H, HCH); 13C NMR (100 MHz, DMSO-d6) (δ,
ppm): 168.3, 160.6, 158.2, 142.4, 138.8, 137.8, 134.7, 129.6, 129.5, 123.8, 121.6, 120.2, 115.8,
115.6, 111.9, 111.3, 111.1, 103.9, 37.0, 36.2; HRMS (ESI-TOF) m/z calculated for
C16H11BrFN3NaO: 381.9967, found [M+Na]+: 381.9975.
4.2.10 9-(2-Bromo-4-fluorophenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4j)
White solid, m.p. 267-269 °C; IR (KBr) (ν, cm-1): 3438, 1675, 1625, 1480, 1385, 1225, 1035, 927,
849, 664; 1H NMR (400 MHz, DMSO-d6) (δ, ppm):13.05 (s, 1H, NH), 10.45 (s, 1H, NH), 8.01 (d,
J = 0.8 Hz, 1H, ArH), 7.70-7.73 (m, 2H, ArH), 7.03-7.08 (m, 1H, ArH), 6.91 (d, J = 8.4 Hz, 1H,
ArH), 6.43 (dd, J1 = 8.8 Hz,J2 = 6.4 Hz, 1H, ArH), 4.88 (d, J = 7.2 Hz, 1H, CH), 3.20 (dd, J1 =
16.4 Hz, J2 = 7.6 Hz, 1H, HCH), 2.73 (d, J = 16.0 Hz, 1H, HCH); 13C NMR (100 MHz, DMSO-d6)
(δ, ppm): 168.5, 162.4, 160.0, 137.7, 136.0, 129.4 (d, JCF = 8.6 Hz), 124.7 (d, JCF = 9.6 Hz), 121.5,
121.3, 121.1, 120.2, 115.3, 115.1, 111.9, 37.0, 36.5; HRMS (ESI-TOF) m/z calculated for
C16H11BrFN3NaO: 381.9967, found [M+Na]+: 381.9973.
4.2.11 9-(2-Bromo-5-fluorophenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4k)
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3426, 1674, 1468, 1352, 1170, 1033, 927, 854, 669,
632, 579; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 13.11 (s, 1H, NH), 10.48 (s, 1H, NH), 8.03 (s,
1H, ArH), 7.79 (dd, J1 = 8.8 Hz, J2 = 5.6 Hz, 1H, ArH), 7.74 (d, J = 8.8 Hz, 1H, ArH), 7.07-7.12
(m,1H, ArH), 6.92 (d, J = 8.4 Hz, 1H, ArH), 6.11 (dd, J1 = 10.0 Hz, J2 = 2.8 Hz, 1H, ArH), 4.90 (d,
14

ACCEPTED MANUSCRIPT
J = 7.2 Hz, 1H, CH), 3.24 (dd, J1 = 16.0 Hz, J2 = 7.6 Hz, 1H, HCH), 2.74 (d, J = 16.0 Hz, 1H,
HCH); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 168.3, 163.0, 160.6, 142.4, 142.3, 137.7, 135.9,
135.8, 121.8, 120.2, 119.0, 118.9, 116.7, 116.5, 115.2, 114.9, 111.9, 37.3, 36.7; HRMS (ESI-TOF)
m/z calculated for C16H11BrFN3NaO: 381.9967, found [M+Na]+: 381.9982.
4.2.12 9-(2-Bromo-5-chlorophenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4l)
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3416, 1681, 1625, 1453, 1346, 1285, 1022, 923,
1
825, 768, 631, 558; H NMR (400 MHz, DMSO-d6) (δ, ppm):13.11 (s, 1H, NH), 10.49 (s, 1H,
NH), 8.03 (s, 1H, ArH), 7.76 (dd, J1 = 10.4 Hz, J2 = 8.4 Hz, 2H, ArH), 7.28 (dd, J1 = 8.8 Hz, J2 =
2.4 Hz, 1H, ArH), 6.92 (d, J = 8.8 Hz, 1H, ArH), 6.32 (d, J = 2.4 Hz, 1H, ArH), 4.90 (d, J = 7.2 Hz,
1H, CH), 3.25 (dd, J1 = 16.0 Hz, J2 = 7.6 Hz, 1H, HCH), 2.73 (d, J =16.0 Hz, 1H, HCH); 13C
NMR (100 MHz, DMSO-d6) (δ, ppm): 168.3, 142.0, 138.7, 137.8, 135.9, 134.8, 132.9, 129.5,
127.7, 123.0, 121.9, 120.3, 111.9, 103.5, 37.2, 36.3; HRMS (ESI-TOF) m/z calculated for
C16H11BrClN3NaO: 397.9672, found [M+Na]+: 397.9678.
4.2.13 9-(2-Bromo-4-methylphenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4m)
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3150, 3035, 1624, 1417, 1399, 1236, 1043, 925,
1
861, 818, 669; H NMR (400 MHz, DMSO-d6) (δ, ppm):13.02 (s, 1H, NH), 10.40 (s, 1H, NH),
8.00 (s, 1H, ArH), 7.70 (d, J = 8.4 Hz, 1H, ArH), 7.55 (s, 1H, ArH), 6.94 (d, J = 7.6 Hz, 1H, ArH),
6.90 (d, J = 8.4 Hz, 1H, ArH), 6.30 (d, J = 8.0 Hz, 1H, ArH), 4.86 (d, J = 7.2 Hz, 1H, CH), 3.6 (dd,
J1 = 16.4 Hz, J2 = 7.6 Hz, 1H, HCH), 2.74 (d, J = 16.0 Hz, 1H, HCH), 2.22 (s, 3H, CH3); 13C
NMR (100 MHz, DMSO-d6) (δ, ppm): 168.6, 139.3, 137.8, 136.5, 134.6, 134.3, 128.9, 128.0,
124.3, 121.3, 120.2, 111.9, 104.4, 37.2, 36.7, 20.4; HRMS (ESI-TOF) m/z calculated for
C17H14BrN3NaO: 378.0218, found [M+Na]+: 378.0231.
