Synthesis of 1H-indazolo[2,1-b]phthalazine-triones catalysed by proline triflate under solvent-free conditions

Article abstract of DOI:10.3184/174751912X13251821462738

An efficient procedure has been developed for the synthesis of 1H-indazolo[2,1-b]phthalazine-triones by the one-pot condensation of cyclohexane-1,3-dione, aromatic aldehydes and phthalhydrazides catalysed by proline triflate under solvent-free conditions.

Full text of DOI:10.3184/174751912X13251821462738

JOURNAL OF CHEMICAL RESEARCH 2012
RESEARCH PAPER 17
JANUARY, 17–20
Synthesis of 1H-indazolo[2,1-b]phthalazine-triones catalysed by proline
triflate under solvent-free conditions
Xiangjun Shi, Jia Li, Weihui Zhong and Jianjun Li*
Key Laboratory of Pharmaceutical Engineering of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of
Technology, Hangzhou 310014, P. R. China
An efficient procedure has been developed for the synthesis of 1H-indazolo[2,1-b]phthalazine-triones by the one-pot
condensation of cyclohexane-1,3-dione, aromatic aldehydes and phthalhydrazides catalysed by proline triflate under
solvent-free conditions. The reaction proceeds in good to excellent yields.
Keywords: proline triflate, one-pot condensation, indazolophthalazine, solvent-free conditions, multi-component reactions
Multicomponent reactions (MCRs) continue to attract
attention because they provide the desired products in a single
operation without the isolation of intermediates.1 As a result
of their high efficiency, they are useful in the synthesis of
heterocyclic compounds.2,3
Heterocyclic compounds possessing a pyrazole ring were
examined because of their vasodilator, and anti-AIDS activity
(Fig. 1).4,5 Heterocycles containing a phthalazine moiety are
widely studied in the pharmaceutical and biochemical fields
(Fig. 2).6 Phthalazine derivatives were found to possess
anti-convulsant,7 cardiotonic,8 vaso-relaxant,6 anti-cancer,9 and
anti-inflammatory activities.10
It is not surprising that many synthetic routes have
been developed for these compounds.11–15 Recently, Bazgir16
has reported the formation of structure of 2H-indazolo
[2,1-b]pthalazine-1,6,11(13H)-triones derivative using pTSA
as a catalyst. Several other routes for the synthesis of 1H-
indazolo[2,1-b]phthalazine-triones have been reported.17–21
Although a variety of catalysts have been introduced for this
cyclo-condensation, many of these methodologies are associ-
ated with one or more disadvantages such as environmentally
unfriendly catalysts, strong acid, and harsh reaction condi-
tions. Hence, it is still necessary to develop new catalysts for
the synthesis of heterocycles possessing a phthalazine ring
fragment and to make better use of a one-pot synthesis strategy
because of the increasing environmental concerns of chemical
research and industry.
Organocatalysis is becoming an increasing well-investigated
area since it avoids the use of metals which can be both expen-
sive and toxic. Ammonium triflate is a new organocatalyst
which has been applied in a variety of reactions where it has
displayed great catalytic activity and efficiency.22–24 The use of
less hazardous solvents or solvent-free catalytic reactions has
been examined in the area of green synthesis.25 In this paper,
which is aimed at developing environmentally friendly
methodologies for the preparation of indazolophthalazine, we
now show that proline triflate26 catalysed three-component
condensation without solvent.
In order to optimise the reaction conditions, we investigated
the reaction of benzaldehydes (1a), cyclohexane-1,3-dione (2),
and phthalhydrazide (3) in various solvents (Table 1). We
found that benzene and toluene were unsuitable for the
reaction (entries 5 and 6). Solvents such as ethanol, methanol,
acetonitrile and DMF, displayed poor activity in the reaction
(entries 1–4). Fortuitously, using proline triflate as catalyst
under solvent-free condition gave much better results com-
pared to the reaction in a solvent (entry 7). Among all the acid
catalyst we used, proline triflate was particularly effective
requiring a short time and giving a high yield (entries, 8–10).
The desired product was not obtained without the use of any
catalyst, even when the reaction time was lengthened to 15 h
(entry 13).
The influence of the amount of catalyst was examined.
