Palladium-Catalyzed C12-Selective Direct Arylation of [1,2- c ]Quinazolin-6(5 H)-ones

Article abstract of DOI:10.1055/s-0037-1610711

A straightforward approach to the synthesis of the challenging 12-arylindolo[1,2- c ]quinazolin-6(5 H)-ones through the palladium-catalyzed direct arylation of N -benzyl and NH-free [1,2- c ]quinazolin-6(5 H)-ones with aryl halides is described.

Full text of DOI:10.1055/s-0037-1610711

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–H
paper
A
en
A. Arcadi et al.
Paper
Synthesis
Palladium-Catalyzed C12-Selective Direct Arylation of [1,2-c]
Quinazolin-6(5H)-ones
Antonio Arcadia
Sandro Cacchib
Giancarlo Fabrizib
Andrea Fochettib
Francesca Ghirgac
Antonella Goggiamani*b
R
R2
R2
X
R1
R1
Pd(OAc)2
DavePhos
+
N
N
TBACl, CsOAc
DMA, 120 °C
R
NH
NH
O
O
Antonia Iazzetti*b
Fabio Marinellia
0
0
0
0-0
0
0
2-
7
7
9
2-7
7
4
X
R1 = H, Me; R2 = H, Me
X = Br, Cl, I; 22 examples, 10–93%
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
antonia.iazzetti@uniroma1.it
c Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia,
Viale Regina Elena 291, 00161 Rome, Italy
Received: 05.03.2019
Accepted after revision: 13.04.2019
Published online: 07.05.2019
Pd(PPh3)4
K2CO3
ArBr
H2N
Ar
ArI or
Y
Y
DOI: 10.1055/s-0037-1610711; Art ID: ss-2019-t0151-op
–
ArN2+BF4
Y
+
previous work
N
N
Abstract A straightforward approach to the synthesis of the challeng-
ing 12-arylindolo[1,2-c]quinazolin-6(5H)-ones through the palladium-
catalyzed direct arylation of N-benzyl and NH-free [1,2-c]quinazolin-
6(5H)-ones with aryl halides is described.
NHCOCF3
NH
NH
O
O
1
4
2
– CF3H
Ar
H N
Ar
2
Key words indoles, quinazolinones, palladium, arylation, polycycles
Y
Y
N
N
The quinazolinone nucleus is a key constituent of many
natural products and represents a versatile building block
for structurally diverse alkaloids and pharmaceuticals.1
More specifically, the quinazolinones fused to an indole
unit, and their synthetic congeners have been relevant tar-
gets due to their structural architectures and promising
bioactivities. Indoloquinazolinones alkaloids exhibit antibi-
otic,2 antiparasitic,3 anticancer,4 and antitubercular activi-
ties.5 Recently, as part of our ongoing efforts in developing
more sustainable methodologies of heterocycles, we fo-
cused on the synthesis of the challenging 12-arylindo-
lo[1,2-c]quinazolin-6(5H)-ones through a straightforward
one-pot approach involving the palladium-catalyzed ami-
noarylation of the triple bond of readily available o-[(o-
aminophenyl)ethynyl]trifluoroacetanilides 1 with ArI, ArBr,
NH
CF3
O
HO
CF3
[I]
[II]
Scheme 1 Previously reported approach to 12-arylindolo[1,2-
c]quinazolin-6(5H)-ones 4
quinazolinone derivatives 2 were isolated as side product of
the reaction.
A competitive base- or palladium-promoted cyclization
of 1 has been supposed to be involved in the formation of
type 2 products. To overcome this drawback, we envisaged
to employ compounds 2 as alternative starting materials for
the preparation of the desired compounds 4 through their
palladium-catalyzed C12-selective direct arylation (Scheme
2), a topic that has received continuous attention and wit-
nessed significant progress during the past decades.8 In par-
ticular, transition-metal-catalyzed C–H bond activation has
emerged as a powerful method in the field of organic syn-
thesis. Although, since the seminal paper by Ohta and co-
workers reporting the C2-arylation of several heteroaro-
matics, the palladium-catalyzed so-called direct arylation
+
–
and ArN2 BF4 , followed by cyclization of the resulting 2-(o-
aminophenyl)-3-aryl-N-trifluoroacetylindole intermediate
[I].6 Then, the sequential process provided the title com-
pounds 4 by means of a fairly rare elimination of trifluoro-
methane from the intermediate [II] (Scheme 1).7 However,
variable amounts (10–20%) of 12-unsubstituted indolo-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H

B
A. Arcadi et al.
Paper
Synthesis
of heteroaryl derivatives proved to be an extremely reliable
method for the synthesis of a wide variety of arylated het-
erocycles, the selective arylation of [1,2-c]quinazolin-
6(5H)-ones has not been explored so far.9 Herein, we report
on the regioselectivity and reactivity of N-benzyl and NH-
free [1,2-c]quinazolin-6(5H)-ones in the presence of palla-
dium complexes. The scope of the direct arylation with a
variety of aryl halides was also examined.
Table 1 Optimization of the Synthesis of 4aaa
OMe
X
[Pd](L)2 (5 mol%)
N
ligand (10 mol%)
N
+
N
O
solvent, base
additive, 120 °C
N
OMe
O
Ar
Y
Y
2a
3a X = Br
3'a X = I
4aa
[Pd]
N
N
ArX 3
N
Entry Solvent/base
Pd/ligand/additive (equiv)
Pd(PPh3)4
X
Yield (%)b,c
of 4aa
N
O
O
R
R
2
4
R = Bz (2a); H (2b)
Y = H (2a, 2b); 2-Me (2c);
10-Me (2d)
1
1,4-dioxane
/K2CO3
Br
–
2
3
toluene/K2CO3 Pd(OAc)2/t-Bu3PHBF4/Me3CO2H (3) Br
10 (10)
– (–)
Scheme 2 Palladium-catalyzed C12-selective direct arylation of [1,2-
c]quinazolin-6(5H)-ones 3
toluene/CsOAc Pd(OAc)2/t-Bu3PHBF4/–
Br
Br
Br
Br
Br
4
DMA/K2CO3
DMA/CsOAc
DMA/CsOAc
DMA/CsOAc
DMA/CsOAc
DMA/CsOAc
DMA/CsOAc
DMA/CsOAcd
DMA/CsOAc
DMA/KOAc
DMA/CsOAc
DMA/CsOAc
DMA/CsOAc
DMA/CsOAc
DMA/Cs2CO3
DMA/CsOAc
Pd(OAc)2/–/–
23 (52)
34 (55)
59 (30)
25
Initially, we explored the reaction of the N-substituted
5-benzylindolo[1,2-c]quinazolin-(5H)-one (2a) with an ex-
cess of 4-bromoanisole (3a) using 5 mol% of the palladium
catalyst and different base/solvent/additive combinations
at 120 °C. The results are gathered in Table 1. When 1,4-di-
oxane or toluene was used as the solvent, the reaction was
disappointing with K2CO3 and CsOAc in the presence of
Pd(PPh3)4 or Pd(OAc)2/t-Bu3PHBF4 as the catalytic system
with and without Me3CO2H as the additive (Table 1, entries
1–3). DMA proved to be the best-tested solvent in both bas-
es. In the presence of Pd(OAc)2 as the catalyst under ligand-
less conditions10 and K2CO3 as the base, the regioselective
arylation at C-12 occurred after prolonged reaction time,
but in low yield (entry 4). A little better result was observed
with the same palladium catalyst in DMA in the presence of
CsOAc as the base and a stoichiometric amount of TBACl,
which was supposed to give beneficial effect by stabilizing
the Pd(0) species (entry 5).11 Further improvement was ob-
tained by the addition of 2 equivalents of i-Pr2NH to facili-
tate both the reduction of Pd(II) and the subsequent oxida-
tive addition of the aryl bromide 3a to Pd(0) (entry 6).