4.2.14 9-(2-Bromo-4,5-dimethylphenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4n)
White solid, m.p. 269-271 °C; IR (KBr) (ν, cm-1): 3428, 1687, 1627, 1435, 1382, 1213, 1067,
1
1026, 930, 803; H NMR (400 MHz, DMSO-d6) (δ, ppm):13.00 (s, 1H, NH), 10.43 (s, 1H, NH),
8.01 (d, J = 1.2 Hz, 1H, ArH), 7.71 (d, J = 8.4 Hz, 1H, ArH), 7.27 (s, 1H, ArH), 6.91 (d, J = 8.4
Hz, 1H, ArH), 6.01 (s, 1H, ArH), 4.84 (d, J = 5.6 Hz, 1H, CH), 3.76 (s, 3H, CH3), 3.30 (s, 3H,
CH3), 3.14 (dd, J1 = 16.4 Hz, J2 = 7.6 Hz, 1H, HCH), 2.72 (d, J = 15.6 Hz, 1H, HCH); 13C NMR
(100 MHz, DMSO-d6) (δ, ppm): 168.7, 149.1, 148.3, 138.9, 137.7, 134.5, 131.5, 121.4, 120.2,
15

ACCEPTED MANUSCRIPT
117.4, 114.4, 111.9, 111.8, 104.8, 56.5, 55.8, 37.4, 36.8; HRMS (ESI-TOF) m/z calculated for
C18H16BrN3NaO: 392.0374, found [M+Na]+: 392.0379.
4.2.15 9-(2-Bromo-5-methoxyphenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4o)
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3434, 3066, 1674, 1438, 1281, 1054, 927, 832, 689,
1
591, 559, 446; H NMR (400 MHz, DMSO-d6) (δ, ppm):13.06 (s, 1H, NH), 10.41 (s, 1H, NH),
8.02 (s, 1H, ArH), 7.72 (d, J = 8.4 Hz, 1H, ArH), 7.63 (d, J = 8.8 Hz, 1H, ArH), 6.90 (d, J = 8.4
Hz, 1H, ArH), 6.80 (dd, J1 = 8.8 Hz, J2 = 3.2 Hz, 1H, ArH), 5.92 (d, J = 2.8 Hz, 1H, ArH), 4.85 (d,
J = 7.2 Hz, 1H, CH), 3.53 (s, 3H, CH3), 3.19 (dd, J1 = 16.0 Hz, J2 = 7.6 Hz, 1H, HCH), 2.75 (d, J
= 14.4 Hz, 1H, HCH); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 168.5, 159.0, 140.6, 138.8,
137.8, 134.8, 134.7, 121.5, 120.2, 115.8, 114.5, 113.3, 111.8, 104.2, 55.6, 37.1, 36.9; HRMS
(ESI-TOF) m/z calculated for C17H14BrN3NaO2: 394.0167, found [M+Na]+: 394.0154.
4.2.16 9-(4-Bromophenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4p)
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3205, 3077, 1681, 1488, 1384, 1263, 1219, 1047,
1
925, 828, 715, 630, 565; H NMR (400 MHz, DMSO-d6) (δ, ppm): 13.01 (s, 1H, NH), 10.37 (s,
1H, NH), 7.99 (s, 1H, ArH), 7.63 (d, J = 8.4 Hz, 1H, ArH), 7.47 (d, J = 8.0 Hz, 2H, ArH), 7.07 (d,
J = 8.4 Hz, 2H, ArH), 6.84 (d, J = 8.4 Hz, 1H, ArH), 4.67 (d, J = 6.8 Hz, 1H, CH), 3.18 (dd, J1 =
16.4 Hz, J2 = 7.6 Hz, 1H, HCH), 2.65 (d, J = 16.0 Hz, 1H, HCH); 13C NMR (100 MHz, DMSO-d6)
(δ, ppm): 169.0, 142.0, 139.0, 136.5, 134.6, 131.9, 129.6, 120.9, 120.4, 119.9, 112.0, 105.4, 38.4,
36.4; HRMS (ESI-TOF) m/z calculated for C16H12BrN3NaO: 364.0061, found [M+Na]+:
364.0070.
4.2.17 9-(4-Methyphenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4q)
White solid, m.p. 269-271 °C; IR (KBr) (ν, cm-1): 3165, 1677, 1514, 1399, 1264, 1063, 1074, 953,
844, 822; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 13.01 (s, 1H, NH), 10.34 (s, 1H, NH), 7.99 (s,
1H, ArH), 7.61 (d, J = 8.4 Hz, 1H, ArH), 7.05 (d, J = 3.2 Hz, 4H, ArH), 6.85 (d, J = 8.4 Hz, 1H,
ArH), 4.66 (d, J = 6.4 Hz, 1H, CH), 3.16 (dd, J1 = 16.0 Hz, J2 = 6.8 Hz, 1H, HCH), 2.65 (d, J =
16.0 Hz, 1H, HCH), 2.21 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 169.3, 139.6,
139.2, 136.4, 136.3, 134.4, 129.6, 127.2, 120.5, 119.9, 112.0, 106.3, 38.7, 36.6, 21.0; HRMS
(ESI-TOF) m/z calculated for C17H15N3NaO: 300.1113, found [M+Na]+: 300.1128.
4.2.18 9-(3,4-Dimethylphenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4r)
16

ACCEPTED MANUSCRIPT
1
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3432, 3131, 1676, 1624, 1394, 926, 840, 668; H
NMR (400 MHz, DMSO-d6) (δ, ppm): 12.96 (s, 1H, NH), 10.32 (s, 1H, NH), 7.98 (s, 1H, ArH),
7.61 (d, J = 8.8 Hz, 1H, ArH), 6.99 (d, J = 7.2 Hz, 2H, ArH), 6.84 (d, J = 8.4 Hz, 1H, ArH), 6.79
(d, J = 7.6 Hz, 1H, ArH), 4.62 (d, J = 6.8 Hz, 1H, CH), 3.15 (dd, J1= 16.4 Hz, J2 = 7.6 Hz, 1H,
HCH), 2.64 (d, J = 16.0 Hz, 1H, HCH), 2.13 (s, 3H, CH3), 2.12 (s, 3H, CH3); 13C NMR (100
MHz, DMSO-d6) (δ, ppm): 169.3, 140.0, 139.1, 136.6, 136.4, 135.1, 134.5, 130.0, 128.6, 124.5,
120.5, 119.9, 111.9, 106.3, 38.8, 36.6, 20.0, 19.3; HRMS (ESI-TOF) m/z calculated for
C18H17N3NaO: 314.1269, found [M+Na]+: 314.1263.