As shown in Table 1, 67% yield of 4a was obtained when
5 mol% proline triflate was used, which increased to 92% as
Table 1 Effect of different reaction conditionsa
Entry Catalyst/mol%
Solvent
Temp Time Yieldb
/oC
/h
of 4a/%
Fig. 1 Heterocyclics possessing pyrazole ring own vasodilator,
anti-AIDS activity.
1
2
Proline triflate (10)
Proline triflate (10)
Proline triflate (10)
Proline triflate (10)
Proline triflate (10)
Proline triflate (10)
Proline triflate (10)
PTSA (20)
EtOH
MeOH
MeCN
DMF
Reflux 10.0
Reflux 10.0
Reflux 10.0
30
35
35
50
10
Trace
92
73
63
–
3
4
100
10.0
5
Benzene Reflux 10.0
6
Toluene
100
80
15.0
3.0
7
–
–
–
–
–
–
–
–
8
80
3.0
9
CF3SO3H (10)
80
3.0
10
11
12
13
14
L-proline (20)
80
3.0
Proline triflate (5)
Proline triflate (20)
None
80
3.0
67
90
–
80
3.0
100
20
15.0
10.0
Fig. 2 Phthalazine derivatives are widely applied in the
pharmaceutical and biochemical fields.
Proline triflate (10)
21
a Reaction conditions: benzaldehyde/phthalhydrazide/cyclohex-
ane-1,3-dione= 1.3:1:1.
b Isolated yield based on 1a.
* Correspondent. E-mail: pharmlab@zjut.edu.cn

18 JOURNAL OF CHEMICAL RESEARCH 2012
catalyst loading went up to 10 mol% (entries, 7, 11). Ten mole
percent of proline triflate was sufficient and excess catalyst
did not increase the yield significantly. It was obvious that
temperature was an important factor (entry 14). Furthermore,
the reuse of the catalyst was also examined. The catalyst
can be easily recovered from the reaction mixture simply by
washing with H2O and evaporating the water. The catalyst can
be reused in the reaction five times without significant loss in
catalytic activity (87–90% yield).
Subsequently a series of indazolophthalazine derivatives
4a–j were prepared from various aldehydes following the opti-
mised procedure. As shown in Table 2, the reactions proceed
smoothly to generate products in good yields (87–92%). It was
found that the presence of an electron-donating or an electron-
withdrawing group on the aromatic ring of the aldehydes did
not significantly affect the reaction. However, the bromine
substituted phthalhydrazide 5 gave slightly reduced yields of
products 6a–d. The results indicate that aldehydes possessing
electron-donating substituents afforded higher yields than
aldehydes with electron-withdrawing group (Table 3).
Knoevenagel condensation of aldehyde and cyclohexane-1,3-
dione in the presence of proline triflate. Subsequently, the
Michael-type addition of phthalhydrazide 3 to 9 and afforded
intermediate 10, which was readly transformed into 4 by
cyclo-dehydration.
In summary, we have described an efficient one-pot proce-
dure for the synthesis of indazolophthalazine derivatives
employing proline triflate as a new catalyst. The method offers
several advantages including short reaction times, high conver-
sions, and ease of handling which make it an attractive and
useful addition to the existing methods for the synthesis of het-
erocycles possessing a phthalazine ring.
Experimental
Melting points were recorded on a Buchi R-535 apparatus and are
uncorrected. IR spectra were recorded using KBr pellets on a Nicolet
Aviatar-370 instrument. The NMR spectra were measured with a
Bruker Advance III 500 or Varian Mercury Plus-400 instrument using
CDCl3 as the solvent with TMS as internal standard. Mass spectra
were measured with Thermo Finnigan LCQ-Advantage.
The present method has been extended to the synthesis of
indazolophthalazine derivatives 8 by the condensations of
aldehydes, 1,2-dihydropyridazine-3,6-dione(7) and cyclohex-
ane-1,3-dione in the presence of proline triflate under similar
conditions (Scheme 1). Compound 7 was not as reactive as
phthalhydrazide in this reaction. Hence, the reaction needed
more catalyst and longer times.
Syntheses; general procedure
13-Aryl-3,4-dihydro-1H-indazolo[2,1-b]phthalazine-1,6,11(2H,13H)-
trione derivatives 4a–j. A dry 25-mL flask was charged with cyclo-
hexane-1,3-dione 2 (1 mmol), phthalhydrazide 3 (1 mmol), aldehyde
1 (1.3 mmol). The mixture together with proline triflate (10 mol%)
was stirred at 80 °C for 3–4 h (TLC). After cooling, the reaction mix-
ture was washed with water (10 mL) and the residue recrystallised
from methanol to afford the pure product 4a–j.