However, Pd2(dba)3 resulted as a less effective catalyst un-
der these latter conditions (entry 7). When a set of combi-
nation of Pd(OAc)2 with phosphine ligands was screened
(Figure 1), DavePhos A proved to play a critical role in the
success of this arylation reaction. Indeed, the formation of
4aa occurred in 79% yield by using the Pd(OAc)2/DavePhos
5
Pd(OAc)2/–/TBACl (1)
6
Pd(OAc)2/–/TBACl (1), i-Pr2NH (2)
Pd2dba3/TBACl (1), i-Pr2NH (2)
7
8
Pd(OAc)2/A/TBACl (1), i-Pr2NH (2) Br
66 (20)
79 (16)
64 (28)
37 (50)
42 (41)
68 (25)
39 (51)
56 (27)
52 (38)
56 (43)
– (51)
9
Pd(OAc)2/A/TBACl (1)
Pd(OAc)2/A/TBACl (3)
Pd(OAc)2/A/TBACl (1)
Pd(OAc)2/A/TBABr (1)
Pd(OAc)2/A/TBACl (1)
Pd(OAc)2/A/–
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
I
10
11
12
13
14
15
16
17
18
19
Pd(OAc)2/B/TBACl (1)
Pd(OAc)2/C/TBACl (1)
Pd(OAc)2/D/TBACl (1)
Pd(OAc)2/D/TBACl (1)
Pd(OAc)2/A/TBACl (1)
63 (30)
a Reactions were carried out at 120 °C on a 0.308 mmol scale, using 3 equiv
of 3, 2 equiv of base, 0.10 equiv of ligand, and 0.05 equiv of Pd in 3 mL of
solvent under argon atmosphere for 24–48 h.
b Yields are given for isolated products.
c Numbers in parentheses refer to the recovered 2a.
d Reaction temperature: 130 °C
combination in the presence of 1 equivalent of TBACl,
whereas under the presence of both TBACl and i-Pr2NH the
product was isolated in a lower yield (entries 8, 9). Increas-
ing the amount of TBACl to 3 equivalents under the pres-
ence of the same catalytic system gave a lower yield of 4aa
as well as increasing the temperature to 130 °C (entries 10,
11). Worse results were observed by changing TBACl to
TBABr (entry 12) and CsOAc to KOAc (entry 13). In the ab-
sence of any additive, the product 4aa was isolated in only
39% yield (entry 14). Other bulky monodentate ligands B, C,
and D (Figure 1) proved to be less effective for this coupling
(entries 15–17) and the key role of the feature of the base is
P(Cy)2
P(Cy)2
P(Cy)2
P(Cy)2
OMe
Me2N
i-PrO
Oi-Pr
Me
MeO
DavePhos
RuPhos
MePhos
SPhos
A
C
B
D
Figure 1 Buchwald ligands employed in screening reactions
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H

C
A. Arcadi et al.
Paper
Synthesis
clearly highlighted by comparison of the results observed in
entries 17 versus 18 of Table 1. When the direct arylation of
2a was carried out under the best reaction conditions with
4-iodoanisole (3′a) as aryl donor, lower yield was observed
(entry 9 vs 19).
high yields (Table 2). Several substituents, including me-
thoxy, carboxyethyl, methyl, chloro, cyano, formyl, and ni-
tro groups, were tolerated on the aromatic ring of 3. Higher
yields were observed in the presence of electron-withdraw-
ing substituents on the para-position of the aromatic ring
of bromides. However, aryl bromides with meta-electron-
donating substituents gave the target compounds 4 in satis-
factory to good yields. In the presence of the 3-OMe group,
an increased yield on the formation of the corresponding
product 4bc was observed by increasing the amount of the
The deprotection of 4a was found to proceed smoothly
in the presence of AlCl3 in anisole at 60 °C (Scheme 3).12
OMe
-
OMe
-
Table 2 Scope of the Reaction of 2 with Aryl Halides 3a
AlCl3 (3 equiv)
anisole, 60 °C, 24 h
N
N
X
N
R1
Pd(OAc)2 (0.05 equiv)
R2
N
O
O
DavePhos A (0.10 equiv)
H
+
N
4a
DMA, CsOAc (2 equiv)
TBACl (1 equiv), 120 °C
4ba (80%)
R3
R3
NH
O
Scheme 3 Deprotection of 4a
3
X = Br
2
R1
3' X = I
R2
3'' X = Cl
Interestingly, the direct arylation of the unprotected in-
dolo[1,2-c]quinazolin-6(5H)-one (2b) can also occur in sat-
isfactory yield under the best reaction conditions of entry 9
of Table 1. A comparison of the results observed in the reac-
tion of 2a,b with the aryl bromides 3a,b is shown in the fol-
lowing Scheme 4.