4.2.19 9-(2-Methoxyphenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4s)
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3253, 3073, 1676, 1624, 1463, 1351, 1251, 1024,
924, 853, 757, 673, 648, 587; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.85 (s, 1H, NH), 10.26
(s, 1H, NH), 7.97 (s, 1H, ArH), 7.65 (d, J = 8.4 Hz, 1H, ArH), 7.20 (t, J = 7.6 Hz, 1H, ArH), 7.07
(d, J = 8.0 Hz, 1H, ArH), 6.86 (d, J = 8.4 Hz, 1H, ArH), 6.67 (t, J = 7.2 Hz, 1H, ArH), 6.29 (d, J =
7.2 Hz, 1H, ArH), 4.93 (d, J = 7.2 Hz, 1H, CH), 3.94 (s, 3H, CH3), 3.05 (dd, J1 = 16.4 Hz, J2 = 7.2
Hz, 1H, HCH), 2.69 (d, J = 16.0 Hz, 1H, HCH); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 169.4,
157.5, 139.0, 137.6, 134.5, 128.8, 128.7, 126.9, 120.7, 120.4, 112.0, 111.8, 111.6, 104.9, 55.9,
36.9, 32.0; HRMS (ESI-TOF) m/z calculated for C17H15N3NaO2: 316.1062, found [M+Na]+:
316.1073.
4.2.20 9-(4-Methoxyphenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4t)
White solid, m.p. 260-262 °C; IR (KBr) (ν, cm-1): 3447, 3204, 1669, 1623, 1508, 1394, 1244,
1073, 1036, 933; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 13.01 (s, 1H, NH), 10.34 (s, 1H, NH),
7.99 (s, 1H, ArH), 7.62 (d, J = 8.4 Hz, 1H, ArH), 7.07 (d, J = 8.0 Hz, 2H, ArH), 6.84 (t, J = 8.8 Hz,
3H, ArH), 4.65 (d, J = 6.8 Hz, 1H, CH), 3.67 (s, 3H, CH3), 3.15 (dd, J1 = 16.4 Hz, J2 = 7.2 Hz, 1H,
HCH), 2.66 (d, J = 16.0 Hz, 1H, HCH); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 169.4, 158.6,
139.1, 136.3, 134.5, 134.5, 128.3, 120.5, 119.9, 114.4, 112.0, 106.5, 55.5, 38.8, 36.2; HRMS
(ESI-TOF) m/z calculated for C17H15N3NaO2: 316.1062, found [M+Na]+: 316.1078.
4.2.21 9-(2,5-Dimethoxyphenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4u)
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3133, 1677, 1400, 1283, 1053, 927, 849, 724, 709,
621, 465; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.86 (s, 1H, NH), 10.26 (s, 1H, NH), 7.98 (s,
17

ACCEPTED MANUSCRIPT
1H, ArH), 7.65 (d, J = 8.4 Hz, 1H, ArH), 6.97 (d, J = 8.8 Hz, 1H, ArH), 6.86 (d, J = 8.4 Hz, 1H,
ArH), 6.76 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz, 1H, ArH), 5.83 (d, J = 2.0 Hz, 1H, ArH), 4.88 (d, J = 6.8
Hz, 1H, CH), 3.87 (s, 3H, CH3), 3.49 (s, 3H, CH3), 3.04 (dd, J1 = 16.0 Hz, J2 = 7.2 Hz, 1H, HCH),
2.67 (d, J = 16.0 Hz, 1H, HCH); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 176.1, 162.8, 159.8,
152.6, 151.5, 148.1, 143.9, 142.0, 131.9, 129.2, 119.3, 112.3, 111.1, 104.8, 36.3, 31.3, 14.5;
HRMS (ESI-TOF) m/z calculated for C18H17N3NaO3: 346.1168, found [M+Na]+: 346.1162.
4.2.22 9-(3,4,5-Trimethoxyphenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4v)
White solid, m.p. 275-277 °C; IR (KBr) (ν, cm-1): 3448, 3266, 1676, 1623, 1475, 1458, 1273,
1125, 1009, 925, 857, 794, 696, 577, 469; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 13.02 (s, 1H,
NH), 10.39 (s, 1H, NH), 7.99 (s, 1H, ArH), 7.61 (d, J = 8.4 Hz, 1H, ArH), 6.83 (d, J = 8.4 Hz, 1H,
ArH), 6.54 (s, 2H, ArH), 4.59 (d, J = 7.2 Hz, 1H, CH), 3.65 (s, 6H, CH3), 3.58 (s, 3H, CH3), 3.17
(dd, J1 = 16.0 Hz, J2 = 7.6 Hz, 1H, HCH), 2.68 (d, J = 16.0 Hz, 1H, HCH); 13C NMR (100 MHz,
DMSO-d6) (δ, ppm): 169.5, 153.3, 139.0, 138.7, 136.9, 136.25, 134.6, 120.7, 119.9, 112.0, 106.2,
104.8, 60.4, 56.2, 38.4, 37.4; HRMS (ESI-TOF) m/z calculated for C19H19N3NaO4: 376.1273,
found [M+Na]+: 376.1282.
4.2.23 9-(Benzo[d][1,3]dioxol-5-yl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4w)
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3299, 3077, 1674, 1486, 1249, 1231, 1041, 950,
1
855, 827, 649, 566, 438; H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.98 (s, 1H, NH), 10.33 (s,
1H, NH), 7.98 (s, 1H, ArH), 7.61 (d, J = 8.4 Hz, 1H, ArH), 6.83 (d, J = 8.4 Hz, 1H, ArH), 6.77 (t,
2H, J = 8.0 Hz, 2H, ArH), 6.54 (d, J = 8.0 Hz, 1H, ArH), 5.94 (d, J = 4.4 Hz, 2H, CH2), 4.60 (d, J
= 6.8 Hz, 1H, CH), 3.13 (dd, J1 = 16.0 Hz, J2 = 7.2 Hz, 1H, HCH), 2.64 (d, J = 16.0 Hz, 1H,
HCH); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 169.3, 147.9, 146.5, 139.0, 136.5, 136.3, 134.6,
120.6, 120.0, 119.9, 111.9, 108.7, 107.9, 106.2, 101.4, 38.8, 36.7; HRMS (ESI-TOF) m/z
calculated for C17H13N3NaO3: 330.0855, found [M+Na]+: 330.0867.