13-Aryl-3,4-dihydro-1H-indazolo[2,1-b]phthalazine-1,6,11(2H,13H)-
trione derivatives 6a–d. A dry 25-mL flask was charged with cyclo-
hexane-1,3-dione 2 (1 mmol), bromine substituted phthalhydrazide 5
(1 mmol), aldehyde 1 (1.3 mmol). The mixture together with proline
triflate (10 mol%) was stirred at 80 °C for 3 h (TLC). After cooling,
the reaction mixture was washed with water (10 mL) and the residue
recrystallised from methanol to afford the pure product 6a–d.
13-Aryl-3,4-dihydro-1H-indazolo[2,1-b]phthalazine-1,6,11(2H,13H)-
trione 8. A dry 25-mL flask was charged with cyclohexane-1,3-dione
2 (1 mmol), 1,2-dihydropyridazine-3,6-dione 7 (1 mmol), benzalde-
hyde 1a (1.3 mmol). The mixture together with proline triflate
(20 mol%) was stirred at 80 °C for 5 h (TLC). After cooling, the
reaction mixture was washed with water (10 mL) and the residue
recrystallised from methanol to afford the pure product 8.
From the above results, a possible mechanism is shown in
Scheme 2. First, the intermediates dione 9 was formed by the
Table 2 One-pot synthesis of 4 catalysed by proline triflatea
Entry
1
Ar
Time/h Product Yieldb/%
1
2
1a
1b
1c
1d
1e
1f
C6H5
3.0
3.0
3.0
3.0
4.0
3.0
3.5
3.0
3.0
3.0
4a
4b
4c
4d
4e
4f
92
90
90
94
87
90
89
90
91
92
p-ClC6H4
Spectral data
3
p-CH3OC6H4
p-CH3C6H4
p-O2NC6H4
m-CH3OC6H4
m-BrC6H4
m-FC6H4
13-Phenyl-3,4-dihydro-1H-indazolo[2,1-b]phthalazine-1,6,11(2H,13H)-
4
trione (4a): M.p. 226–229 °C (lit.22 223–225 °C). IR (KBr) νmax: 2954,
5
1
1659, 1624 cm−1. H NMR(400 MHz, CDCl3) δ: 8.28–8.26 (1H, m,
6
7
1g
1h
1i
4g
4h
4i
ArH), 8.11–8.08 (1H, m, ArH), 7.98–7.94 (2H, m, ArH), 7.46–7.44
(2H, m, ArH), 7.32–7.24 (3H, m, ArH), 6.26 (1H, s, CH), 3.49–3.41
(1H, m, CH2), 3.26–3.16 (1H, m, CH2), 2.36–2.33 (2H, m, CH2),
2.15–2.10 (2H, m CH2). 13C NMR (100 MHz, CDCl3) δ: 192.3, 155.3,
153.6, 152.9, 134.7, 134.5, 133.7, 129.0, 128.6, 128.1, 127.9, 127.5,
127.4, 126.7, 118.3, 64.3, 36.4, 24.0, 21.8. MS (ESI): m/z = 367
[M+Na]+.
8
9
o-ClC6H4
3,4-(CH3)2C6H3
10
1j
4j
a Reaction conditions: aldehyde/phthalhydrazide/cyclohexane-
1,3-dione = 1.3:1:1, 10 mol% proline triflate, 80 °C.
b Isolated yield.
13-(4-Chlorophenyl)-3,4-dihydro-1H-indazolo[2,1-b]phthalazine-
1,6,11(2H,13H)-trione (4b): M.p. 285–289 °C (lit.23 272–273 °C).
IR (KBr) νmax: 2947, 1662, 1625 cm−1. H NMR(400 MHz, CDCl3)
1
Table 3 One-pot synthesis of 6 from bromine substitute
phthalhydrazide catalysed by proline triflatea
δ: 8.36–8.34 (1H, m, ArH), 8.27–8.25 (1H, m, ArH), 7.87–7.84 (2H,
m, ArH), 7.38–7.27 (4H, m, ArH), 6.41 (1H, s, CH), 3.58–3.47 (1H,
m, CH2), 3.36–3.30 (1H, m, CH2), 2.48–2.45 (2H, m, CH2), 2.28–2.24
(2H, m, CH2). 13C NMR (100 MHz, CDCl3) δ: 192.4, 156.0, 154.3,
152.5, 134.9, 134.6, 134.5, 133.6, 128.9, 128.5, 128.0, 127.7, 119.1,
64.3, 36.8, 24.4, 22.2. MS (ESI): m/z = 379 [M+1]+.