N
NH
4
O
Entry
R1
R2
Ar–X, R3
3a, 4-OMe
Time (h)
4 Yield (%)b
1
2
H
H
48
48
6
4ba (36)
4ba (30)
4bb (78)
4bc (72)
4bc (88)c
4bd (75)
4be (41)
4bf (93)
4bg (50)
4bh (76)
4bi (48)
4bj (84)
4bk (86)
4ca (66)
4cc (56)
4ch (62)
4cj (78)
4df (65)
4dh (60)
4bl′′ (67)
4bd (50)
4bf (48)
4bc (10)
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
Me
H
H
H
H
3′′a, 4-OMe
3b, 4-CO2Et
3c, 3-OMe
3c, 3-OMe
3d, 4-CN
3e, 4-Me
3f, 4-CHO
3g, 3-Cl
OMe
3
H
4
H
24
27
18
72
20
48
48
48
48
24
48
72
48
48
30
72
48
48
48
48
Br
Pd(OAc)2 (0.05 equiv)
5
H
DavePhos (0.10 equiv)
+
N
DMA, CsOAc (2 equiv)
6
H
N
TBACl (1 equiv), 120 °C
N
R
OMe
N
7
H
O
O
R
8
H
2a,b
3a
4aa (79%, 48 h)
4ba (36%, 48 h)
9
H
10
11
12
13
14
15
16
17
18
19
20
21
22
23
H
3h, H
CO2Et
H
3i, 2-CN
H
3j, 3-Me
Br
Pd(OAc)2 (0.05 equiv)
DavePhos (0.10 equiv)
H
3k, 3-NO2
3b, 4-CO2Et
3c, 3-OMe
3h, H
+
N
Me
Me
Me
Me
H
DMA, CsOAc (2 equiv)
TBACl (1 equiv), 120 °C
N
N
R
CO2Et
N
O
O
R
2a,b
3b
4ab (96%, 3 h)
4bb (78%, 6 h)
3j, 3-Me
Scheme 4 Comparative arylation of the N-protected and -unprotected
indolo[1,2-c]quinazolin-6(5H)-ones 2a,b
3f, 4-CHO
3h, H
H
H
3′′l, 4-COMe
3′′d, 4-CN
3′′f, 4-CHO
3′′c, 3-OMe
Then, these conditions were selected for exploring the
scope and limitations of the direct arylation of the unpro-
tected indolo[1,2-c]quinazolin-6(5H)-ones 2 with aryl bro-
mides. The reaction of indolo[1,2-c]quinazolin-6(5H)-ones
2b–d with different aryl bromides 3a–k in the presence of
Pd(OAc)2/DavePhos catalytic system, TBACl as an additive,
and CsOAc as the base in DMA at 120 °C proceeded to give
the target NH-free indoloquinazolinones 4 in moderate to
H
H
H
a Reactions were carried out with 0.427 mmol of 2, 1.281 mmol of 3, 0.854
mmol of CsOAc, 0.427 mmol of TBACl, 0.043 mmol of DavePhos A, and
0.021 mmol of Pd(OAc)2 in DMA (4 mL) at 120 °C under argon atmosphere.
b Isolated yield.
c TBACl: 0.93 mmol.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H

D
A. Arcadi et al.
Paper
Synthesis
TBACl to 3 equivalents (Table 2, entry 5). The ortho-substit-
uents on aryl halides generally have an important influence
on the yield of the arylation due to their steric and/or coor-
dination properties. Moderate yield was achieved in the
presence of nitrile group at the ortho-position of ArBr (en-
try 11), while with more bulky substituents such as me-
thoxy and acetyl groups the CH arylation does not work.
The use of aryl chlorides 3′′ as a useful alternative to
aryl bromides has been briefly investigated. Moderate
yields were observed in the presence of electron-withdraw-
ing substituents on the para-position of the aromatic ring
of chlorides (Table 2, entries 20–22). However, less reactive
aryl chloride gave the target compound 4 in unsatisfactory
yield (entry 23). Further work is in progress to improve
these results.
In conclusion, we have reported here a complementary
protocol for the synthesis of challenging 12-arylindolo[1,2-
c]quinazolin-6(5H)-ones 4 through a direct palladium-cata-
lyzed arylation of both N-protected and NH-free indo-
lo[1,2-c]quinazolin-6(5H)-ones 2 with aryl bromides, io-
dides, The methodology is quite versatile and tolerates a va-
riety of useful functional groups. Substituents can be
introduced also in the benzene ring of both indole and
quinazolinone moieties. Further work is in progress to ex-
tend the methodology to other -donors.
Then the mixture was cooled to r.t. and concentrated under reduced
pressure. The crude was dissolved in DMSO (20 mL) and K2CO3 (0.908
g, 6.572 mmol) was added. The mixture was stirred at 100 °C for 24 h,
cooled to r.t., diluted with CH2Cl2 (200 mL), washed with brine (50
mL), dried (Na2SO4), and concentrated under reduced pressure. The
residue was purified by flash chromatography (silica gel, n-hexane–
EtOAc, 80:20 v/v) to afford 2b; yield: 0.654 g (85%); white powder;
mp 276–278 °C (Lit.7 mp 280 °C); Rf = 0.2 (n-hexane–EtOAc 60:40).
1H NMR (400.13 MHz, DMSO-d6):  = 11.37 (br s, 1 H), 8.60–8.52 (m, 1
H), 8.53 (dd, J1 = 8.0 Hz, J2 = 0.9 Hz, 1 H), 7.78–7.72 (m, 1 H), 7.48–4.41
(m, 1 H), 7.40–7.33 (m, 3 H), 7.31–7.22 (m, 2 H).
13C NMR (100.6 MHz, DMSO-d6):  = 147.6 (q), 134.7 (q), 134.6 (q),
133.8 (q), 130.1 (q), 129.9 (CH), 124.1 (CH), 123.9 (CH), 123.4 (over-
lapping, CH), 120.7 (CH), 115.9 (CH), 115.8 (CH), 114.1 (q), 98.7 (CH).
5-Benzylindolo[1,2-c]quinazolin-6(5H)-one (2a)
Yield: 0.527 g (95%); beige powder; mp 190–192 °C; Rf = 0.2 (n-hex-
ane–EtOAc 80:20).
IR (KBr): 2920, 2850, 1681, 1471, 1383 cm–1
.
1H NMR (400.13 MHz, CDCl3):  = 8.72–8.60 (m, 1 H), 7.88 (dd, J1 = 7.8
Hz, J2 = 1.3 Hz, 1 H), 7.67–7.60 (m, 1 H), 7.35–7.09 (m, 9 H), 7.05 (d, J =
8.3 Hz, 1 H), 7.02 (s, 1 H), 5.47 (s, 2 H).
13C NMR (100.6 MHz, CDCl3):  = 148.4 (q), 136.3 (q), 134.9 (q), 134.5
(q), 133.2 (q), 130.0 (q), 129.2 (CH), 128.9 (CH), 127.5 (CH), 126.5
(CH), 123.90 (CH), 123.87 (CH), 123.6 (CH), 123.2 (CH), 120.1 (CH),
116.5 (CH), 115.6 (q), 115.3 (CH), 98.4 (CH), 46.8 (CH2).
HRMS: m/z [M + Na]+ calcd for C22H16N2ONa: 347.1155; found:
347.1162.