4.2.24 9-(3-Hydroxyphenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4x)
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3322, 1676, 1456, 1387, 1218, 1050, 925, 803, 707,
1
645, 631, 546; H NMR (400 MHz, DMSO-d6) (δ, ppm): 13.03 (s, 1H, NH), 10.36 (s, 1H, NH),
7.99 (s, 1H, OH), 7.63 (d, J = 8.4 Hz, 1H, ArH), 7.26 (t, J = 7.2 Hz, 2H, ArH), 7.17 (dd, J1 = 14.0
Hz, J2 = 7.2 Hz, 3H, ArH), 6.86 (d, J = 8.4 Hz, 1H, ArH), 4.70 (d, J = 7.2 Hz, 1H, CH), 3.19 (dd,
18

ACCEPTED MANUSCRIPT
J1 = 16.4 Hz, J2 = 7.6 Hz, 1H, HCH), 2.69 (d, J = 16.0 Hz, 1H, HCH); 13C NMR (100 MHz,
DMSO-d6) (δ, ppm): 169.3, 142.6, 139.1, 136.5, 134.6, 129.0, 127.3, 127.2, 120.7, 119.9, 112.0,
106.0, 38.6, 36.9; HRMS (ESI-TOF) m/z calculated for C16H13N3NaO2: 302.0905, found [M+Na]+:
302.0921.
4.2.25 9-(4-Hydroxyphenyl)-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one (4y)
White solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3439, 1657, 1514, 1410, 1253, 1050, 951, 855, 704,
1
658, 515, 419; H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.97 (s, 1H, NH), 10.28 (s, 1H, NH),
9.27 (s, 1H, OH), 7.98 (s, 1H, ArH), 7.60 (d, J = 8.4 Hz, 1H, ArH), 6.93 (d, J = 8.4 Hz, 2H, ArH),
6.82 (d, J = 8.4 Hz, 1H, ArH), 6.64 (d, J = 8.4 Hz, 2H, ArH), 4.58 (d, J = 6.8 Hz, 1H, CH), 3.11
(dd, J1 = 16.0 Hz, J2 = 7.2 Hz, 1H, HCH), 2.62 (d, J = 16.0 Hz, 1H, HCH); 13C NMR (100 MHz,
DMSO-d6) (δ, ppm): 168.4, 138.8, 137.8, 137.4, 134.8, 134.7, 132.9, 130.1, 129.4, 127.9, 121.6,
120.2, 111.9, 103.6, 36.6, 34.6; HRMS (ESI-TOF) m/z calculated for C16H13N3NaO2: 302.0905,
found [M+Na]+: 302.0922.
4.2.26 11-(4-Fluorophenyl)-1,6,7,8,9,11-hexahydro-10H-pyrazolo[3,4-a]acridin-10-one (6a)
Yellow solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3432, 1668, 1631, 1507, 1424, 1395, 1257, 1161,
1028, 928, 845, 763, 665, 535, 480; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.92 (s, 1H, NH),
9.72 (s, 1H, NH), 7.93 (s, 1H, ArH), 7.52 (d, J = 8.4 Hz, 1H, ArH), 7.37 (dd, J1 = 8.4 Hz, J2 = 6.0
Hz, 2H, ArH), 6.97 (t, J = 8.8 Hz, 2H, ArH), 6.88 (d, J = 8.4 Hz, 1H, ArH), 5.58 (s, 1H, CH),
2.65-2.60 (m, 2H, CH2), 2.29-2.21 (m, 2H, CH2), 1.98-1.92 (m, 1H, CH), 1.87-1.80 (m, 1H, CH);
13C NMR (100 MHz, DMSO-d6) (δ, ppm): 193.9, 162.1, 159.7, 153.8, 143.7 (d, JCF = 2.9 Hz),
139.1, 134.6, 129.6 (d, JCF = 7.9 Hz), 120.2, 119.8, 114.9 (d, JCF = 20.9 Hz), 111.8, 108.4, 106.2,
37.2, 35.0, 27.5, 21.5; HRMS (ESI-TOF) m/z calculated for C20H16FN3NaO: 356.1175, found
[M+Na]+: 356.1179.
4.2.27 11-(4-Chlorophenyl)-1,6,7,8,9,11-hexahydro-10H-pyrazolo[3,4-a]acridin-10-one (6b)
Yellow solid, m.p. 217-219 °C; IR (KBr) (ν, cm-1): 3421, 3269, 1703, 1610, 1539, 1488, 1393,
1320, 1224, 1128, 1086, 1013, 930, 738, 615; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.90 (s,
1H, NH), 9.75 (s, 1H, NH), 7.94 (s, 1H, ArH), 7.53 (d, J = 8.8 Hz, 1H, ArH), 7.36 (d, J = 8.4 Hz,
2H, ArH), 7.21 (d, J = 8.4 Hz, 2H, ArH), 6.89 (d, J = 8.4 Hz, 1H, ArH), 5.57 (s, 1H, CH), 2.63 (d,
J = 4.0 Hz, 2H, CH2), 2.29-2.18 (m, 2H, CH2), 1.98-1.92 (m, 1H, CH), 1.88-1.79 (m, 1H, CH);
19

ACCEPTED MANUSCRIPT
13C NMR (100 MHz, DMSO-d6) (δ, ppm): 193.9, 153.9, 146.4, 134.6, 130.8, 129.7, 128.2, 120.2,
119.9, 111.8, 108.1, 105.9, 37.2, 35.2, 27.5, 21.5; HRMS (ESI-TOF) m/z calculated for
C20H16ClN3NaO: 372.0880, found [M+Na]+: 372.0885.
4.2.28 11-(3-Bromophenyl)-1,6,7,8,9,11-hexahydro-10H-pyrazolo[3,4-a]acridin-10-one (6c)
Yellow solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3327, 3180, 1660, 1595, 1493, 1385, 1285, 1199,
1102, 928, 842, 788, 729, 690, 594; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.94 (s, 1H, NH),
9.77 (s, 1H, NH), 7.95 (s, 1H, NH), 7.64 (s, 1H, ArH), 7.55 (d, J = 8.4 Hz, 1H, ArH), 7.66-7.22 (m,
2H, ArH), 7.11 (t, J = 8.0 Hz, 1H, ArH), 6.89 (d, J = 8.8 Hz, 1H, ArH), 5.55 (s, 1H, CH),
2.67-2.60 (m, 2H, CH2), 2.31-2.20 (m, 2H, CH2), 1.98-1.92 (m, 1H, CH), 1.87-1.79 (m, 1H, CH);
13C NMR (100 MHz, DMSO-d6) (δ, ppm): 193.9, 154.0, 150.0, 134.7, 130.7, 130.7, 129.1, 126.9,
121.7, 120.2, 120.1, 111.8, 107.9, 37.1, 35.6, 27.5, 21.5; HRMS (ESI-TOF) m/z calculated for
C20H16BrN3NaO: 416.0374, found [M+Na]+: 416.0399.
