Palladium-Catalyzed Cascade Approach to 12-(Aryl)indolo[1,2- c ]quinazolin-6(5 H)-ones

Article abstract of DOI:10.1055/s-0036-1589158

A straightforward one-pot approach to the synthesis of challenging 12-arylindolo[1,2- c ]quinazolin-6(5 H)-ones is described. Starting from readily available o -(o -aminophenylethynyl)trifluoroacetanilides, palladium-catalyzed aminoarylation of the triple bond with ArI, ArBr, and ArN ₂⁺ BF ₄^- is followed by cyclization of the resulting N -trifluoroacetyl-2-(o -aminophenyl)-3-aryl indole. This sequential reaction provides the title compounds by means of a rare elimination of trifluoromethane.

Full text of DOI:10.1055/s-0036-1589158

SYNTHESIS
0
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1
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, 1133–1140
paper
1133
en
A. Arcadi et al.
Paper
Synthesis
Palladium-Catalyzed Cascade Approach to 12-(Aryl)indolo-
[1,2-c]quinazolin-6(5H)-ones
Antonio Arcadia
-
Sandro Cacchib
H2N
Giancarlo Fabrizib
Francesca Ghirgac
Antonella Goggiamanib
Antonia Iazzetti*b
Fabio Marinelli*a
X
R
R2
R2
Pd(PPh3)4
R1
R1
+
K2CO3
MeCN, 100 °C
R
N
NHCOCF3
R1 = H, Me, CF3; R2 = H, Me
NH
X = Br, 14 examples, 51–96%
X = I, 13 examples, 57–95%
X = N2+, 4 examples, 50–63%
O
R = o-, m-, p- EWG and EDG; H
a Dipartimento di Scienze Fisiche e Chimiche, Università di L’Aquila,
Via Vetoio, 67010 Coppito (AQ), Italy
b Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza,
Università di Roma, P.le A. Moro 5, 00185, Rome, Italy
antonella.goggiamani@uniroma1.it
c Center for Life Nano Science@Sapienza, Istituto Italiano di
Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy
Received: 26.10.2017
Accepted after revision: 30.11.2017
Published online: 02.01.2018
tive elimination sequence. We have also explored its
application to the build-up of various fused indole scaf-
folds.11
DOI: 10.1055/s-0036-1589158; Art ID: ss-2017-t0692-op
In particular, we previously reported that the readily
available [o-(aminophenyl)ethynyl]trifluoroacetanilide (1a)
led to 6-aryl-11H-indolo[3,2-c]quinolines 3 through a two-
step procedure; namely, palladium-catalyzed carbonylative
annulation with aryl iodides to give intermediate 3-acyl-
indoles 2, followed by hydrolysis of the trifluoroacetanilide
group and cyclization (Scheme 1, a).11a Given the impor-
tance of the indoloquinazolinones, we were interested in
extending our methodology to this class of compounds.
Now, we wish to report that, under suitable reaction condi-
tions, 1a affords 12-arylindolo[1,2-c]quinazolin-6(5H)-ones
5 through a simple and efficient sequential process
(Scheme 1, b).
Abstract A straightforward one-pot approach to the synthesis of chal-
lenging 12-arylindolo[1,2-c]quinazolin-6(5H)-ones is described. Start-
ing from readily available o-(o-aminophenylethynyl)trifluoroacetani-
lides, palladium-catalyzed aminoarylation of the triple bond with ArI,
–
ArBr, and ArN2+BF4 is followed by cyclization of the resulting N-trifluoro-
acetyl-2-(o-aminophenyl)-3-aryl indole. This sequential reaction provides
the title compounds by means of a rare elimination of trifluorometh-
ane.
Key words indoles, quinazolinones, palladium, trifluoromethane,
elimination, polycycles
Indole derivatives are one of the most extensively stud-
ied class of heterocyclic compounds,1 because the indole
nucleus is a fundamental constituent of many natural and
synthetic products with biological activity.2 Moreover,
fused indole derivatives display a number of interesting
pharmacological properties. The tetracyclic alkaloid skele-
ton, consisting of a quinazolinone fused to an indole unit, is
found in several natural products including tryptanthrin,3a,b
and ophiuroidine,3c which exhibit antibiotic,4 antiparasitic,5
anticancer,6 and antitubercular activities.7 As such, the in-
doloquinazolinone system still motivates organic chemists
to develop chemically and economically efficient and sus-
tainable methodologies for their preparation.8 Although a
variety of synthetic methods have been developed for the
preparation of natural indoloquinazolinones and their con-
Pd(PPh3)4
K2CO3
ArBr (4) or
ArI (10) or
ArN2+BF4- (11)
H2N
Ar
N
b:
Present work
NH
NHCOCF3
O
5
1a
Pd(PPh3)4
K2CO3
ArI,
CO
O
Ar
Ar
N
geners,3a,9
the
synthesis
of
12-(aryl)indolo[1,2-
K2CO3
c]quinazolin-6(5H)-ones 5 is quite challenging.
N
MeOH, H2O
H
N
Pd-catalyzed cyclization of o-alkynyltrifluoroacetani-
lides with organic electrophiles has been shown to repre-
sent a general methodology for the construction of func-
tionalized indoles,10 through an aminopalladation/reduc-
HN
H
a:
Previous work
COCF3
2
3
Scheme 1 Present and previously reported reactions starting from 1a
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, 1133–1140

1134
A. Arcadi et al.
Paper
Synthesis
Initially, we examined the reaction of the alkynyltriflu-
oroacetanilide 1a with an excess of 4-bromoanisole (4a) us-
ing 5 mol% Pd(PPh3)4 as catalyst and different base/solvent
combinations at 100 °C.12 The reaction proceeded to give
12-(4-methoxyphenyl)indolo[1,2-c]quinazolin-6(5H)-one
(5a), together with variable amounts of 12-unsubstituted
indoloquinazolinone 6. To our knowledge, only compound
5b (with Ph in place of p-MeOC6H4) has been previously
prepared through a complex multistep reaction,13 and other
derivatives are unknown. Therefore, an efficient and simple
strategy to build up indoloquinazolinones 5 is desirable,
and we attempted the optimization of the reaction parame-
ters to address the selective preparation of 5a from 1a (Ta-
ble 1).
fluoro, chloro, cyano, and nitro groups, were tolerated on
the aromatic ring of 4. Good results were also achieved in
the presence of substituents at the ortho-position of ArBr
(entries 4 and 8), whereas the outcome of the palladium-
catalyzed reaction of 1a with 1-bromo-3-(trifluoro-
methyl)benzene 4k was less favorable (entry 11). In this
case, increasing the temperature to 120 °C led to a better re-
sult (entry 12).