Melting points are uncorrected. All of the reagents, catalysts, and sol-
vents are commercially available and were used as purchased, with-
out further purification. Indolo[1,2-c]quinazolin-6(5H)-ones 2a–c
were obtained by cyclization of the corresponding o-[(o-aminophe-
nyl)ethynyl]trifluoroacetanilides 1a–c with PdCl2(MeCN)2 followed by
cyclization on the crude (DMSO, K2CO3, 110 °C).13 The o-[(o-amino-
phenyl)ethynyl]trifluoroacetanilides 1a–c were prepared via a Sono-
gashira cross-coupling of 2-iodotrifluoroacetanilides with 2-ethy-
nylanilines according to the literature.6,14 Starting materials were pu-
rified on axially compressed columns, packed with SiO2 25–40 m,
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. 1H
NMR (400.13 MHz), 13C NMR (100.6 MHz), and 19F NMR (376.5 MHz)
spectra were recorded on a Bruker Avance 400 spectrometer. Stan-
dard abbreviations are used to denote the splitting patterns. Com-
pound 4be was derivatized as the N-methyl derivative for obtaining
suitable NMR data. IR spectra were recorded on a Jasco FT/IR-430
spectrophotometer. ESI accurate mass measurements were recorded
using an Orbitrap Exactive mass spectrometer with ESI source. The
following compounds were identified by comparison of their physical
and spectral data with those given in the cited references: 1a–c,6,15
2b,7 4ba–c,d,h, 4ca.6
2-Methylindolo[1,2-c]quinazolin-6(5H)-one (2c)
Yield: 0.611 g (98%); beige powder; mp 265–268 °C; Rf = 0.2 (n-hex-
ane–EtOAc 80:20).
IR (KBr): 3398, 2919, 1556, 1643, 1384 cm–1
.
1H NMR (400.13 MHz, DMSO-d6):  = 11.29 (br s, 1 H), 8.60–8.52 (m, 1
H), 7.92 (s, 1 H), 7.78–7.71 (m, 1 H), 7.40–7.31 (m, 3 H), 7.26 (dd, J1 =
8.2 Hz, J2 = 1.4 Hz, 1 H), 7.17 (d, J = 8.2 Hz, 1 H), 2.39 (s, 3 H).
13C NMR (100.6 MHz, DMSO-d6):  = 147.6 (q), 134.6 (q), 133.8 (q),
132.6 (q), 132.5 (q), 130.9 (CH), 130.1 (q), 123.9 (CH), 123.8 (CH),
123.3 (CH), 120.6 (CH), 115.9 (CH), 115.7 (CH), 113.9 (q), 98.4 (CH),
21.0 (CH3).
HRMS: m/z [M – H]– calcd for C16H11N2O: 247.0877; found: 247.0876.
10-Methylindolo[1,2-c]quinazolin-6(5H)-one (2d)
Yield: 0.504 g (80%); beige powder; mp 281–282 °C; Rf = 0.2 (n-hex-
ane–EtOAc 80:20).
IR (KBr): 3390, 2919, 2854, 1703, 1644, 1383, 1402 cm–1
1H NMR (400.13 MHz, DMSO-d6):  = 11.33 (br s, 1 H), 8.42 (d, J = 8.4
Hz, 1 H), 8.08 (dd, J1 = 7.9 Hz, J2 = 1.0 Hz, 1 H), 7.53 (s, 1 H), 7.45–7.40
(m, 1 H), 7.31–7.16 (m, 4 H) 2.46 (s, 3 H).
13C NMR (100.6 MHz, DMSO-d6):  = 147.9 (q), 134.7 (q), 134.6 (q),
132.9 (q), 132.1 (q), 130.4 (q), 129.8 (CH), 124.9 (CH), 124.1 (CH),
123.4 (CH), 120.3 (CH), 115.8 (CH), 115.6 (CH), 114.1 (q), 98.4 (CH),
21.7 (CH3).
.
Sequential Preparation of Indolo[1,2-c]quinazolin-6(5H)-ones 2;
Indolo[1,2-c]quinazolin-6(5H)-one (2b); Typical Procedure
HRMS m/z [M – H]– calcd for C16H11N2O: 247.0877; found: 247.0876.
To a stirred solution of PdCl2(MeCN)2 (42.6 mg, 0.164 mmol) in MeCN
(10 mL) was added o-[(o-aminophenyl)ethynyl]trifluoroacetanilide
(1a; 1.0 g, 3.286 mmol) and the mixture was stirred at 80 °C for 24 h.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H

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12-Arylindolo[1,2-c]quinazolin-6(5H)-ones 4; Ethyl 4-(6-Oxo-5,6-
dihydroindolo[1,2-c]quinazolin-12-yl)benzoate (4bb); Typical Pro-
cedure
12-(4-Methoxyphenyl)indolo[1,2-c]quinazolin-6(5H)-one (4ba)
Yield: 0.052 g (36%); pale yellow powder; mp 290–292 °C (Lit.6 mp
290–292 °C); Rf = 0.2 (n-hexane–EtOAc 75:25).
In a 50 mL Carousel Tube Reactor (Radely Discovery Technology) con-
taining a magnetic stirring bar, Pd(OAc)2 (4.8 mg, 0.021 mmol) and
DavePhos A (16.8 mg, 0.043 mmol) were dissolved in anhyd DMA (1.0
mL) at r.t. Then, indolo[1,2-c]quinazolin-6(5H)-one (2b; 0.100 g,
0.427 mmol), 1-bromo-4-carbethoxybenzene (3b; 0.293 g, 1.281
mmol), TBACl (0.118 g, 0.427 mmol), CsOAc (0.164 g, 0.854 mmol),
and DMA (3 mL) were added. The reaction mixture was stirred for 6 h
at 120 °C under argon. After this time, the mixture was cooled to r.t.,
diluted with EtOAc (200 mL), and washed with H2O (50 mL). The or-
ganic extract was dried (Na2SO4) and concentrated under reduced
pressure. The residue was purified by flash chromatography (silica
gel, n-hexane–EtOAc 80:20 v/v; CHCl3–CH2Cl2 75:25 v/v) to afford
4bb; yield: 0.128 g (78%); white powder; mp 292–294 °C (Lit.6 mp
292–294 °C); Rf = 0.2 (CHCl3–CH2Cl2, 75:25).
1H NMR (400.13 MHz, DMSO-d6):  = 11.51 (br s, 1 H), 8.67 (d, J = 8.2
Hz, 1 H), 8.19 (d, J = 8.4 Hz, 2 H), 7.73 (d, J = 8.4 Hz, 2 H), 7.48–7.34 (m,
5 H), 7.29 (dd, J1 = 8.2 Hz, J2 = 0.8 Hz, 1 H), 7.02–6.96 (m, 1 H), 4.40 (q,
J = 7.1 Hz, 2 H), 1.39 (t, J = 7.1 Hz, 3 H).
13C NMR (100.6 MHz, DMSO-d6):  = 166.0 (CO2Et), 147.5 (q), 139.3
(q), 135.4 (q), 132.9 (q), 131.2 (CH), 130.5 (CH), 130.4 (q), 130.0 (CH),
129.8 (q), 129.3 (q), 124.4 (CH), 124.3 (CH), 123.8 (CH), 123.0 (CH),
118.7 (CH), 116.23 (CH), 116.20 (CH), 114.02 (q), 113.99 (q), 61.4
(CH2), 14.7 (CH3).