4.2.29 11-(p-tolyl)-1,6,7,8,9,11-hexahydro-10H-pyrazolo[3,4-a]acridin-10-one (6d)
Yellow solid, m.p. 243-245 °C; IR (KBr) (ν, cm-1): 3269, 1706, 1590, 1491, 1450, 1393, 1283,
1197, 1049, 931, 852, 805,759, 638; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.86 (s, 1H, NH),
9.65 (s, 1H, NH), 7.91 (s, 1H, ArH), 7.50 (d, J = 8.4 Hz, 1H, ArH), 7.24 (d, J = 8.0 Hz, 2H, ArH),
6.93 (d, J = 8.0 Hz, 2H, ArH), 6.86 (d, J = 8.4 Hz, 1H, ArH), 5.52 (s, 1H, CH), 2.64-2.59 (m, 2H,
CH2), 2.28-2.21 (m, 2H, CH2), 2.14 (s, 3H, CH3), 1.98-1.92 (m, 1H, CH), 1.87-1.79 (m, 1H, CH);
13C NMR (100 MHz, DMSO-d6) (δ, ppm): 193.8, 153.6, 144.7, 139.2, 135.1, 134.6, 134.4, 128.8,
127.8, 120.2, 119.5, 111.8, 108.6, 106.6, 37.2, 35.2, 27.5, 21.5, 21.0; HRMS (ESI-TOF) m/z
calculated for C21H19N3NaO: 352.1426, found [M+Na]+: 352.1438.
4.2.30 11-(Benzo[d][1,3]dioxol-5-yl)-1,6,7,8,9,11-hexahydro-10H-pyrazolo[3,4-a]acridin-10-one
(6e)
Yellow solid, m.p. 269-271 °C; IR (KBr) (ν, cm-1): 3427, 3135, 1593, 1540, 1486, 1390, 1250,
1228, 1193, 1038, 929; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.87 (s, 1H, NH), 9.76 (s, 1H,
NH), 7.93 (s, 1H, ArH), 7.51 (d, J = 8.4 Hz, 1H, ArH), 6.94 (d, J = 1.6 Hz, 1H, ArH), 6.89 (d, J =
8.8 Hz, 1H, ArH), 6.78 (dd, J1 = 8.0 Hz, J2 = 1.6 Hz, 1H, ArH), 6.67 (d, J = 8.0 Hz, 1H, ArH), 5.87
(d, J = 5.6 Hz, 2H, CH2), 5.48 (s, 1H, CH), 2.68-2.58 (m, 2H, CH2), 2.29-2.21 (m, 2H, CH2),
1.97-1.91 (m, 1H, CH), 1.88-1.78 (m, 1H, CH); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 193.9,
20

ACCEPTED MANUSCRIPT
153.7, 147.2, 145.6, 141.8, 139.2, 134.5, 134.4, 120.7, 120.1, 119.6, 111.8, 108.6, 108.5, 108.1,
106.6, 101.0, 37.2, 35.3, 27.5, 21.5; HRMS (ESI-TOF) m/z calculated for C21H17N3NaO3:
382.1168, found [M+Na]+: 382.1181.
4.2.31 11-(4-Hydroxyphenyl)-1,6,7,8,9,11-hexahydro-10H-pyrazolo[3,4-a]acridin-10-one (6f)
Yellow solid, m.p. 240-242 °C; IR (KBr) (ν, cm-1): 3268, 3150, 1667, 1593, 1479, 1390, 1253,
1197, 1127, 976, 933, 839, 764, 640, 592; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.84 (s, 1H,
NH), 9.68 (s, 1H, NH), 9.06 (s, 1H, OH), 7.91 (s, 1H, ArH), 7.48 (d, J = 8.4 Hz, 1H, ArH), 7.13 (d,
J = 8.4 Hz, 2H, ArH), 6.86 (d, J = 8.8 Hz, 1H, ArH), 6.52 (d, J = 8.4 Hz, 2H, ArH), 5.44 (s, 1H,
CH), 2.68-2.55 (m, 2H, CH2), 2.28-2.21 (m, 2H, CH2), 1.98-1.92 (m, 1H, CH), 1.87-1.83 (m, 1H,
CH); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 193.9, 155.8, 153.5, 139.2, 138.3, 134.5, 134.4,
128.7, 120.1, 119.3, 114.9, 111.8, 108.8, 107.1, 37.3, 34.7, 27.5, 21.5; HRMS (ESI-TOF) m/z
calculated for C20H17N3NaO2: 354.1218, found [M+Na]+: 354.1229.
4.2.32 8,8-Dimethyl-11-phenyl-1,6,7,8,9,11-hexahydro-10H-pyrazolo[3,4-a]acridin-10-one (6g)
Yellow solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3421, 3178, 1610, 1594, 1490, 1395, 1255, 1152,
1030, 930, 853, 797, 696, 612, 538; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.85 (s, 1H, NH),
9.61 (s, 1H, NH), 7.92 (d, J = 0.8 Hz, 1H, ArH), 7.51 (d, J = 8.4 Hz, 1H, ArH), 6.96 (d, J = 1.2 Hz,
1H, ArH), 6.86 (d, J = 8.8 Hz, 1H, ArH), 6.80 (dd, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H, ArH), 6.68 (d, J =
8.4 Hz, 1H, ArH), 5.87 (d, J = 8.4 Hz, 2H, ArH), 5.42 (s, 1H, CH), 2.55 (d, J = 16.8 Hz, 1H, CH),
2.43 (d, J = 16.4 Hz, 1H, CH), 2.23 (d, J = 16.0 Hz, 1H, CH), 2.04 (d, J = 16.0 Hz, 1H, CH), 1.05
(s, 3H, CH3), 0.95 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 193.4, 152.0, 147.4,
139.1, 134.6, 134.5, 128.2, 127.8, 126.2, 120.2, 119.6, 111.8, 107.2, 106.5, 50.7, 35.8, 32.6, 29.7,
27.0; HRMS (ESI-TOF) m/z calculated for C22H21N3NaO: 366.1582, found [M+Na]+: 366.1588.