Table 2 Scope of the Reaction of 1a with Aryl Bromides 4a
R
Br
Pd(PPh3)4
(0.05 equiv)
1a
+
K2CO3 (2 equiv)
MeCN, 100 °C
N
R
Table 1 Optimization of the Synthesis of 5aa
NH
4 (3 equiv)
O
5
Ar
Pd(PPh3)4
5 mol%
Entry
4/5
R
Time (h)
Yield (%)b of 5
+
1a + ArBr
base
solvent
100 °C
4a
N
N
1
2
a
b
c
d
e
f
4-OMe
H
30
16
26
25
23
24
40
18
42
25
15
15
80
86
83
61
66
62
64
67
73
96
51c
63d
NH
NH
O
5a
O
Ar = p-MeOC6H4
6
3
3-OMe
2-Me
4-F
Entry
Base
Solvent
DMF
Time (h) Yield (%)b,c of 5a (6)
4
5
1
2
3
4
5
6
7
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
Na2CO3
Li2CO3
21
20
30
24
22
24
24
38 (35)
78 (9)
6
4-Cl
MeCN/DMF 1:1
MeCN
7
g
h
i
3-CN
2-CN
3-Ac
4-NO2
3-CF3
3-CF3
80 (11)
68d (25)
65 (30)
12 (59)
5e (10)
8
MeCN
9
MeCN
10
11
12
j
MeCN
k
k
MeCN
a Reaction conditions (0.35 mmol scale): ArBr (3 equiv), base (2 equiv),
Pd(PPh3)4 (0.05 equiv), solvent (2 mL).
b Yield of isolated product.
a Reaction conditions: 1a (0.35 mmol), 4 (1.05 mmol), K2CO3 (0.7 mmol),
Pd(PPh3)4 (0.0175 mmol), MeCN (2 mL), 100 °C under argon atmosphere.
b Isolated yield.
c Figures in parentheses refer to the yield of 6.
d Carried out with ArBr (2 equiv).
c 6 was isolated in 20% yield.
e 1a was recovered in 51% yield.
d Carried out at 120 °C.
The solvent was found to play a key role in controlling
the product selectivity, as were the excess of aryl bromide
and the nature of the base. The use of a mixture of
DMF/MeCN or MeCN instead of DMF improved both yields
and selectivity of the process (Table 1, entries 2 and 3). De-
creasing the excess of 4a to 2 equiv (entry 4) led to a lower
yield. Among the bases tested, a moderate yield of 5a was
obtained with Cs2CO3 (entry 5), whereas using Na2CO3 af-
forded 5a in low yield, with the main product being 6 (en-
try 6). Disappointing results were observed with Li2CO3
(entry 7).
A plausible reaction path that accounts for the forma-
tion of products 5 is shown in Scheme 2.
Ar
Ar
ArX, Pd(0)
base
1a
5
N
N
– CF3H
H2N
CF3
HO
F3C
NH
O
7
8
Scheme 2 Plausible reaction path for the formation of 5
The conditions described in Table 1, entry 3 were then
selected to explore the scope and limitations of the meth-
odology. The reaction of 1a with different aryl bromides
under palladium catalysis proceeded smoothly to give the
target indoloquinazolinones 5a–k in moderate to high yield
(Table 2). Several substituents, including methyl, methoxy,
After the Pd-catalyzed cyclization of 1a, the resulting
N-trifluoroacetylindole 7 affords intermediate 8. Finally,
elimination of trifluoromethane (or trifluoromethyl anion)
from 8 generates quinazolinones 5. This elimination is quite
rare, and there are only some precedents in the literature.14
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, 1133–1140

1135
A. Arcadi et al.
Paper
Synthesis
We also attempted to shed light on the formation of by-
product 6. We have previously reported that 1a undergo a
base-promoted cyclization/transamidation when treated
with Et3N in DMF at 90 °C, affording N-(2-(1H-indol-2-
yl)phenyl)-2,2,2-trifluoroacetamide 9 (Scheme 3, b).15
Therefore, base-promoted cyclization of 1a could also be
involved in the formation of 6. To confirm this hypothesis, 1a
was reacted with K2CO3 in CH3CN at 100 °C (omitting ArBr
and Pd catalyst); quinazolinone 6 was isolated in 30% yield,
and 1a was recovered in 63% yield (Scheme 3, a). Therefore,
the formation of 6 is due, at least in part, to the presence of
the base.16
Table 3 Scope of the Reaction of 1a with Aryl Iodides 10a
R
I
Pd(PPh3)4
(0.05 equiv)
1a
+
K2CO3 (2 equiv)
MeCN, 100 °C
N
R
NH
10 (1.2 equiv)
O
5
Entry
10/5
R
Time (h)
Yield (%)b of 5
1
2
a
b
c
4-OMe
H
26
16
17
48
24
24
22
24
18
24
78
86
80
88
90
90
94
95
80
57
3
3-OMe
4-F
H2N
4
e
f
K2CO3
MeCN, 100 °C
a
5
4-Cl
N
10 h
6
k
l
3-CF3
4-CN
4-COOEt
2-OMe
2-Ac
NH
O
NHCOCF3
7
1a
6 (30%)
8
m
n
o
b
Et3N, DMF
90 °C, 4 h
(ref. 15)
9
10
a Reaction conditions: 1a (0.35 mmol), 10 (0.42 mmol), K2CO3 (0.7 mmol),
Pd(PPh3)4 (0.0175 mmol), MeCN (2 mL), 100 °C under argon atmosphere.
b Isolated yield.
N
H
HN
9 (55%)
then performed. The best results were obtained by treating
the crude reaction mixture, after the Pd-catalyzed cycliza-
tion, with two additional equivalents of K2CO3 in DMF (Ta-
ble 4).
COCF3
Scheme 3 Base-promoted reactions of 1a
It is worth nothing that the different outcomes between
the present reaction and the Pd-catalyzed carbonylative cy-
clization of 1a (Scheme 1), as well as the differences in the
base-promoted cyclizations reported in Scheme 3, demon-
strates that the tendency of intermediates of type 8 to un-
dergo elimination of trifluoromethane (affording quinazoli-
nones) or transamidation is strongly dependent on the
base/solvent/temperature combination, as well as on the
particular structure of the initially formed indole ring. Fur-
ther work is needed to clarify this intriguing aspect.