13-(4-Methoxyphenyl)-3,4-dihydro-1H-indazolo[2,1-b]phthalazine-
1,6,11(2H,13H)-trione (4c): M.p. 260–263 °C (lit.22 242–244 °C).
Entry
1
Ar
Time/h Product Yieldb/%
1
IR (KBr) νmax: 2951, 1658, 1625 cm–1. H NMR (400 MHz, CDCl3)
1
2
3
4
1a
1b
1c
1d
C6H5
p-ClC6H4
p-CH3OC6H4
3,4-(CH3)2C6H3
3.0
3.0
3.0
3.0
6a
6b
6c
6d
85
76
82
80
δ: 8.35–8.33 (1H, m, ArH), 8.28–8.25 (1H, m, ArH), 7.85–7.81 (2H,
m, ArH), 7.36–7.33 (2H, m, ArH), 6.87–6.84 (2H, m, ArH), 6.42 (1H,
s, CH), 3.76 (3H, s, OCH3), 3.60–3.55 (1H, m, CH2), 3.36–3.30 (1H,
m, CH2), 2.49–2.45 (2H, m, CH2), 2.29–2.24 (2H, m, CH2). 13C NMR
(100 MHz, CDCl3) δ: 192.8, 156.4, 154.5, 152.4, 134.8, 133.7, 129.5,
129.3, 128.8, 128.6, 128.2, 128.0, 120.0, 114.4, 64.9, 55.5, 37.3, 24.8,
22.6. MS (ESI): m/z = 375[M+1]+.
a Reaction conditions: aldehyde/phthalhydrazide/ cyclohexane-
1,3-dione= 1.3:1:1, 10 mol% proline triflate, 80 °C.
b Isolated yield.

JOURNAL OF CHEMICAL RESEARCH 2012 19
Scheme 1 One-pot synthesis of 8 from 7.
Scheme 2 Proposed reaction mechanism.
13-p-Tolyl-3,4-dihydro-1H-indazolo[2,1-b]phthalazine-1,6,11(2H,13H)-
129.6, 128.9, 128.8, 128.0, 127.7, 122.7, 118.9, 64.2, 36.8, 24.4, 22.2.
MS (ESI): m/z = 423 [M+H]+. HRMS-ESI: Calcd for C21H16BrN2O3
423.0344; found: 423.0343.
trione (4d): M.p. 238–244 °C (lit.24 not reported). IR (KBr) νmax: 2940,
1
1661, 1626 cm–1. H NMR(400 MHz, CDCl3) δ: 8.36–8.33 (1H, m,
ArH), 8.27–8.25 (1H, m, ArH), 7.85–7.83 (2H, m, ArH), 7.32–7.26
(2H, m, ArH), 7.15–7.13 (2H, m, ArH), 6.42 (1H, s, CH), 3.60–3.53
(1H, m, CH2), 3.37–3.28 (1H, m, CH2), 2.48–2.44 (2H, m, CH2), 2.29
(3H, s, CH3), 2.28–2.22 (2H, m, CH2). 13C NMR (100 MHz, CDCl3) δ:
192.5, 156.0, 154.2, 152.1, 138.5, 134.4, 133.4, 133.3, 129.4, 129.2,
128.9, 127.9, 127.7, 127.1, 119.8, 64.8, 36.9, 24.5, 22.3, 21.2. MS
(ESI): m/z = 359 [M+1]+.