4.2.33
11-(4-Fluorophenyl)-8,8-dimethyl-1,6,7,8,9,11-hexahydro-10H-pyrazolo[3,4-a]acridin-10-one
(6h)
Yellow solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3428, 3174, 1676, 1496, 1392, 1265, 1120, 1030,
930, 848, 600, 558, 550, 489; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.89 (s, 1H, NH), 9.65 (s,
1H, NH), 7.93 (s, 1H, ArH), 7.52 (d, J = 8.4 Hz, 1H, ArH), 7.38 (dd, J1 = 8.8 Hz, J2 = 5.6 Hz, 2H,
ArH), 6.97 (t, J = 8.8 Hz, 2H, ArH), 6.88 (d, J = 8.4 Hz, 1H, ArH), 5.53 (s, 1H, CH), 2.56 (d, J =
21

ACCEPTED MANUSCRIPT
16.8 Hz 1H, CH), 2.42 (d, J = 16.4 Hz, 1H, CH), 2.23 (d, J = 16.0 Hz, 1H, CH), 2.02 (d, J = 16.0
Hz, 1H, CH), 1.05 (s, 3H, CH3), 0.92 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6) (δ, ppm):
193.4, 162.1, 159.7, 152.0, 143.5, 134.6, 129.5 (d, JCF = 7.9 Hz), 120.0 (d, JCF = 37.9 Hz), 119.8,
115.0, 114.8 (d, JCF = 20.8 Hz), 111.8, 107.1, 106.2, 50.7, 35.1, 32.6, 29.7, 28.3, 27.0; HRMS
(ESI-TOF) m/z calculated for C22H20FN3NaO: 384.1488, found [M+Na]+: 384.1470.
4.2.34
11-(4-Chlorophenyl)-8,8-dimethyl-1,6,7,8,9,11-hexahydro-10H-pyrazolo[3,4-a]acridin-10-one (6i)
Yellow solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3443, 1631, 1489, 1397, 1156, 1080, 1028, 708,
577; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.89 (s, 1H, NH), 9.68 (s, 1H, NH), 7.93 (s, 1H,
ArH), 7.53 (d, J = 8.4 Hz, 1H, ArH), 7.37 (d, J = 8.4 Hz, 2H, ArH), 7.21 (d, J = 8.4 Hz, 2H, ArH),
6.88 (d, J = 8.8 Hz, 1H, ArH), 5.53 (s, 1H, CH), 2.56 (s, J = 16.4 Hz 1H, CH), 2.42 (d, J = 16.4 Hz,
1H, CH), 2.23 (d, J = 16.0 Hz, 1H, CH), 2.02 (d, J = 16.0 Hz, 1H, CH), 1.04 (s, 3H, CH3), 0.91 (s,
3H, CH3); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 193.4, 152.1, 146.2, 139.1, 134.7, 134.6,
130.8, 129. 7, 128.2, 120.2, 112.0, 111.8, 106.9, 105.8, 50. 7, 35.4, 32.6, 29. 7, 27.0; HRMS
(ESI-TOF) m/z calculated for C22H20ClN3NaO: 400.1193, found [M+Na]+: 400.1175.
4.2.35
11-(4-Bromophenyl)-8,8-dimethyl-1,6,7,8,9,11-hexahydro-10H-pyrazolo[3,4-a]acridin-10-one (6j)
Yellow solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3421, 3177, 1680, 1593, 1482, 1450, 1391, 1152,
1
1030, 929, 848, 664, 596; H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.89 (s, 1H, NH), 9.68 (s,
1H, NH), 7.93 (d, J = 0.8 Hz, 1H, ArH), 7.53 (d, J = 8.4 Hz, 1H, ArH), 7.37-7.34 (m, 2H, ArH),
7.33-7.30 (m, 2H, ArH), 6.88 (d, J = 8.4 Hz, 1H, ArH), 5.51 (s, 1H, CH), 2.56 (d, J = 16.8 Hz, 1H,
CH), 2.42 (d, J = 16.8 Hz, 1H, CH), 2.23 (d, J = 16.4 Hz, 1H, CH), 2.02 (d, J = 15.6 Hz, 1H, CH),
1.04 (s, 3H, CH3), 0.91 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 193.4, 152.1,
146.6, 139.1, 134.6, 134.6, 131.1, 130.1, 120.2, 112.0, 119.4, 111.8, 106.8, 105.8, 50.7, 35.5, 32.6,
29.7, 27.0; HRMS (ESI-TOF) m/z calculated for C22H20BrN3NaO: 444.0687, found [M+Na]+:
444.0689.
4.2.36 8,8-Dimethyl-11-(p-tolyl)-1,6,7,8,9,11-hexahydro-10H-pyrazolo[3,4-a]acridin-10-one (6k)
Yellow solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3417, 3174, 1675, 1597, 1494, 1450, 1393, 1149,
1074, 1031, 930, 888, 843, 739, 663, 602; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.84 (s, 1H,
22

ACCEPTED MANUSCRIPT
NH), 9.59 (s, 1H, NH), 7.91 (s, 1H, ArH), 7.50 (d, J = 8.4 Hz, 1H, ArH), 7.27 (d, J = 7.6 Hz, 2H,
ArH), 6.94 (d, J = 7.6 Hz, 2H, ArH), 6.86 (d, J = 8.4 Hz, 1H, ArH), 5.47 (s, 1H, CH), 2.56 (d, J =
16.8 Hz, 1H, CH), 2.42 (d, J = 16.4 Hz, 1H, CH), 2.23 (d, J = 16.0 Hz, 1H, CH), 2.14 (s, 3H, CH3),
2.01 (d, J = 16.0 Hz, 1H, CH), 1.05 (s, 3H, CH3), 0.94 (s, 3H, CH3); 13C NMR (100 MHz,
DMSO-d6) (δ, ppm): 193.4, 151.8, 144.6, 139.1, 135.1, 134.5, 134.4, 128.8, 127.7, 120.2, 119.5,
111.8, 107.3, 106.7, 50.8, 35.4, 32.6, 29.8, 27.0, 21.0; HRMS (ESI-TOF) m/z calculated for
C23H23N3NaO: 380.1739, found [M+Na]+: 380.1750.