Table 4 Scope of the Reaction of 1a with Arenediazonium Tetra-
fluoroborates 11a
R
–
N2+BF4
1. Pd(PPh3)4 (0.05 equiv)
K2CO3, MeCN, 100 °C
1a +
2. K2CO3 (2 equiv)
DMF, 100 °C, overnight
N
R
NH
O
11 (2 equiv)
5
We then tested the formation of 12-arylindolo[1,2-
c]quinazolin-6(5H)-ones 5 from aryl iodides 10.17 According
to the higher reactivity of these electrophiles in the oxida-
tive addition step, palladium-catalyzed reaction of 1 with a
near stoichiometric amount of 10 (1.2 equiv) resulted in an
efficient reaction (Table 3).
Furthermore, attempts to set up the use of arene di-
azonium salts 11 as a useful alternative to the aryl halides
showed the feasibility of the reaction.18 However, the reac-
tion of 1a with 2 equiv of 11a under the usual reaction con-
ditions (2 equiv K2CO3 and 5% Pd(PPh3)4 in MeCN at 100 °C
for 10 h) afforded 5a in unsatisfactory yield (41%), together
with 9 (20%), 6 (16%) and other unidentified byproducts. A
preliminary optimization of the reaction parameters was
Entry
11/5
R
Time (h)
Yield (%)b of 5
1
2
3
4
a
4-OMe
H
8
9
7
5
58
50
63
61
b
f
4-Cl
m
4-COOEt
a Reaction conditions: 1a (0.35 mmol), 11 (0.7 mmol), K2CO3 (0.7 mmol),
Pd(PPh3)4 (0.0175 mmol), MeCN (2 mL), 80 °C under argon atmosphere
(step 1); then K2CO3 (0.7 mmol) (step 2) in DMF (2 mL) at 100 °C.
b Isolated yield.
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1136
A. Arcadi et al.
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Synthesis
Finally, we tested an extension of the methodology to
the synthesis of disubstituted indoloquinazolinones 5p–t.
Starting compounds 1b–d were easily obtained from Sono-
gashira coupling of substituted 2-iodotrifluoroacetanilides
with ethynylaniline derivatives.
Target disubstituted products were obtained in satisfac-
tory yields, using either aryl bromides or iodides as source
Ar group (Table 5).
Bruker Avance 400 spectrometer. Splitting patterns are designated as
s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), or br s
(broad singlet). Compounds 5d, 5h, 5p were derivatized as N-methyl
derivatives to obtain suitable NMR data. IR spectra were recorded
with a Jasco FT/IR-430 spectrophotometer. ESI accurate mass mea-
surements were recorded with a Finnigan TSQ Quantum Ultra Mass
spectrometer with accurate mass options instrument (5a–p) and
with an Orbitrap Exactive Mass spectrometer with ESI source (1b, 6).
The following compounds were identified by comparison of their
physical and spectral data with those given in the cited references:
1a11a and 6a.14a Compounds 1b–d were prepared by Sonogashira cou-
pling of 2-ethynylaniline or 2-ethynyl-4-methylaniline with the ap-
propriate 2-iodotrifluoroacetanilide derivative using the same gener-
al procedure previously described for 1a.11a
Table 5 Synthesis of Disubstituted Indoloquinazolinones 5p–ta
R
H2N
4 or 10
Pd(PPh3)4
R2
R1
N-{2-[(2-Aminophenyl)ethynyl]-4-(trifluoromethyl)phenyl}-2,2,2-
trifluoroacetamide (1b)
R2
K2CO3
MeCN
100 °C
R1
N
Yield: 0.669 g (65%); beige powder; mp 140–142 °C.
NH
NHCOCF3
O
IR (KBr): 3354, 2197, 1712, 1596 cm–1
.
5p–t
1b–d
1H NMR (DMSO-d6): δ = 11.47 (br s, 1 H), 8.23 (d, J = 1.6 Hz, 1 H), 7.79
(dd, J1 = 8.4, J2 = 1.6 Hz, 1 H), 7.72 (d, J = 8.4 Hz, 1 H), 7.16 (dd, J1 = 7.6;
J2 = 1.2 Hz, 1 H), 7.12–7.06 (m, 1 H), 6.71 (d, J = 8.0 Hz, 1 H), 6.53 (t, J =
7.6 Hz, 1 H), 5.74 (br s, 2 H).
Entry
1
R1, R2
4 or 10
R
Time (h) Yield (%)b of 5
1
2
3
4
5
1b
1b
1c
1d
1d
CF3, H
CF3, H
H, Me
Me, H
Me, H
4a
4-OMe
H
24
20
48
51
24
5p (52)
5q (69)
5r (66)
5s (78)
5t (83)
4b
13C NMR (DMSO-d6): δ = 155.6 (q, JC–F = 36.8 Hz), 150.6, 138.9, 132.5,
10m
10a
10m
4-COOEt
4-OMe
131.1, 129.9, 128.4 (q, JC–F = 32.3 Hz), 127.6, 125.8, 124.1 (q, JC–F
=
270.8 Hz), 121.5, 116.4 (q, JC–F = 286.8 Hz), 116.1, 114.5, 104.7, 94.9,
89.0.
19F NMR (DMSO-d6): δ = –61.1, –73.9.
HRMS: m/z [M–H]– calcd for C17H9F6N2O: 371.0625; found: 371.0618.
4-COOEt
a Reaction conditions: 1 (0.35 mmol), 4 (1.05 mmol) or 10 (0.42 mmol), K2-
CO3 (0.70 mmol), Pd(PPh3)4 (0.017 mmol), CH3CN (2 mL), 100 °C under ar-
gon atmosphere.
b Isolated yield.
N-{2-[(2-Amino-5-methylphenyl)ethynyl]phenyl}-2,2,2-trifluoro-
acetamide (1c)
Yield: 0.648 g (68%); white powder; mp 141–143 °C.
In conclusion, we have reported here an efficient proto-
col for the synthesis of challenging 12-arylindolo[1,2-
c]quinazolin-6(5H)-ones 5 through a straightforward se-
quential reaction that involves an unusual elimination of
trifluoromethane. Aryl iodides, aryl bromides, and arenedi-
azonium salts can be used as σ-donors. The methodology is
quite versatile and tolerates a variety of useful functional
groups; substituents can also be introduced in the benzenic
ring of both indole and quinazolinone moieties. Further
work is in progress to extend the methodology to other σ-
donors.