1H NMR (DMSO-d6):  = 11.41 (br s, 1 H), 8.64 (d, J = 8.0 Hz, 1 H), 7.50–
7.31 (m, 7 H), 7.26 (d, J = 7.5 Hz, 1 H), 7.20 (d, J = 8.7 Hz, 2 H), 6.99–
6.93 (m, 1 H), 3.87 (s, 3 H).
13C NMR (DMSO-d6):  = 159.4 (q), 147.6 (q), 135.2 (q), 132.8 (q),
131.9 (CH), 131.2 (q), 129.6 (CH), 128.9 (CH), 125.8 (q), 124.14 (CH),
124.09 (CH), 123.7 (CH), 122.9 (CH), 119.0 (CH), 116.1 (CH), 116.0 (q),
115.2 (CH), 115.0 (q), 114.5 (q), 55.6 (CH3).
12-(3-Methoxyphenyl)indolo[1,2-c]quinazolin-6(5H)-one (4bc)
Yield: 0.128 g (88%); pale yellow powder; mp 215–217 °C (Lit.6 mp
215–217 °C); Rf = 0.2 (CHCl3–CH2Cl2 75:25).
1H NMR (400.13 MHz, DMSO-d6):  = 11.44 (br s, 1 H), 8.65 (d, J = 8.2
Hz, 1 H), 7.56–7.46 (m, 2 H), 7.44–7.31 (m, 4 H), 7.27 (d, J = 8.0 Hz, 1
H), 7.13–7.06 (m, 3 H), 6.98 (t, J = 8.0 Hz, 1 H), 3.81 (s, 3 H).
13C NMR (100.6 MHz, DMSO-d6):  = 160.3 (q), 147.6 (q), 135.4 (q),
135.2 (q), 132.8 (q), 130.8 (overlapping, CH), 129.7 (CH), 128.9 (q),
124.2 (CH), 124.1 (CH), 123.9 (CH), 122.9 (CH), 122.8 (q), 118.9 (CH),
116.11 (CH), 116.07 (CH), 116.0 (CH), 115.1 (q), 114.3 (q), 114.2 (CH),
55.6 (CH3).
4-(6-Oxo-5,6-dihydroindolo[1,2-c]quinazolin-12-yl)benzonitrile
(4bd)
Yield: 0.107 g (75%); yellow powder; mp 262–264 °C (Lit.6 mp 262–
264 °C); Rf = 0.3 (n-hexane–EtOAc–MeOH 70:20:10).
5-Benzyl-12-(4-methoxyphenyl)indolo[1,2-c]quinazolin-6(5H)-
one (4aa)
1H NMR (400.13 MHz, DMSO-d6):  = 11.54 (br s, 1 H), 8.67 (d, J = 8.2
Hz, 1 H), 8.08 (d, J = 8.2 Hz, 2 H), 7.79 (d, J = 8.2 Hz, 2 H), 7.47–7.33 (m,
5 H), 7.29 (d, J = 8.2 Hz, 1 H), 7.04–6.97 (m, 1 H).
13C NMR (100.6 MHz, DMSO-d6):  = 147.5 (q), 139.5 (q), 135.4 (q),
133.7 (CH), 133.0 (q), 132.0 (CH), 130.2 (q), 130.1 (CH), 129.5 (CH),
124.48 (CH), 124.45 (CH), 123.8 (CH), 123.1 (CH), 119.3 (q), 118.6
(CH), 116.3 (overlapping, q, CH), 113.8 (q), 113.5 (q), 111.2 (q).
Yield: 0.145 g (79%); pale yellow powder; mp 181–183 °C; Rf = 0.2 (n-
hexane–EtOAc 75:25).
IR (KBr): 2924, 1690, 1384, 1250, 1030 cm–1
.
1H NMR (400.13 MHz, DMSO-d6):  = 8.69 (d, J = 8.3 Hz, 1 H), 7.62 (dd,
J1 = 8.0 Hz, J2 = 1.0 Hz, 1 H), 7.53–7.24 (m, 12 H), 7.19 (d, J = 8.8 Hz, 2
H), 7.06–7.00 (m, 1 H), 5.57 (s, 2 H), 3.88 (s, 3 H).
13C NMR (100.6 MHz, DMSO-d6):  = 159.5 (q), 148.3 (q), 137.1 (q),
135.3 (q), 133.2 (q), 131.9 (CH), 131.5 (q), 129.7 (CH), 129.2 (CH),
127.8 (q), 127.7 (CH), 127.0 (CH), 125.8 (CH), 124.4 (CH), 124.2 (CH),
123.2 (CH), 119.1 (CH), 116.4 (CH), 116.2 (CH), 115.9 (q), 115.3 (CH),
115.2 (CH), 55.7 (CH3), 46.4 (CH2).
HRMS: m/z [M + Na]+ calcd for C29H22N2O2Na: 453.1573; found:
453.1584.
12-(4-Tolyl)indolo[1,2-c]quinazolin-6(5H)-one (4be)
Yield: 0.057 g (41%); pale yellow powder; mp 210–212 °C; Rf = 0.3
(CHCl3–CH2Cl2 80:20).
IR (KBr): 3375, 2931, 1698, 1450 cm–1
.
1H NMR (400.13 MHz, DMSO-d6):  (as N-methyl derivative) = 8.68 (d,
J = 8.2 Hz, 1 H), 7.60 (d, J = 7.9 Hz, 1 H), 7.51–7.46 (m, 2 H), 7.45–7.41
(m, 5 H), 7.37–7.34 (m, 2 H), 7.10–7.04 (m, 1 H), 3.70 (s, 3 H), 2.47 (s,
3 H).
13C NMR (100.6 MHz, DMSO-d6):  (as N-methyl derivative) = 147.8
(q), 137.8 (q), 136.2 (q), 133.2 (q), 131.1 (q), 131.0 (q), 130.54 (CH),
130.48 (CH), 129.9 (CH), 127.8 (q), 124.34 (CH), 124.27 (CH), 123.9
(CH), 123.1 (CH), 119.0 (CH), 116.3 (CH), 115.8 (CH), 115.5 (q), 115.1
(q), 30.8 (CH3), 21.5 (CH3).
Ethyl 4-(5-Benzyl-6-oxo-5,6-dihydroindolo[1,2-c]quinazolin-12-
yl)benzoate (4ab)
Yield: 0.187 g (96%); pale yellow powder; mp 196–198 °C; Rf = 0.2 (n-
hexane–EtOAc 75:25).
IR (KBr): 2921, 1680, 1446, 1401, 1272, 1109 cm–1
.