4.2.37
11-(4-Methoxyphenyl)-8,8-dimethyl-1,6,7,8,9,11-hexahydro-10H-pyrazolo[3,4-a]acridin-10-one
(6l)
Yellow solid, m.p. >280 °C; IR (KBr) (ν, cm-1): 3171, 1668, 1610, 1592, 1505, 1392, 1303, 1264,
1149, 1031, 931, 839, 742, 654, 594; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.85 (s, 1H, NH),
9.59 (s, 1H, NH), 7.91 (d, J = 1.2 Hz, 1H, ArH), 7.50 (d, J = 8.8 Hz, 1H, ArH), 7.29 (d, J = 8.4 Hz,
2H, ArH), 6.86 (d, J = 8.4 Hz, 1H, ArH), 6.70 (d, J = 8.4 Hz, 2H, ArH), 5.46 (s, 1H, CH), 3.62 (s,
3H, CH3), 2.56 (d, J = 16.4 Hz, 1H, CH), 2.42 (d, J = 16.8 Hz, 1H, CH), 2.23 (d, J = 16.0 Hz, 1H,
CH), 2.02 (d, J = 16.0 Hz, 1H, CH), 1.05 (s, 3H, CH3), 0.94 (s, 3H, CH3); 13C NMR (100 MHz,
DMSO-d6) (δ, ppm): 193.4, 157.8, 151.7, 139.8, 139.1, 134.5, 134.4, 128.8, 120.2, 119.5, 113.6,
111.8, 107.4, 106.9, 55.3, 50.8, 34.9, 32.6, 29.7, 27.0; HRMS (ESI-TOF) m/z calculated for
C23H23N3NaO2: 396.1688, found [M+Na]+: 396.1690.
4.2.38
11-(4-Fluorophenyl)-8,8-dimethyl-3,6,7,8,9,11-hexahydro-10H-imidazo[4,5-a]acridin-10-one(8a)
Yellow solid, m.p. 210-212 °C; IR (KBr) (ν, cm-1): 3436, 1632, 1601, 1506, 1489, 1471, 1387,
1
1308, 1232, 1156, 1028, 596, 535, 484; H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.34 (s, 1H,
NH), 9.54 (s, 1H,NH), 8.06 (s, 1H, ArH), 7.39 (d, J = 8.0 Hz, 1H, ArH), 7.32 (dd, J1 = 7.8 Hz, J2 =
6.0 Hz, 2H, ArH), 6.95 (t, J = 8.9 Hz, 3H, ArH), 5.62 (s, 1H, CH), 2.54 (d, J = 16.4 Hz, 1H, CH),
2.43 (d, J = 16.4 Hz, 1H, CH), 2.22 (d, J = 16.0 Hz, 1H, CH), 2.02 (d, J = 15.6 Hz, 1H, CH), 1.04
(s, 3H, CH3), 0.94 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 193.1, 162.0, 159.6,
152.3, 144.0, 141.8, 131.8, 129.5, 129.4, 114.9, 114.6, 111.7, 106.1, 50.7, 35.3, 32.6, 29.7, 28.3,
27.1; HRMS (ESI-TOF) m/z calculated for C22H20FN3NaO: 384.1488, found [M+Na]+: 384.1495.
23

ACCEPTED MANUSCRIPT
4.2.39
11-(3-Bromophenyl)-8,8-dimethyl-3,6,7,8,9,11-hexahydro-10H-imidazo[4,5-a]acridin-10-one(8b)
Yellow solid, m.p. 207-209 °C; IR (KBr) (ν, cm-1): 3435, 1630, 1536, 1472, 1393, 1260, 1233,
1
1151, 1121, 1026, 800, 671, 592; H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.36 (s, 1H, NH),
9.58 (s, 1H, NH), 8.08 (s, 1H, ArH), 7.53 (s, 1H, ArH), 7.41 (s, 1H, ArH), 7.26 (d, J = 7.6 Hz, 1H,
ArH), 7.21 (d, J = 7.6 Hz, 1H, ArH), 7.10 (t, J = 7.6 Hz, 1H, ArH), 6.94 (d, J = 8.8 Hz, 1H, ArH),
5.57 (s, 1H, CH), 2.55 (d, J = 16.8 Hz, 1H, CH), 2.44 (d, J = 16.4 Hz, 1H, CH), 2.22 (d, J = 16.0
Hz, 1H, CH), 2.03 (d, J = 16.0 Hz, 1H, CH), 1.05 (s, 3H, CH3), 0.94 (s, 3H, CH3); 13C NMR (100
MHz, DMSO-d6) (δ, ppm): 193.1, 157.1, 152.5, 143.4, 142.5, 141.6, 138.8, 130.6, 128.8, 126.8,
121.6, 111.7, 104.9, 50.6, 36.0, 32.6, 29.7, 26.9; HRMS (ESI-TOF) m/z calculated for
C22H20BrN3NaO: 444.0687, found [M+Na]+: 444.0671.
4.2.40 8,8-Dimethyl-11-(p-tolyl)-3,6,7,8,9,11-hexahydro-10H-imidazo[4,5-a]acridin-10-one(8c)
Yellow solid, m.p. 213-215°C; IR (KBr) (ν, cm-1): 3415, 1631, 1537, 1470, 1391, 1262, 1235,
1
1155, 1120, 1028, 809, 675, 594; H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.34 (s, 1H, NH),
9.49 (s, 1H, NH), 8.06 (s, 1H, ArH), 7.36 (d, J = 8.4 Hz, 1H, ArH), 7.20 (d, J = 7.6 Hz, 2H, ArH),
6.92 (d, J = 6.8 Hz, 3H, ArH), 5.54 (s, 1H, CH), 2.54 (d, J = 16.4 Hz, 1H, CH), 2.42 (d, J = 16.4
Hz, 1H, CH), 2.21 (d, J = 16.0 Hz, 1H, CH), 2.14 (s, 3H, CH3), 2.00 (d, J = 16.0 Hz, 1H, CH),
1.05 (s, 3H, CH3), 0.95 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 193.1, 152.1,
144.8, 134.9, 132.2, 128.7, 127.7, 112.0, 106.4, 50.8, 35.6, 32.6, 31.2, 29.8, 27.1, 21.0; HRMS
(ESI-TOF) m/z calculated for C23H23N3NaO: 380.1739, found [M+Na]+: 380.1760.