IR (KBr): 3445, 2194, 1728, 1586, 1545 cm–1
.
1H NMR (CDCl3): δ = 8.88 (br s, 1 H), 8.39 (d, J = 8.4 Hz, 1 H), 7.57 (dd,
J1 = 7.6 Hz, J2= 1.2 Hz, 1 H), 7.46–7.40 (m, 1 H), 7.24 (dt, J1 = 7.6 Hz, J2 =
0.8 Hz, 1 H), 7.18 (s, 1 H), 7.05 (dd, J1 = 8.4 Hz, J2 = 1.6 Hz, 1 H), 6.70 (d,
J = 8.4 Hz), 4.15 (br s, 2 H), 2.28 (s, 3 H).
13C NMR (CDCl3): δ = 154.5 (q, JC–F = 37.2 Hz), 145.7, 135.8, 132.2,
131.8, 131.7, 129.7, 127.6, 125.6, 119.8, 115.7 (q, JC–F = 289.0 Hz),
115.0, 113.9, 106.3, 95.0, 87.8, 20.3.
19F NMR (CDCl3): δ = –75.6.
HRMS: m/z [M
+
H]+ calcd for C17H14F3N2O: 319.1053; found:
319.1046.
N-{2-[(2-Aminophenyl)ethynyl]-4-methylphenyl}-2,2,2-trifluoro-
acetamide (1d)
All of the reagents, catalysts, and solvents are commercially available
and were used as purchased, without further purification. 2-(2-
Aminophenyl)trifluoroacetanilides 1 were prepared through Sono-
gashira cross-coupling of 2-iodotrifluoroacetanilides with 2-ethy-
nylanilines according to previous reports.19 Starting materials were
purified on axially compressed columns, packed with SiO2 25–40 μm,
connected to a preparative pump for solvent delivery and to a refrac-
tive index detector, and eluting with n-hexane/EtOAc mixtures. Reac-
tion products were purified by flash chromatography using SiO2 as
stationary phase, eluting with n-hexane/EtOAc or hexane/EtO-
Ac/MeOH or CHCl3/CH2Cl2 mixtures, depending on the solubility.
Melting points are uncorrected. 1H NMR (400.13 MHz), 13CNMR
(100.6 MHz), and 19F NMR (376.5 MHz) spectra were recorded with a
Yield: 0.715 g (75%); white powder; mp 137–139 °C.
IR (KBr): 3338, 2200, 1710, 1545 cm–1
.
1H NMR (DMSO-d6): δ = 11.16 (br s, 1 H), 7.57 (s, 1 H), 7.35 (d, J =
8.4 Hz, 1 H), 7.27 (d, J = 8.0 Hz, 1 H), 7.18 (d, J = 7.2 Hz, 1 H), 7.10 (t, J =
8.0 Hz, 1 H), 6.73 (d, J = 8.4 Hz, 1 H), 6.55 (t, J = 7.2 Hz, 1 H), 5.57 (br s,
2 H), 2.35 (s, 3 H).
13C NMR (DMSO-d6): δ = 155.70 (q, JC–F = 36.5 Hz), 150.2, 137.6, 133.1,
132.9, 132.2, 130.6, 130.0, 126.9, 120.5, 116.6 (q, JC–F = 284.2 Hz),
116.2, 114.4, 105.5, 92.3, 90.5, 20.8.
19F NMR (CDCl3): δ = –75.6.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, 1133–1140

1137
A. Arcadi et al.
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Synthesis
HRMS: m/z [M
+
H]+ calcd for C17H14F3N2O: 319.1053; found:
IR (KBr): 3376, 2999, 2930, 1702 cm–1
.
319.1045.
1H NMR (DMSO-d6): δ = 11. 41 (br s, 1 H), 8.65 (d, J = 8.4 Hz, 1 H),
7.56–7.46 (m, 2 H), 7.44–7.31 (m, 4 H), 7.28 (d, J = 8.0 Hz, 1 H), 7.13–
7.06 (m, 3 H), 6.97 (t, J = 7.9 Hz, 1 H), 3.77 (3 H).
Synthesis of 12-(Aryl)indolo[1,2-c]quinazolin-6(5H)-ones 5 from
ArBr; Typical Procedure
13C NMR (DMSO-d6): δ = 159.8, 147.1, 134.9, 134.7, 132.3, 130.4
(overlapping), 129.2, 128.4, 123.7, 123.4, 122.4, 118.5, 115.6, 115.5,
114.6, 113.8, 113.7, 55.2.
Preparation of 12-(4-Methoxyphenyl)indolo[1,2-c]quinazolin-
6(5H)-one (5a) from 1a and 1-Bromo-4-methoxybenzene (4a)
HRMS: m/z [M + H]+ calcd for C22H17N2O2: 341.1286; found: 341.1287.
In a 50 mL Carousel Tube Reactor (Radely Discovery Technology) con-
taining a magnetic stirring bar 2-(2-aminophenyl)ethynyl trifluoro-
acetanilide (1a; 106.5 mg, 0.350 mmol) was dissolved at r.t. with an-
hydrous MeCN (1.0 mL). Then, Pd(PPh3)4 (20.2 mg, 0.018 mmol), 1-
bromo-4-methoxybenzene (4a; 196.0 mg, 1.050 mmol), K2CO3 (96.7
mg, 0.7 mmol), and MeCN (1.0 mL) were added. The mixture was
stirred for 30 h at 100 °C under argon. After this time, the reaction
mixture was cooled to r.t., diluted with EtOAc, and washed with wa-
ter. The organic extract was dried over Na2SO4 and concentrated un-
der reduced pressure. The residue was purified by flash chromatogra-
phy (silica gel; n-hexane/EtOAc 80:20 v/v; CHCl3/CH2Cl2 75:25 v/v as
eluent) to afford 12-(4-methoxyphenyl)indolo[1,2-c]quinazolin-
6(5H)-one 5a.
12-(o-Tolyl)indolo[1,2-c]quinazolin-6(5H)-one (5d)
Purified with n-hexane/EtOAc (85:15 v/v) as eluent.
Yield: 69.3 mg from ArBr (61%); white powder; mp 330–332 °C.
IR (KBr): 3364, 3058, 3000, 1700, 1593, 1513, 1488, 1460 cm–1
.