1H NMR (400.13 MHz, DMSO-d6):  = 8.72 (d, J = 8.2 Hz, 1 H), 8.20 (d,
J = 8.4 Hz, 2 H), 7.76 (d, J = 8.4 Hz, 2 H), 7.54 (dd, J1 = 8.1 Hz, J2 = 1.1 Hz,
1 H), 7.51–7.45 (m, 1 H), 7.43–7.24 (m, 9 H), 7.07–7.00 (m, 1 H), 5.59
(s, 2 H), 4.40 (q, J = 7.1 Hz, 2 H), 1.39 (t, J = 7.1 Hz, 3 H).
HRMS: m/z [M – H]– calcd for C22H15N2O: 323.1190; found: 323.1191.
4-(6-Oxo-5,6-dihydroindolo[1,2-c]quinazolin-12-yl)benzaldehyde
13C NMR (100.6 MHz, DMSO-d6):  = 166.0 (CO2Et), 148.2 (q), 139.3
(q), 137.0 (q), 135.4 (q), 133.4 (q), 131.2 (CH), 130.7 (q), 130.6 (CH),
130.1 (CH), 129.9 (q), 129.2 (CH), 128.3 (q), 127.7 (CH), 127.0 (CH),
124.7 (CH), 124.3 (CH), 123.4 (CH), 118.9 (CH), 116.6 (CH), 116.4 (CH),
115.4 (q), 114.2 (q), 61.4 (CH2), 46.4 (CH2), 14.7 (CH3).
(4bf)
Yield: 0.134 g (93%); white powder; mp 266–268 °C; Rf = 0.2 (n-hex-
ane–EtOAc–MeOH 70:20:10).
IR (KBr): 3389, 2921, 2850, 1650, 1407, 1380 cm–1
.
HRMS: m/z [M + Na]+ calcd for C31H24N2O3Na: 495.1679; found
495.1689.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H

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A. Arcadi et al.
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1H NMR (400.13 MHz, DMSO-d6):  = 11.52 (br s, 1 H), 10.15 (br s, 1
H), 8.67 (d, J = 8.1 Hz, 1 H), 8.13 (d, J = 7.8 Hz, 2 H), 7.80 (d, J = 7.8 Hz,
2 H), 7.47–6.23 (m, 6 H), 6.96 (t, J = 7.5 Hz, 1 H).
13C NMR (100.6 MHz, DMSO-d6):  = 193.3 (CHO), 147.5 (q), 140.6 (q),
136.0 (q), 135.4 (q), 133.0 (q), 131.7 (CH), 130.8 (CH), 130.3 (q), 130.0
(CH), 129.4 (q), 124.40 (CH), 124.37 (CH), 123.8 (CH), 123.0 (CH),
118.7 (CH), 116.2 (CH), 114.0 (q), 113.9 (q).
13C NMR (100.6 MHz, DMSO-d6):  = 147.6 (q), 138.9 (q), 135.2 (q),
133.9 (q), 132.8 (q), 131.2 (CH), 130.9 (q), 129.64 (CH), 129.61 (CH),
129.2 (CH), 128.8 (q), 127.8 (CH), 124.2 (CH), 124.1 (CH), 123.8 (CH),
122.8 (CH), 119.0 (CH), 116.11 (CH), 116.07 (CH), 115.3 (q), 114.3 (q),
21.5 (CH3).
HRMS: m/z [M – H]– calcd for C22H15N2O: 323.1190; found: 323.1191.
HRMS: m/z [M – H]– calcd for C22H13N2O2: 337.0983; found: 337.0977.
12-(3-Nitrophenyl)indolo[1,2-c]quinazolin-6(5H)-one (4bk)
Yield: 0.130 g (86%); pale yellow powder; mp 268–270 °C; Rf = 0.2
(CHCl3–CH2Cl2 70:30).
12-(3-Chlorophenyl)indolo[1,2-c]quinazolin-6(5H)-one (4bg)
Yield: 0.074 g (50%); white powder; mp 274–276 °C; Rf = 0.2 (n-hex-
IR (KBr): 3376, 2925, 1384, 1107 cm–1
.
ane–EtOAc 70:30).
IR (KBr): 3389, 2923, 1701, 1450, 1402 cm–1
1H NMR (400.13 MHz, CDCl3):  = 9.87 (br s, 1 H), 8.62 (d, J = 8.2 Hz, 1
H), 7.51–7.24 (m, 8 H), 7.20–7.12 (m, 2 H), 6.94–6.87 (m, 1 H).
1H NMR (400.13 MHz, DMSO-d6):  = 11.54 (br s, 1 H), 8.67 (d, J = 8.2
Hz, 1 H), 8.40 (d, J = 8.2 Hz, 1 H), 8.36 (s, 1 H), 8.05 (d, J = 7.6 Hz, 1 H),
7.91 (t, J = 7.9 Hz, 1 H), 7.48–7.33 (m, 5 H), 7.30 (d, J = 8.3 Hz, 1 H),
6.98 (t, J = 7.6 Hz, 1 H).
.
13C NMR (100.6 MHz, DMSO-d6):  = 149.0 (q), 147.4 (q), 137.7 (CH),
135.9 (q), 135.4 (q), 132.9 (q), 131.4 (CH), 130.4 (CH), 129.8 (q), 125.4
(CH), 124.5 (CH), 124.4 (CH), 123.7 (CH), 123.5 (CH), 123.1 (CH), 118.5
(CH), 116.27 (CH), 116.26 (q), 113.8 (q), 112.6 (q).
13C NMR (100.6 MHz, CDCl3):  = 148.7 (q), 136.0 (q), 135.0 (q), 133.9
(q), 133.0, (q) 130.9 (q), 130.6 (CH), 130.4 (CH), 129.2 (CH), 128.8
(CH), 128.2 (CH), 124.4 (CH), 124.2 (CH), 124.1 (CH), 123.2 (CH), 118.7
(CH), 116.2 (CH), 115.4 (CH), 114.5 (q), 114.9 (q), 114.6 (q).
HRMS: m/z [M – H]– calcd for C21H12N3O3: 354.0884; found: 354.0886.
HRMS: m/z [M – H]– calcd for C21H12ClN2O: 343.0644; found:
343.0642.
Ethyl 4-(2-Methyl-6-oxo-5,6-dihydroindolo[1,2-c]quinazolin-12-
yl)benzoate (4ca)
Yield: 0.108 g (66%); white powder; mp 276–278 °C (Lit.6 mp 276–
278 °C); Rf = 0.2 (n-hexane–EtOAc–MeOH 70:20:10).
12-Phenylindolo[1,2-c]quinazolin-6(5H)-one (4bh)
Yield: 0.101 g (76%); white powder; mp 274–276 °C (Lit.6 mp 274–
276 °C); Rf = 0.2 (n-hexane–EtOAc 85:15).