13-(3-Fluorophenyl)-3,4-dihydro-1H-indazolo[2,1-b]phthalazine-
1,6,11(2H,13H)-trione (4h): M.p. 228–232 °C. IR (KBr) νmax: 2954,
1663, 1653, 1622 cm–1. 1H NMR (400 MHz, CDCl3) δ: 8.38–8.36 (1H,
m, ArH), 8.29–8.27 (1H, m, ArH), 7.88–7.86 (2H, m, ArH), 7.34–7.25
(2H, m, ArH), 7.10–6.96 (2H, m, ArH), 6.44 (1H, s, CH), 3.60–3.49
(1H, m, CH2), 3.35–3.30 (1H, m, CH2), 2.52–2.41 (2H, m, CH2),
2.29–2.24 (2H, m, CH2). 13C NMR (100 MHz, CDCl3) δ: 192.3, 156.0,
154.3, 152.5, 138.9, 134.6, 133.6, 130.2, 128.9, 128.0, 127.7, 123.1,
119.1, 115.5, 114.1, 64.3, 36.8, 24.4, 22.2. MS (ESI): m/z = 363
[M+H]+. HRMS-ESI: Calcd for C21H16FN2O3 363.1145; found:
363.1149.
13-(2-Chlorophenyl)-3,4-dihydro-1H-indazolo[2,1-b]phthalazine-
1,6,11(2H,13H)-trione (4i): M.p. 274–280 °C (lit.23 M.p. 250–
252 °C). IR (KBr) νmax: 2955, 1663, 1626 cm–1. 1H NMR (400 MHz,
CDCl3) δ: 8.38–8.34 (1H, m, ArH), 8.31–8.22 (1H, m, ArH),
7.87–7.82 (2H, m, ArH), 7.50–7.48 (1H, m, ArH), 7.32–6.21 (3H, m,
ArH), 6.66 (1H, s, CH), 3.56–3.47 (1H, m, CH2), 3.40–3.32 (1H, m,
CH2), 2.47–2.43 (2H, m, CH2), 2.27–2.21 (2H,m, CH2). 13C NMR
(100 MHz, CDCl3) δ: 192.3, 156.1, 154.1, 153.2, 134.5, 133.5, 132.9,
132.6, 130.8, 130.4, 129.0, 128.7, 128.0, 127.6, 127.1, 64.1, 36.8,
24.4, 22.2. MS (ESI): m/z = 401[M+Na]+.
13-(4-Nitrophenyl)-3,4-dihydro-1H-indazolo[2,1-b]phthalazine-
1,6,11(2H,13H)-trione (4e): M.p. 243–246 °C (lit.22 not reported).
1
IR (KBr) νmax: 2954, 1655, 1615 cm–1. H NMR (400 MHz, CDCl3)
δ: 8.40–8.37 (1H, m, ArH), 8.27–8.26 (1H, m, ArH), 8.24–8.19 (2H,
m, ArH), 7.91–7.87 (2H, m, ArH), 7.63–7.61 (2H, m, ArH), 6.51 (1H,
s, CH), 3.61–3.53 (1H, m, CH2), 3.40–3.32 (1H, m, CH2), 2.49–2.46
(2H, m, CH2), 2.30–2.23 (2H, m, CH2). 13C NMR (100 MHz, CDCl3)
δ: 192.3, 156.0, 154.5, 153.0, 147.9, 143.3, 134.8, 133.9, 128.9, 128.7,
128.2, 128.1, 127.8, 124.0, 118.4, 64.2, 36.8, 24.5, 22.2. MS (ESI):
m/z = 388[M+1]+.
13-(3-Methoxyphenyl)-3,4-dihydro-1H-indazolo[2,1-b]phthalazine-
1,6,11(2H,13H)-trione (4f): M.p. 221–224 °C(lit.23 210–211 °C).
1
IR (KBr) νmax: 2941, 1660, 1625 cm–1. H NMR(400 MHz, CDCl3)
δ: 8.36–8.33 (1H, m, ArH), 8.28–8.25 (1H, m, ArH), 7.85–7.82 (2H,
m, ArH), 7.27–7.23 (1H, m, ArH), 7.02–6.96 (2H, m, ArH), 6.83–6.80
(1H, m, ArH), 6.42 (1H, s, CH), 3.78 (3H, s, OCH3), 3.59–3.51 (1H,
m, CH2), 3.35–3.28 (1H, m, CH2), 2.48–2.44 (2H, m, CH2), 2.27–2.17
(2H, m, CH2). 13C NMR (100 MHz, CDCl3) δ: 192.4, 156.0, 154.2,
152.2, 137.9, 134.4, 133.5, 129.0, 128.9, 127.9, 127.7, 119.6, 119.4,
113.6, 113.2, 64.7, 55.2, 36.9, 24.4, 22.2. MS (ESI): m/z =
375[M+1]+.