1H NMR (DMSO-d6; as N-methyl derivative): δ = 8.69 (d, J = 8.2 Hz,
1 H), 7.55–7.38 (m, 6 H), 7.38–7.32 (m, 2 H), 7.24–7.15 (m, 2 H), 7.08–
7.01 (m, 1 H), 3.71 (s, 3 H), 2.03 (s, 3 H).
13C NMR (DMSO-d6; as N-methyl derivative): δ = 147.8, 137.7, 136.2,
133.4, 133.2, 131.11, 131.09, 129.9, 129.0, 127.9, 127.2, 124.29,
124.28, 123.5, 123.3, 119.0, 116.3, 115.7, 115.6, 113.9, 30.8, 19.9.
HRMS: m/z [M + H]+ calcd for C23H19N2O: 339.1493; found: 339.1492.
Yield: 95 mg (80%); pale-yellow powder; mp 290–292 °C.
IR (KBr): 3375, 3204, 3147, 2990, 1702, 1605, 1516 cm–1
.
12-(4-Fluorophenyl)indolo[1,2-c]quinazolin-6(5H)-one (5e)
Purified with n-hexane/EtOAc (85:15 v/v) as eluent.
1H NMR (DMSO-d6): δ = 11.42 (br s, 1 H), 8.65 (d, J = 8.1 Hz, 1 H),
7.52–7.31 (m, 7 H), 7.27 (d, J = 7.5 Hz, 1 H), 7.17 (d, J = 8.6 Hz, 2 H),
7.01–6.95 (m, 1 H), 3.88 (s, 3 H).
13C NMR (DMSO-d6): δ = 159.4, 147.6, 135.2, 132.8, 131.9, 131.2,
129.6, 128.9, 125.8, 124.14, 124.09, 123.7, 122.9, 119.0, 116.1, 116.0,
115.2, 115.0, 114.5, 55.6.
Yield: 75.8 mg from ArBr (66%); 101.1 mg from ArI (88%); pale-yellow
powder; mp 290–292 °C.
IR (KBr): 3382, 1703, 1592, 1510, 1486 cm–1
.
1H NMR (DMSO-d6): δ = 11.43 (br s, 1 H), 8.62 (d, J = 8.2 Hz, 1 H),
7.62–7.56 (m, 2 H), 7.49–7.30 (m, 7 H), 7.24 (d, J = 7.6 Hz, 1 H), 7.02–
6.96 (m, 1 H).
HRMS: m/z [M + H]+ calcd for C22H17N2O2: 341.1286; found: 341.1285.
13C NMR (DMSO-d6): δ = 162.4 (d, JC–F = 244.8 Hz), 147.5, 135.3, 132.9
(d, JC–F = 8.6 Hz), 132.8, 130.9, 130.31, 130.28, 129.8, 129.2, 124.25,
124.22, 123.7, 122.9, 118.8, 116.7 (d, JC–F = 21.4 Hz), 116.1, 114.2,
114.1.
Synthesis of 12-(Aryl)indolo[1,2-c]quinazolin-6(5H)-ones 5 from
ArI: Typical Procedure
Preparation 5a from 1a and 1-Iodo-4-methoxybenzene (10a)
This procedure was similar to that of the reaction of 1a with 1-bro-
mo-4-methoxybenzene (4a), the only differences being the amount
of 10a (98 mg, 0.420 mmol) and reaction time (26 h).
19F NMR (DMSO-d6): δ = –113.9.
HRMS: m/z [M
+
H]+ calcd for C21H14FN2O: 329.1083; found:
329.1085.
Yield: 93.0 mg (78%).
12-(4-Chlorophenyl)indolo[1,2-c]quinazolin-6(5H)-one (5f)
Purified with n-hexane/EtOAc (85:15 v/v) as eluent.
12-Phenylindolo[1,2-c]quinazolin-6(5H)-one (5b)
Purified with n-hexane/EtOAc (85:15) as eluent.
Yield: 74.8 mg (62%) from ArBr; 108.7 mg from ArI (90%); white pow-
der; mp 287–289 °C.
Yield: 93.4 mg from ArBr (86%); 93.2 mg from ArI (86%); white pow-
der; mp 274–276 °C (Lit.13 277–279 °C).
IR (KBr): 3440, 1714, 1483, 1450 cm–1
.
IR (KBr): 3447, 1693, 1482, 1451, 1410 cm–1
.
1H NMR (DMSO-d6): δ = 11.50 (br s, 1 H), 8.66 (d, J = 8.2 Hz, 1 H), 7.68
(dt, J1 = 8.4 Hz, J2 = 2.0 Hz, 2 H), 7.69–7.56 (m, 2 H), 7.46–7.33 (m,
5 H), 7.28 (d, J = 7.4 Hz, 1 H), 7.04–7.00 (m, 1 H).
1H NMR (DMSO-d6): δ = 11.40 (br s, 1 H), 8.62 (d, J = 8.2 Hz, 1 H),
7.63–7.46 (m, 5 H), 7.43–7.21 (m, 6 H), 6.94–6.87 (m, 1 H).
13C NMR (DMSO-d6): δ = 147.6, 135.2, 134.0, 132.9, 130.9, 130.7,
129.74, 129.69, 128.9, 128.5, 124.20, 124.16, 123.7, 122.8, 118.9,
116.13, 116.09, 115.2, 114.3.
13C NMR (DMSO-d6): δ = 147.5, 135.3, 133.2, 133.0, 132.9, 132.7,
130.7, 129.9 (overlapping), 129.2, 124.32, 124.28, 123.7, 123.0, 118.7,
116.2 (overlapping), 114.1, 113.8.
HRMS: m/z [M + H]+ calcd for C21H15N2O: 311.1180; found: 311.1179.
HRMS: m/z [M +
H]+ calcd for C21H14ClN2O: 345.0788; found:
345.0789.
12-(3-Methoxyphenyl)indolo[1,2-c]quinazolin-6(5H)-one 5c
3-(6-Oxo-5,6-dihydroindolo[1,2-c]quinazolin-12-yl)benzonitrile
(5g)
Purified with n-hexane/EtOAc (85:15 v/v), CHCl3/CH2Cl2 (75:25 v/v)
as eluent.
Purified with n-hexane/EtOAc (75:25), n-hexane/EtOAc/MeOH
(70:20:10) as eluent.
Yield: 98.9 mg from ArBr (83%); 95.3 from ArI (80%); pale-yellow
powder; mp 215–217 °C.