1H NMR (400.13 MHz, DMSO-d6):  = 11.43 (br s, 1 H), 8.67 (d, J = 8.1
Hz, 1 H), 8.19 (d, J = 8.2 Hz, 2 H), 7.73 (d, J = 8.2 Hz, 2 H), 7.46–7.33 (m,
3 H), 7.26 (s, 1 H), 7.24–7.16 (m, 2 H), 4.40 (q, J = 7.1 Hz, 2 H), 2.07 (s,
3 H), 1.39 (t, J = 7.1 Hz, 3 H).
13C NMR (100.6 MHz, DMSO-d6):  = 166.0 (CO2Et), 147.5 (q), 139.3
(q), 133.2 (q), 133.0 (q), 131.8 (q), 131.3 (overlapping, CH), 130.9 (q),
130.39 (q), 130.37 (CH), 129.8 (q), 129.3 (q), 124.3 (CH), 123.8 (CH),
118.7 (CH), 116.2 (CH), 116.1 (CH), 113.9 (CH), 113.8 (q), 61.4 (CH2),
21.1 (CH3), 14.7 (CH3).
1H NMR (400.13 MHz, DMSO-d6):  = 11.49 (br s, 1 H), 8.70 (d, J = 8.2
Hz, 1 H), 7.71–7.56 (m, 5 H), 7.51–7.36 (m, 5 H), 7.32 (dd, J1 = 8.2 Hz,
J2 = 0.7 Hz, 1 H), 7.03–6.97 (m, 1 H).
13C NMR (100.6 MHz, DMSO-d6):  = 147.6 (q), 135.3 (q), 134.0 (q),
132.9 (q), 130.9 (q), 130.7 (CH), 129.75 (CH), 129.71 (CH), 128.9 (q),
128.6 (CH), 124.21 (CH), 124.17 (CH), 123.7 (CH), 122.8 (CH), 118.9
(CH), 116.14 (CH), 116.11 (CH), 115.2 (q), 114.3 (q).
2-(6-Oxo-5,6-dihydroindolo[1,2-c]quinazolin-12-yl)benzonitrile
(4bi)
12-(3-Methoxyphenyl)-2-methylindolo[1,2-c]quinazolin-6(5H)-
one (4cc)
Yield: 0.069 g (48%); pale yellow powder; mp 275–277 °C; Rf = 0.2 (n-
hexane–EtOAc–MeOH 70:20:10).
IR (KBr): 3399, 1551, 1252, 1008 cm–1
Yield: 0.111 g (56%); white powder; mp 246–278 °C; Rf = 0.2 (n-hex-
ane–EtOAc–MeOH 70:20:10).
.
1H NMR (400.13 MHz, DMSO-d6):  = 11.6 (br s, 1 H), 8.69 (d, J = 8.0
Hz, 1 H), 8.14 (d, J = 7.6 Hz, 1 H), 7.96 (t, J = 7.6 Hz, 1 H), 7.82–7.75 (m,
2 H), 7.50–7.26 (m, 5 H), 7.08 (d, J = 8.0 Hz, 1 H), 6.99 (d, J = 8.0 Hz, 1
H).
13C NMR (100.6 MHz, DMSO-d6):  = 147.4 (q), 137.8 (q), 135.4 (q),
134.7 (CH), 134.4 (CH), 132.8 (q), 132.6 (CH), 130.30 (q), 130.29 (q),
130.27 (CH), 129.9 (CH), 124.5 (overlapping, CH), 123.4 (CH), 123.3
(CH), 118.6 (CH), 118.2 (q), 116.4 (CH), 116.4 (CH), 113.9 (q), 113.7
(q), 111.0 (q).
IR (KBr): 3388, 2921, 1697, 1384, 1047 cm–1
.
1H NMR (400.13 MHz, DMSO-d6):  = 11.37 (br s, 1 H), 8.70–8.63 (m, 1
H), 7.53 (t, J = 7.8 Hz, 1 H), 7.44–7.29 (m, 4 H), 7.23–7.07 (m, 5 H), 3.82
(s, 3 H), 2.09 (s, 3 H).
13C NMR (100.6 MHz, DMSO-d6):  = 160.3 (q), 147.6 (q), 135.4 (q),
133.1 (q), 132.9 (q), 131.6 (q), 130.8 (q), 130.7 (CH), 130.6 (CH), 129.0
(q), 124.14 (CH), 124.12 (CH), 124.0 (CH), 123.0 (CH), 119.0 (CH),
116.1 (CH), 116.0 (CH), 115.99 (CH), 114.9 (q), 114.3 (CH), 114.1 (q),
55.7 (CH3), 21.2 (CH3).
HRMS: m/z [M – H]– calcd for C22H12N3O: 334.0987; found: 334.0987.
HRMS: m/z [M – H]– calcd for C23H17N2O2: 353.1296; found: 353.1298.
12-(3-Tolyl)indolo[1,2-c]quinazolin-6(5H)-one (4bj)
2-Methyl-12-phenylindolo[1,2-c]quinazolin-6(5H)-one (4ch)
Yield: 0.116 g (84%); beige powder; mp 235–237 °C; Rf = 0.2 (CHCl3–
CH2Cl2 80:20).
Yield: 0.085 g (62%); white powder; mp 230–231 °C; Rf = 0.2 (n-hex-
ane–EtOAc–MeOH 70:20:10).
IR (KBr): 3417, 2929, 1697, 1608, 1450, 1402 cm–1
.
IR (KBr): 3408, 2920, 1549, 1398 cm–1
.
1H NMR (400.13 MHz, DMSO-d6):  = 11.43 (br s, 1 H), 8.65 (d, J = 8.2
Hz, 1 H), 7.53–7.39 (m, 3 H), 7.38–7.30 (m, 6 H), 7.27 (d, J = 8.0 Hz, 1
H), 6.96 (t, J = 7.6 Hz, 1 H), 2.42 (s, 3 H).
1H NMR (400.13 MHz, DMSO-d6):  = 11.36 (br s, 1 H), 8.65 (d, J = 8.1
Hz, 1 H), 7.66–7.52 (m, 5 H), 7.39–7.32 (m, 3 H), 7.22 (s, 1 H), 7.21–
7.15 (m, 2 H), 2.05 (s, 3 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H

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A. Arcadi et al.
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Synthesis
13C NMR (100.6 MHz, DMSO-d6):  = 147.6 (q), 134.1 (q), 133.0 (q),
132.9 (q), 131.6 (q), 130.9 (q), 130.8 (CH), 130.6 (CH), 129.6 (CH),
129.0 (q), 128.6 (CH), 124.1 (CH), 123.8 (CH), 118.9 (CH), 116.1 (CH),
116.0 (CH), 115.1 (q), 114.1 (q), 21.1 (CH3).