13-(3,4-Dimethylphenyl)-3,4-dihydro-1H-indazolo[2,1-b]phthalazine-
1,6,11(2H,13H)-trione (4j): M.p. 241–244 °C. IR (KBr) νmax: 2941,
1
1654, 1622 cm–1. H NMR (400 MHz, CDCl3) δ: 8.36–8.34 (1H, m,
ArH), 8.28–8.25 (1H, m, ArH), 7.86–7.81 (2H, m, ArH), 7.16–7.07
(3H, m, ArH), 6.39 (1H, s, CH), 3.62–3.54 (1H, m, CH2), 3.36–3.28
(1H, m, CH2), 2.48–2.44 (2H, m, CH2), 2.28–2.23 (2H, m, CH2), 2.22
(3H, s, CH3), 2.19 (3H, s, CH3). 13C NMR (100 MHz, CDCl3) δ: 192.8,
156.4, 154.5, 152.3, 137.5, 137.2, 134.7, 134.0, 133.7, 130.3, 129.5,
128.7, 128.2, 124.8, 120.3, 65.2, 37.3, 24.8, 22.6, 20.2, 19.8. MS
(ESI): m/z = 373[M+1]+. HRMS-ESI: Calcd for C23H21N2O3 373.1552;
found: 373.1554.
13-(3-Bromophenyl)-3,4-dihydro-1H-indazolo[2,1-b]phthalazine-
1,6,11(2H,13H)-trione (4g): M.p. 207–211 °C. IR (KBr) νmax: 2955,
1
1662, 1638 cm–1. H NMR (400 MHz, CDCl3) δ: 8.38–8.35 (1H, m,
ArH), 8.28–8.26 (1H, m, ArH), 7.89–7.85 (2H, m, ArH), 7.47–7.40
(3H, m, ArH), 7.26–7.20 (1H, m, ArH), 6.39 (1H, s, CH), 3.61–3.53
(1H, m, CH2), 3.36–3.30 (1H, m, CH2), 2.47(2H, dd, J1 = 6.0Hz,
J2 = 12.8Hz, CH2), 2.29–2.23 (2H, m, CH2). 13C NMR (100 MHz,
CDCl3) δ: 192.4, 155.9, 154.3, 152.6, 138.5, 134.6, 131.7, 130.1,
8-Bromo-13-phenyl-3,4-dihydro-1H-indazolo[2,1-b]phthalazine-
1,6,11(2H,13H)-trione (6a): M.p. 274–278 °C. IR (KBr) νmax: 2944,
1
1661, 1644 cm–1. H NMR (400 MHz, CDCl3) δ: 8.48 (1H, s, ArH),
8.11 (1H, d, J = 8.4Hz, ArH), 7.95 (1H, d, J = 8.4Hz, ArH), 7.41–7.29

20 JOURNAL OF CHEMICAL RESEARCH 2012
(5H, m, ArH), 6.43 (1H, s, CH), 3.58–3.50 (1H, m, CH2), 3.33–3.29
We are grateful to the National Natural Science Foundation of
China (No 20806073) for financial support.
(1H, m, CH2), 2.48–2.46 (2H, m, CH2), 2.29–2.24 (2H, m, CH2). 13
C
NMR (100 MHz, CDCl3) δ: 192.5, 154.7, 153.6, 151.9, 134.5, 133.5,
132.9, 132.6, 130.8, 130.4, 129.0, 128.7, 128.0, 127.6, 127.1, 64.7,
36.9, 24.4, 22.3. MS (ESI): m/z = 423 [M+1]+. HRMS-ESI: Calcd for
C21H15BrN2O3 423.0344; found: 423.0346.
Received 17 October 2011; accepted 21 December 2011
Paper 1100938 doi: 10.3184/174751912X13251821462738
Published online: 31 January 2012
8-Bromo-13-(4-chlorophenyl)-3,4-dihydro-1H-indazolo[2,1-b]
phthalazine-1,6,11(2H,13H)-trione (6b): M.p. 254–258 °C. IR (KBr)
νmax: 2955, 1663, 1650 cm–1. 1H NMR(400 MHz, CDCl3) δ: 8.48 (1H,
s, ArH), 8.11 (1H, d, J = 8.4Hz, ArH), 7.96 (1H, d, J = 7.6Hz, ArH),
7.36–7.30 (4H, m, ArH), 6.39 (1H, s, CH), 3.58–3.50 (1H, m, CH2),
3.33–3.29 (1H, m, CH2), 2.49–2.46 (2H, m, CH2), 2.27–2.24 (2H, m,
CH2). 13C NMR (100 MHz, CDCl3) δ: 192.3, 154.7, 153.8, 152.3,
137.8, 134.7, 134.6, 130.9, 130.3, 129.4, 129.0, 128.6, 127.7, 119.5,
64.5, 36.9, 24.4, 22.2. MS (ESI): m/z = 457 [M+1]+. HRMS-ESI:
Calcd for C21H15BrClN2O3 456.9955; found: 456.9955.