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Synthesis
Yield: 75.1 mg (64%) from ArBr; pale-yellow powder; mp 278–280 °C.
IR (KBr): 3376, 2229, 1701, 1606, 1482, 1452 cm–1
1H NMR (DMSO-d6): δ = 11.53 (br s, 1 H), 8.66 (d, J = 8.1 Hz, 1 H),
8.08–8.00 (m, 2 H), 7.92 (d, J = 7.8 Hz, 1 H), 7.83 (t, J = 7.7 Hz, 1 H),
7.48–7.34 (m, 5 H), 7.30 (t, J = 8.1 Hz, 1 H), 7.01 (t, J = 7.6 Hz, 1 H).
Yield: 67.5 mg (51%) from ArBr; 119.2 mg (90%) from ArI; white pow-
der; mp 254–256 °C.
.
IR (KBr): 3419, 1697, 1481, 1452 cm–1
.
1H NMR (DMSO-d6): δ = 11.47 (br s, 1 H), 8.64 (d, J = 8.2 Hz, 1 H),
7.92–7.78 (m, 4 H), 7.44–7.23 (m, 6 H), 6.94 (t, J =7.3 Hz, 1 H).
13C NMR (DMSO-d6): δ = 147.5, 136.0, 135.6, 135.4, 134.3, 132.9,
132.4, 131.1, 130.5, 130.0, 129.6, 124.3, 124.39, 123.7, 123.1, 119.1,
118.6, 116.3, 116.2, 113.9, 112.98, 112.96.
13C NMR (DMSO-d6): δ = 147.5, 135.5, 135.4, 135.1, 132.9, 131.0,
130.520 (q, JC–F = 31.4 Hz), 130.519, 130.0, 129.6, 127.3 (q, JC–F
=
3.4 Hz), 125.3 (q, JC–F = 3.1 Hz), 124.6 (q, JC–F = 272.7 Hz), 124.4 (over-
lapping), 123.5, 122.9, 118.5, 116.3, 116.2, 114.0, 113.4.
19F NMR (DMSO-d6): δ = –61.0.
HRMS: m/z [M + H]+ calcd for C22H14N3O: 336.1131; found: 336.1131.
HRMS: m/z [M
+
H]+ calcd for C22H14F3N2O: 379.1048; found:
2-(6-Oxo-5,6-dihydroindolo[1,2-c]quinazolin-12-yl)benzonitrile
(5h)
379.1053.
Purified with n-hexane/EtOAc (75:25), n-hexane/EtOAc/MeOH
(70:20:10) as eluent.
4-(6-Oxo-5,6-dihydroindolo[1,2-c]quinazolin-12-yl)benzonitrile
(5l)
Yield: 78.6 mg (67%) from ArBr; pale-yellow powder; mp 305–307 °C.
Purified with n-hexane/EtOAc (75:25), n-hexane/EtOAc/MeOH
(70:20:10) as eluent.
IR (KBr): 3364, 2221, 1694, 1479, 1450 cm–1
.
1H NMR (CDCl3; as N-methyl derivative): δ = 8.80 (d, J = 8.4 Hz, 1 H),
7.91 (d, J = 7.6 Hz, 1 H), 7.80 (t, J = 7.6 Hz, 1 H), 7.63 (m, 2 H), 7.48–
7.34 (m, 3 H), 7.32–7.23 (m, 3 H), 6.99–6.96 (m, 1 H), 3.77 (s, 3 H).
Yield: 110.4 mg (94%) from ArI; yellow powder; mp 262–264 °C.
IR (KBr): 3378, 2228, 1702, 1603, 1485, 1451 cm–1
.
13C NMR (CDCl3; as N-methyl derivative): δ = 147.9, 138.6, 136.2,
133.9, 133.5, 133.4, 132.2, 130.3, 129.5, 129.0, 128.6, 124.5, 124.2,
124.0, 123.0, 118.2, 117.7, 116.6, 115.3, 114.7, 114.6, 111.0, 30.5.
1H NMR (DMSO-d6): δ = 11.56 (br s, 1 H), 8.67 (d, J = 8.4 Hz, 1 H), 8.09
(d, J = 8.4 Hz, 2 H), 7.80 (d, J = 8.0 Hz, 2 H), 7.46–7.37 (m, 5 H), 7.30 (d,
J = 8.4 Hz, 1 H), 7.04–7.00 (m, 1 H).
HRMS: m/z [M + H]+ calcd for C22H14N3O: 336.1131; found: 336.1131.
13C NMR (DMSO-d6): δ = 147.4, 139.5, 135.4, 133.6, 132.96, 131.94,
130.2, 130.1, 129.5, 124.42, 124.39, 123.8, 123.1, 119.3, 118.5, 116.2
(overlapping), 113.8, 113.4, 111.2.
12-(3-Acetylphenyl)indolo[1,2-c]quinazolin-6(5H)-one (5i)
HRMS: m/z [M + H]+ calcd for C22H14N3O: 336.1131; found: 336.1131.
Purified with n-hexane/EtOAc (75:30), n-hexane/EtOAc/MeOH
(70:20:10) as eluent.
Ethyl 4-(6-Oxo-5,6-dihydroindolo[1,2-c]quinazolin-12-yl)benzo-
ate (5m)
Yield: 90.0 mg (73%) from ArBr; white powder; mp 262–264 °C.
IR (KBr): 3371, 3208, 3149, 1699, 1604, 1560 cm–1
.
Purified with n-hexane/EtOAc (70:30), CHCl3/CH2Cl2 (75:25) as elu-
ent.
1H NMR (DMSO-d6): δ = 11.49 (br s, 1 H), 8.66 (d, J = 8.2 Hz, 1 H),
8.13–8.10 (m, 2 H), 7.82 (dt, J1 = 7.6 Hz, J2 = 1.4 Hz, 1 H), 7.75 (t, J =
8.2 Hz, 1 H), 7.44–7.31 (m, 5 H), 7.27 (d, J = 7.8 Hz, 1 H), 6.97–6.93 (m,
1 H), 2.62 (s, 3 H).
Yield: 127.1 mg (95%) from ArI; white powder; mp 292–294 °C.
IR (KBr): 3374, 3080, 2997, 2930, 1704, 1565, 1511 cm–1
.
13C NMR (DMSO-d6): δ = 198.3, 147.6, 138.2, 135.5, 135.3, 134.6,
132.9, 130.7, 130.4, 130.3, 129.9, 129.3, 128.4, 124.4, 124.3, 123.6,
123.0, 118.7, 116.2, 114.2, 114.1 (overlapping), 27.4.