13C NMR (100.6 MHz, DMSO-d6):  = 198.1 (CHO), 147.5 (q), 139.2 (q),
136.7 (q), 135.4 (q), 133.0 (q), 131.2 (CH), 130.5 (q), 130.0 (CH), 129.6
(CH), 129.3 (q), 124.40 (CH), 124.37 (CH), 123.8 (CH), 123.0 (CH),
118.7 (CH), 116.25 (CH), 116.23 (CH), 114.1 (q), 114.0 (q), 27.3 (CH3).
HRMS: m/z [M – H]– calcd for C22H15N2O: 323.1190; found: 323.1190.
HRMS: m/z [M – H]– calcd for C23H15N2O2: 351.1139; found: 351.1139.
2-Methyl-12-(m-tolyl)indolo[1,2-c]quinazolin-6(5H)-one (4cj)
Funding Information
Yield: 0.112 g (78%); pale yellow powder; mp 251–252 °C; Rf = 0.2 (n-
hexane–EtOAc–MeOH 70:20:10).
IR (KBr): 3380, 2921, 1696, 1450, 1397, 1120 cm–1
1H NMR (400.13 MHz, DMSO-d6):  = 11.35 (br s, 1 H), 8.66 (d, J = 8.1
Hz, 1 H), 7.50 (t, J = 8.0 Hz, 1 H), 7.45–7.31 (m, 6 H), 7.29 (s, 1 H),
7.22–7.15 (m, 2 H), 2.43 (s, 3 H), 2.07 (s, 3 H).
We gratefully acknowledge the University of l’Aquila and the Sapien-
za, University of Rome, for financial support.()
.
Supporting Information
13C NMR (100.6 MHz, DMSO-d6):  = 147.6 (q), 138.8 (q), 133.9 (q),
133.0 (q), 132.9 (q), 131.5 (q), 131.3 (CH), 130.8 (q), 130.5 (CH), 129.5
(CH), 129.1 (CH), 128.9 (q), 127.8 (CH), 124.1 (overlapping, CH), 123.9
(CH), 118.9 (CH), 116.1 (CH), 115.9 (CH), 115.2 (q), 114.2 (q), 21.5
(CH3), 21.1 (CH3).
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1610711.
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References
HRMS: m/z [M – H]– calcd for C23H17N2O: 337.1346; found: 337.1349.
(1) Ren, Z.-L.; Kong, H.-H.; Lu, W.-T.; Sun, M.; Ding, M.-W. Tetrahe-
dron 2018, 74, 184; and references cited therein.
(2) Honda, G.; Tabata, M.; Tsuda, M. Planta Med. 1979, 37, 172.
(3) Krivogorsky, B.; Nelson, A. C.; Douglas, K. A.; Grundt, P. Bioorg.
Med. Chem. Lett. 2013, 23, 1032.
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Subramanyam, D.; Venkateswarlu, A.; Rajagopal, S.; Kumar, K. B.
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2012, 53, 4248. (b) Gerfaud, T.; Wei, H.-L.; Zhu, J. Org. Lett. 2011,
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4-(10-Methyl-6-oxo-5,6-dihydroindolo[1,2-c]quinazolin-12-
yl)benzaldehyde (4df)
Yield: 0.097 g (65%); pale yellow powder; mp 286–288 °C; Rf = 0.2 (n-
hexane–EtOAc–MeOH 70:20:10).
IR (KBr): 3354, 2920, 2850, 1682 cm–1
.
1H NMR (400.13 MHz, DMSO-d6):  = 11.43 (br s, 1 H), 10.16 (s, 1 H),
8.53 (d, J = 8.4 Hz, 1 H), 8.15 (d, J = 8.2 Hz, 2 H), 7.81 (d, J = 8.2 Hz, 2 H),
7.44–7.34 (m, 2 H), 7.31–7.23 (m, 2 H), 7.16 (s, 1 H), 7.01–6.94 (m, 1
H), 2.40 (s, 3 H).
13C NMR (100.6 MHz, DMSO-d6):  = 193.3 (CHO), 147.4 (q), 140.8 (q),
136.0 (q), 135.4 (q), 133.6 (q), 131.7 (CH), 131.3 (q), 130.8 (CH), 130.6
(q), 129.9 (CH), 129.4 (q), 125.9 (CH), 123.7 (CH), 123.0 (CH), 118.2
(CH), 116.2 (CH), 115.9 (CH), 114.0 (q), 113.7 (q), 21.6 (CH3).
HRMS: m/z [M – H]– calcd for C23H15N2O2: 351.1139; found: 351.1141.
10-Methyl-12-phenylindolo[1,2-c]quinazolin-6(5H)-one (4dh)
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Lan, J.; You, J. Chem. Rev. 2017, 117, 8787.
Yield: 0.083 g (60%); pale yellow powder; mp 261–262 °C; Rf = 0.2 (n-
hexane–EtOAc–MeOH 70:20:10).
IR (KBr): 3455, 2924, 1606, 1513, 1400 cm–1
.
1H NMR (400.13 MHz, DMSO-d6):  = 11.42 (br s, 1 H), 8.51 (d, J = 8.5
Hz, 1 H), 7.66–7.58 (m, 2 H), 7.58–7.51 (m, 3 H), 7.40 (d, J = 7.7 Hz, 2
H), 7.38–7.32 (m, 1 H), 7.30–7.21 (m, 2 H), 7.12 (s, 1 H), 2.40 (s, 3 H).
13C NMR (100.6 MHz, CDCl3):  = 147.6 (q), 134.1 (q), 133.0 (q), 132.9
(q), 131.6 (q), 130.9 (q), 130.8 (q), 130.6 (CH), 129.6 (CH), 129.0 (CH),
128.6 (CH), 124.1 (CH), 123.8 (CH), 118.9 (CH), 116.1 (CH), 116.0 (CH),
115.1 (q), 114.1 (CH), 21.1 (CH3).
HRMS: m/z [M – H]– calcd for C22H15N2O: 323.1190; found: 323.1191.
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12-(4-Acetylphenyl)indolo[1,2-c]quinazolin-6(5H)-one (4bl′′)
Yield: 0.100 g (67%); pale yellow powder; mp 181–183 °C; Rf = 0.2 (n-
hexane–EtOAc 75:25).
IR (KBr): 3408, 2923, 1704, 1682, 1550, 1402, 1318 cm–1
.
1H NMR (400.13 MHz, DMSO-d6):  = 11.52 (br s, 1 H), 8.68 (d, J = 8.2
Hz, 1 H), 8.19 (d, J = 8.3 Hz, 2 H), 7.74 (d, J = 8.3 Hz, 2 H), 7.50–7.35 (m,
5 H), 7.30 (d, J = 7.4 Hz, 1 H), 7.02–6.96 (m, 1 H), 2.70 (s, 3 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H

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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H