8-Bromo-13-(4-methoxyphenyl)-3,4-dihydro-1H-indazolo[2,1-b]
phthalazine-1,6,11(2H,13H)-trione (6c): M.p. 245–249 °C. IR (KBr)
νmax: 2940, 1658, 1639 cm–1. 1H NMR(400 MHz, CDCl3) δ: 8.48 (1H,
s, ArH), 8.12 (1H, d, J = 8.4Hz, ArH), 7.96–7.93 (1H, m, ArH), 7.34
(2H, d, J = 8.8Hz, ArH), 6.86 (2H, d, J = 8.8Hz, ArH), 6.40 (1H, s,
CH), 3.77 (3H, s, OCH3), 3.58−3.53 (1H, m, CH2), 3.34–3.31 (1H, m,
CH2), 2.50–2.46 (2H, m, CH2), 2.28–2.25(2H, m, CH2). 13C NMR
(100 MHz, CDCl3) δ:192.7, 160.0, 154.9, 152.2, 137.9, 137.0, 134.7,
133.7, 131.0, 130.5, 129.6, 128.7, 128.1, 120.2, 114.3, 65.0, 55.4,
37.1, 24.7, 22.5. MS (ESI): m/z = 453 [M+1]+. HRMS-ESI: Calcd for
C22H18BrN2O4 453.0450; found: 453.0454.
8-Bromo-13-(3,4-dimethylphenyl)-3,4-dihydro-1H-indazolo[2,1-b]
phthalazine-1,6,11(2H,13H)-trione (6d): M.p. 222–225 °C. IR (KBr)
νmax: 2951, 1658, 1643 cm–1. 1H NMR (400 MHz, CDCl3) δ: 8.39 (1H,
s, ArH), 8.19 (1H, d, J = 8.8Hz, ArH), 7.95–7.92 (1H, m, ArH),
7.16–7.07 (3H, m, ArH), 6.37 (1H, s, CH), 3.60–3.49 (1H, m, CH2),
3.35–3.28 (1H, m, CH2), 2.48–2.44 (2H, m, CH2), 2.28–2.26 (2H, m,
CH2), 2.23 (3H, s, CH3), 2.19 (3H, s, CH3). 13C NMR (100 MHz,
CDCl3) δ:192.4, 155.4, 152.8, 151.8, 137.3, 136.9, 133.2, 130.7,
130.4, 129.9, 129.4, 127.9, 124.5, 120.0, 65.1, 36.9, 24.4, 22.2, 19.9,
19.5. MS (ESI): m/z = 451 [M+1]+. HRMS-ESI: Calcd for
C23H20BrN2O3 451.0657; found: 451.0660.
11-Phenyl-3,4-dihydro-1H-pyridazino[1,2-a]indazole-1,6,9(2H, 11H)-
trione (8): M.p. 213–216 °C. IR (KBr) νmax: 2940, 1655, 1643 cm–1.
1H NMR (400 MHz, CDCl3) δ: 7.36–7.26 (5H, m, ArH), 6.91 (2H, s,
CH), 6.29 (1H, s, CH), 3.49–3.40 (1H, m, CH2), 3.28–3.20 (1H, m,
CH2), 2.46–2.43 (2H, m, CH2), 2.25–2.18 (2H, m, CH2). 13C NMR
(100 MHz, CDCl3) δ: 192.3, 154.9, 153.1, 151.7, 136.1, 135.0, 134.8,
128.8, 128.7, 127.1, 120.0, 65.4, 36.9, 23.9, 22.1. MS (EI): m/z (%) =
295 (15) [M+1]+, 217 (100). HRMS-EI: Calcd for C17H15N2O3
295.1083; found: 295.1086.
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