1H NMR (DMSO-d6): δ = 11.48 (br s, 1 H), 8.64 (d, J = 8.3 Hz, 1 H), 8.15
(d, J = 8.1 Hz, 2 H), 7.69 (d, J = 8.1 Hz, 2 H), 7.43–7.31 (m, 5 H), 7.26 (d,
J = 8 Hz, 1 H), 6.95 (t, J = 7.9 Hz, 1 H), 4.36 (q, J = 7.2 Hz, 2 H), 1.35 (t,
J = 7.2 Hz, 3 H).
13C NMR (DMSO-d6): δ = 166.0, 147.5, 139.3, 135.3, 132.9, 131.2,
130.5, 130.4, 129.9, 129.8, 129.3, 125.0, 124.4, 124.3, 123.0, 118.7,
116.20, 116.23, 114.02, 113.95, 61.3, 14.7.
HRMS: m/z [M + H]+ calcd for C23H17N2O2: 353.1286; found: 353.1285.
12-(4-Nitrophenyl)indolo[1,2-c]quinazolin-6(5H)-one (5j)
Purified with n-hexane/EtOAc (75:25), n-hexane/EtOAc/MeOH
(60:30:10) as eluent.
HRMS: m/z [M + H]+ calcd for C24H19N2O3: 383.1391; found: 383.1390.
Yield: 119.4 mg (96%) from ArBr; yellow powder; mp 330–332 °C.
12-(2-Methoxyphenyl)indolo[1,2-c]quinazolin-6(5H)-one (5n)
Purified with n-hexane/EtOAc 80:20, CHCl3/CH2Cl2 75:25 as eluent.
Yield: 93.7 mg (80%) from ArI; white powder; mp 215–217 °C.
IR (KBr): 3455, 1702, 1515, 1482, 1452 cm–1
.
1H NMR (DMSO-d6): δ = 11.60 (br s, 1 H), 8.68 (d, J = 8.2 Hz, 1 H), 8.46
(d, J = 8.6 Hz, 2 H), 7.89 (d, J = 8.6 Hz, 2 H), 7.40–7.34 (m, 5 H), 7.30 (d,
J = 8.0 Hz, 1 H), 7.00 (t, J = 7.7 Hz, 1 H).
13C NMR (DMSO-d6): δ = 147.5, 147.1, 141.6, 135.5, 133.0, 132.3,
130.2, 130.1, 129.8, 124.9, 124.51, 124.50, 123.9, 123.1, 118.5, 116.3
(overlapping), 113.7, 113.0.
IR (KBr): 3418, 2927, 1706, 1485, 1450 cm–1
1H NMR (DMSO-d6): δ = 11.43 (br s, 1 H), 8.65 (d, J = 8.2 Hz, 1 H),
.
7.58–7.52 (m, 1 H), 7.43–7.224 (m, 8 H), 7.17 (dt, J1 = 7.6 Hz, J2
0.7 Hz, 1 H), 6.99–6.93 (m, 1 H), 3.64 (s, 3 H).
=
HRMS: m/z [M + H]+ calcd for C21H14N3O3: 356.1026; found: 356.1030.
13C NMR (DMSO-d6): δ = 157.9, 147.6, 135.6, 132.8, 131.0, 130.4,
129.6, 129.4, 123.97, 123.96, 123.87, 122.9, 122.2, 121.5, 119.2, 116.0,
115.8, 114.7, 112.4, 111.3, 55.8.
12-(3-(Trifluoromethyl)phenyl)indolo[1,2-c]quinazolin-6(5H)-one
(5k)
HRMS: m/z [M + H]+ calcd for C22H17N2O2: 341.1286; found: 341.1285.
Purified with n-hexane/EtOAc (80:20) as eluent.
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12-(2-Acetylphenyl)indolo[1,2-]quinazolin-6(5H)-one (5o)
Purified with n-hexane/EtOAc/MeOH (65:25:10), as eluent.
Yield: 98.6 mg (57%) from ArI; pale-yellow powder; mp 275–277 °C.
1H NMR (DMSO-d6): δ = 11.43 (br s, 1 H), 8.66 (d, J = 8.1 Hz, 1 H), 8.18
(d, J = 8.1 Hz, 2 H), 7.72 (d, J = 8.1 Hz, 2 H), 7.45–7.31 (m, 3 H), 7.24 (s,
1 H), 7.23–7.16 (m, 3 H), 4.39 (q, J = 7.1 Hz, 2 H), 2.06 (s, 3 H), 1.38 (t,
J = 8.1 Hz, 3 H).
13C NMR (DMSO-d6): δ = 166.0, 147.5, 139.3, 133.2, 133.0, 131.8,
131.3 (overlapping), 130.9, 130.39, 130.37, 129.8, 129.3, 124.3, 123.8,
118.7, 116.2, 116.1, 113.9, 113.8, 61.4, 21.1, 14.7.
IR (KBr): 3212, 3155, 2926, 1691, 1610, 1592, 1494, 1477 cm–1
1H NMR (DMSO-d6): δ = 11.49 (br s, 1 H), 8.65 (d, J = 8.0 Hz, 1 H), 7.95
(dd, J1 = 7.6 Hz, J2= 1.1 Hz, 1 H), 7.78–7.66 (m, 2 H), 7.52 (dd, J1
.
=
7.6 Hz, J2 = 1.0 Hz, 1 H), 7.44–7.32 (m, 4 H), 7.16 (d, J = 7.8 Hz, 1 H),
7.12 (d, J = 7.8 Hz, 1 H), 6.97–6.91 (m, 1 H), 2.10 (s, 3 H).
13C NMR (DMSO-d6): δ = 201.5, 147.6, 141.1, 135.3, 132.8, 132.7,
132.6, 132.2, 131.0, 129.7, 129.6, 129.3, 129.2, 124.3, 124.2, 123.7,
123.0, 118.7, 116.12, 116.08, 114.2, 113.9, 29.6.
HRMS: m/z [M + H]+ calcd for C25H21N2O3: 397.1549; found:
397.1547.
12-(4-Methoxyphenyl)-10-methylindolo[1,2-c]quinazolin-6(5H)-
one (5s)
HRMS: m/z [M + H]+ calcd for C23H17N2O2: 353.1287; found: 353.1285.
Purified with n-hexane/EtOAc (75:25), CH2Cl2/CHCl3 (75:25) as elu-
ent.