4.2.41 11-(4-Methoxyphenyl)-8,8-dimethyl-3,6,7,8,9,11-hexahydro-10H-imidazo[4,5-a]
acridin-10-one(8d)
Yellow solid, m.p. 212-214°C; IR (KBr) (ν, cm-1): 3134, 1585, 1508, 1473, 1397, 1282, 1254,
1175, 1121, 1030, 808, 565; 1H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.29 (s, 1H, NH), 9.47 (s,
1H, NH), 8.04 (s, 1H, ArH), 7.35 (s, 1H, ArH), 7.22 (d, J = 8.4 Hz, 2H, ArH), 6.91 (d, J = 8.8 Hz,
1H, ArH), 6.68 (d, J = 8.4 Hz, 2H, ArH), 5.52 (s, 1H, CH), 3.62 (s, 3H, CH3), 2.54 (d, J = 16.8 Hz,
1H, CH), 2.42 (d, J = 16.8 Hz, 1H, CH), 2.21 (d, J = 16.0 Hz, 1H, CH), 2.01 (d, J = 16.0 Hz, 1H,
CH), 1.05 (s, 3H. CH3), 0.95 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 193.1,
157.6, 152.0, 141.7, 140.2, 128.7, 113.5, 111.5, 106.4, 55.3, 50.8, 35.1, 32.6, 29.8, 27.1; HRMS
24

ACCEPTED MANUSCRIPT
(ESI-TOF) m/z calculated for C23H23N3NaO2: 396.1688, found [M+Na]+: 396.1697.
4.2.42 11-(Benzo[d][1,3]dioxol-5-yl)-8,8-dimethyl-3,6,7,8,9,11-hexahydro-10H-imidazo[4,5-a]ac
ridin-10-one(8e)
Yellow solid, m.p. 227-229°C; IR (KBr) (ν, cm-1): 3130, 1622, 1535, 1488, 1401, 1236, 1152,
1
1041, 925, 858, 812, 798, 664, 628, 593; H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.30 (s, 1H,
NH), 9.52 (s, 1H, NH), 8.06 (s, 1H, ArH), 7.38 (s, 1H, ArH), 6.93-6.89 (m, 2H, ArH), 6.74 (d, J =
8.0 Hz, 1H, ArH), 6.66 (d, J = 8.0 Hz, 1H, ArH), 5.86 (d, J = 7.6 Hz, 2H, ArH), 5.46 (s, 1H, CH),
2.53 (d, J = 16.4 Hz, 1H, CH), 2.44 (d, J = 16.4 Hz, 1H, CH), 2.21 (d, J = 16.0 Hz, 1H, CH), 2.03
(d, J = 16.0 Hz, 1H, CH), 1.04 (s, 3H, CH3), 0.96 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6)
(δ, ppm): 193.1, 152.2, 147.1, 145.4, 141.8, 120.6, 111.5, 108.5, 108.0, 106.3, 100.9, 50.8, 35.7,
32.6, 31.2, 29.7, 27.2; HRMS (ESI-TOF) m/z calculated for C23H21N3NaO3: 410.1481, found
[M+Na]+: 410.1488.
Acknowledgment
We are grateful to National Natural Science Foundation of China (NSFC) (No. 51174201,
21571087), the Open Foundation of Jiangsu Key Laboratory of Green Synthetic Chemistry for
Functional Materials (No. K201312), the Major Projects of Natural Science Research in Jiangsu
Province (No. 15KJA150004), the College students' innovative projects in jiangsu province (No.
201610320049Z), the Priority Academic Program Development of Jiangsu Higher Education
Institutions for financial support, and this work was also sponsored by TAPP.
Supplementary Material 1H NMR and 13C NMR spectra for all compounds are available free of
charge via the Internet. Crystallographic data (excluding structure factors) for the structure 4c
reported in this paper has been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication no. CCDC 1567615 and can be obtained free of charge on application
to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44(1223)336033; E-mail:
deposit@ccdc.cam.ac.uk, or via www.ccdc.cam.ac.uk/data_request/cif.
References and notes
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E. F. V., Eds.; Pergamon Press: Oxford, 1996; p 167.
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Bioorg. Med. Chem. Lett. 2008, 18, 3783; b) Tedesco, R.; Shaw, A. N.; Bambal, R.; Chai, D.;
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Concha, N. O.; Darcy, M.G.; Dhanak, D.; Fitch, D. M.; Gates, A.; Gerhardt, W. G.; Halegoua,
D. L.; Han, C.; Hofmann, G. A.; Johnston, V. K.; Kaura, A. C.; Liu, N.; Keenan, R. M.;
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27

ACCEPTED MANUSCRIPT
HO
N
H
N
N
N
F3C
N
O
Cl
O
O
O
N
NO2
O
N
4
N
N
H
N
O
H
H
A (inhibitor of HIV-1
reverse transcriptase)
C (cilostazol)
B (carteolol)
N(CH3)2
N
NO2
H3CO
NH2
H2N
N
Cl
N
O
N
H
H
NO2
E (porflavine)
F (anticancer compound)
D (NMDA antagonist)
Figure 1. Pharmaceuticals containing the dihydroquinolin-2-one and acridine structures.
Scheme 1 Synthesis of 4a under screening conditions.
Table 1. Optimization of reaction conditions for synthesis of 4aa.
Ratio
Entry
Solvent
Temperature/oC
Time (h)
Yield (%)b
(2/SnCl2·H2O)
1
2
THF
EtOH
MeCN
CHCl3
DMF
THF
50
50
50
50
50
60
80
80
80
80
80
80
80
80
1:2
5
5
5
5
5
5
5
5
5
5
6
7
7
56
45
36
32
24
61
75
89
87
88
87
86
55
63
1:2
3
1:2
4
1:2
5
1:2
6
1:2
7
THF
1:2
8
THF
1:3
9
THF
1:4
10
11
12
13
14
THF
1:5
1:3
THF
THF
1:3
EtOH
EtOH
1:3 [Fe-HCl (1mL)]
1:3 [Fe-HCl (1mL)]
10
28