12-(4-Methoxyphenyl)-10-(trifluoromethyl)indolo[1,2-
Yield: 96.7 mg (78%) from ArI; white powder; mp 330–332 °C.
IR (KBr): 3364, 3058, 3000, 1700, 1593, 1513, 1488, 1460 cm–1
1H NMR (DMSO-d6): δ = 11.39 (br s, 1 H), 8.50 (d, J = 8.4 Hz, 1 H),
7.49–7.42 (m, 3 H), 7.36–7.32 (m, 1 H), 7.27–7.20 (m, 2 H), 7.17 (d, J =
8.7 Hz, 2 H), 7.12 (s, 1 H), 7.00–6.93 (m, 1 H), 3.88 (s, 3 H), 2.40 (s,
3 H).
c]quinazolin-6(5H)-one (5p)
.
Purified with n-hexane/EtOAc (75:30), CH2Cl2/CHCl3 (75:25) as elu-
ent.
Yield: 70.3 mg (52%) from ArBr; pale-brown powder; mp 272–274 °C.
IR (KBr): 3080, 2929, 1704, 1596, 1492 cm–1
.
1H NMR (DMSO-d6; as N-methyl derivative): δ = 8.83 (d, J = 8.7 Hz,
1 H), 7.71 (dd, J1 = 8.8 Hz, J1 = 1.3 Hz, 1 H),7.59 (d, J = 7.8 Hz, 1 H), 7.54
(s, 1 H), 7.52–7.42 (m, 4 H), 7.18 (d, J = 8.7 Hz, 2 H), 7.11–7.06 (m,
1 H), 3.87 (s, 3 H), 3.68 (s, 3 H).
13C NMR (DMSO-d6; as N-methyl derivative): δ = 159.7, 147.6, 136.4,
134.7, 131.9, 131.0, 130.5, 130.0, 125.2 (q, JC–F = 272.8 Hz), 124.82,
124.83 (q, JC–F = 31.4 Hz), 124.2, 123.3, 120.5 (q, JC–F = 3.3 Hz), 117.2,
116.0, 115.5, 115.1, 114.7, 55.7, 31.0.
13C NMR (DMSO-d6): δ = 159.4, 147.6, 135.2, 133.2, 131.9, 131.5,
131.1, 129.4, 128.9, 125.9, 125.6, 123.6, 122.8, 118.6, 116.0, 115.8,
115.2, 114.7, 114.5, 55.6, 21.6.
HRMS: m/z [M + H]+ calcd for C23H19N2O2: 355.1438; found: 355.1441.
Ethyl 4-(10-Methyl-6-oxo-5,6-dihydroindolo[1,2-c]quinazolin-12-
yl)benzoate (5t)
Purified with n-hexane/EtOAc (70:30), n-hexane/EtOAc/MeOH
(70:20:10) as eluent.
19F NMR (DMSO-d6; as N-methyl derivative): δ = –59.3.
HRMS: m/z [M + H]+ as N-methyl derivative calcd for C24H18 F3N2O2:
Yield: 111.1 mg (83%) from ArI; pale-yellow powder; mp 307–309 °C.
423.1312; found: 423.1315.
IR (KBr): 3378, 2228, 1702, 1603, 1485, 1451 cm–1
.
1H NMR (DMSO-d6): δ = 11.44 (br s, 1 H), 8.48 (d, J = 8.4 Hz, 1 H), 8.14
(d, J = 8.1 Hz, 2 H), 7.66 (d, J = 8.1 Hz, 2 H), 7.37–7.30 (m, 2 H), 7.26–
7.17 (m, 2 H), 7.11 (s, 1 H), 6.93 (t, J = 7.6 Hz, 1 H), 4.35 (q, J = 7.1, 2 H),
2.35 (s, 3 H), 1.34 (t, J = 7.1 Hz, 3 H).
13C NMR (DMSO-d6): δ = 166.0, 147.4, 139.4, 135.3, 133.5, 131.25,
131.23, 130.6, 130.5, 129.83, 129.78, 129.3, 125.8, 123.7, 122.9, 118.3,
116.2, 115.9, 114.0, 113.8, 61.3, 21.6, 14.7.
12-Phenyl-10-(trifluoromethyl)indolo[1,2-c]quinazolin-6(5H)-
one (5q)
Purified with n-hexane/EtOAc (75:30) as eluent.
Yield: 87.4 mg (69%) from ArBr; pale-yellow powder; mp 330–332 °C.
IR (KBr): 3678, 1712, 1618, 1440, 1408 cm–1
.
1H NMR (DMSO-d6): δ = 11.67 (br s, 1 H), 8.81 (d, J = 8.6 Hz, 1 H), 7.73
(dd, J1 = 8.8 Hz, J1 = 1.4 Hz, 1 H), 7.68–7.54 (m, 7 H), 7.46–7.37 (m,
2 H), 7.29 (d, J = 7.6 Hz, 1 H), 7.02–6.96 (m, 1 H).
HRMS: m/z [M + H]+ calcd for C25H21N2O3: 397.1551; found: 397.1547.
13C NMR (DMSO-d6): δ = 147.3, 135.4, 134.9 (overlapping), 134.4,
133.1, 131.1, 130.7, 130.6, 130.4, 130.0, 125.2 (q, JC–F = 272.1 Hz),
124.9 (q, JC–F = 31.5 Hz), 124.0, 123.1, 120.3 (q, JC–F = 4.2 Hz), 117.0,
116.3, 115.7 (q, JC–F = 4.2 Hz), 115.0, 113.9.
Acknowledgment
We gratefully acknowledge the University of l’Aquila and the Sapienza,
University of Rome, for financial support.
19F NMR (DMSO-d6): δ = –59.5.
HRMS: m/z [M–H]– calcd for C22H12F3N2O: 377.0903; found:
377.0907.
Supporting Information
Supporting information for this article is available online at
Ethyl 4-(2-Methyl-6-oxo-5,6-dihydroindolo[1,2-c]quinazolin-12-
yl)benzoate (5r)
https://doi.org/10.1055/s-0036-1589158.
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f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
Purified with n-hexane/EtOAc (75:25), n-hexane/EtOAc/MeOH
(70:20:10) as eluent.
References
Yield: 91.6 mg (66%) from ArI; white powder; mp 276–278 °C.
IR (KBr): 3854, 2924, 1700, 1606, 1513, 1497, 1455 cm–1
.
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