Copper-Catalyzed C–C Bond Cleavage/Double Cyclization of α-Ketoamides with o-Phenylene Diamines: Synthesis of Benzimidazo[1,2-c]quinazolin-6-ones

Article abstract of DOI:10.1002/ejoc.201901642

A highly regioselective C–C bond cleavage/double cyclization of α-ketoamides with o-phenylene diamines has been developed for the synthesis of benzimidazo[1,2-c]quinazolin-6-ones. Two new C–N and one new C=N bonds are simultaneously formed in the reaction, providing the gateway to access these fused heterocyclic scaffolds via copper catalysis under air atmosphere. This new protocol provides a novel and important foundation for the preparation of these heterocycles.

Full text of DOI:10.1002/ejoc.201901642

A Journal of
Accepted Article
Title: Copper-Catalyzed Tandem C–C Bond Cleavage/Double
Cyclization of α-Ketoamides with o-Phenylene Diamines:
Synthesis of Benzimidazo[1,2-c]quinazolin-6-ones
Authors: Lianghua Zou, Cheng Yan, Kai Shi, Liang Su, Shuai Zhu,
Zhe-Kang Jia, and Qiuan Wang
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201901642
Link to VoR: http://dx.doi.org/10.1002/ejoc.201901642
Supported by

European Journal of Organic Chemistry
10.1002/ejoc.201901642
COMMUNICATION
Copper-Catalyzed C–C Bond Cleavage/Double Cyclization of α-
Ketoamides with o-Phenylene Diamines: Synthesis of
Benzimidazo[1,2-c]quinazolin-6-ones
,
[a]
[a],‡
[a]
[b]
[a]
[a]
[a],[b]
Liang-Hua Zou,* Cheng Yan,
Kai Shi, Liang Su, Shuai Zhu, Zhe-Kang Jia, Qiuan Wang*
ABSTRACT: A highly regioselective C–C bond cleavage/double
cyclization of α-ketoamides with o-phenylene diamines has been
developed for the synthesis of benzimidazo[1,2-c]quinazolin-6-
ones. Two new C–N and a new C=N bonds are simultaneously
formed in the reaction, providing the gateway to access these
fused heterocyclic scaffolds via copper catalysis under air
atmosphere. This new protocol provides a novel and important
foundation for the preparation of these heterocycles.
benzoimidazoles with ethyl chloroformate in pyridine
[
7]
(
Scheme 1, Eq. c); (iv) Amidinyl radical formation through
[8]
anodic N–H bond cleavage (Scheme 1, Eq. d); (iv) the
oxidative cyclization of o-phenylene diamines with indole
derivatives (Scheme 1, Eq. e and f). Despite these
[9]
advances, the synthesis of imidazo[1,2-c]quinazolin-6-ones
still suffers from some limitations, such as the requirement
of multistep synthesis of the precursors, expensive
reagents and/or limited substrate scope and high reaction
temperature. In view of the importance of these compounds,
it is still in strong desire to explore new methodologies to
[
9a,10]
synthesize such heterocycles.
and efficient method for the synthesis of benzimidazo[1,2-
c]quinazolin-6-ones using aldehyde-substituted α-
ketoamides and o-phenylene diamines as starting materials
Scheme 1, Eq. g).
Herein, we report a new
Introduction
Considerable efforts have been devoted to the development
of synthetic strategies that rapidly construct diverse and
complex molecular structures, not only for the total
synthesis of natural products but also to provide practical
and sustainable methods for the preparation of bioactive
compounds, such as pharmaceuticals, agrochemicals, and
(
[
1]
various heterocycles. In this regard, remarkable attention
has been paid to the synthesis of benzimidazole and
quinazolinone derivatives, which are widely found in natural
products or synthetic medicines, due to their broad range of
biological and medical activities, including antidiabetic,
analgesic, antiviral, chemotherapeutic, antifungal, and so
[
2]
on.
represent a class of important heterocycles with potential
activities in pharmaceuticals, such as compounds and
which are potent antihypertensive agents selectively
In
particular,
imidazo[1,2-c]quinazolin-6-ones
A
B
[
3]
antagonize the α1-adrenoceptor. Besides, studies show
that CGS-1761 has weak anxiolytic profiles (Figure 1).
[
4]
Figure 1. Representative imidazo[1,2-c]quinazolin-6-ones.
Over the past years, various protocols have been
developed for the synthesis of such compounds, including
(
i) A tandem Aza-Wittig reaction/heterocumulene-mediated
[5]
annulations reaction (Scheme 1, Eq. a); (ii) The reductive
cyclization of 2-(2-nitrophenyl)benzoimidazoles with
isocyanates promoted by low-valent titanium reagent
[
6]
(Scheme 1, Eq. b); (iii) The reaction of 2-(2-aminophenyl)
[
a]
Prof. Dr. L.-H. Zou, C. Yan, K. Shi, S. Zhu, Z.-K. Jia, Prof. Dr.
Q. Wang
The Key Laboratory of Carbohydrate Chemistry and
Biotechnology, Ministry of Education, School of
Pharmaceutical Sciences, Jiangnan University, Lihu Avenue
1800, Wuxi 214122, P.R. China
Scheme 1. Methods for the synthesis of benzimidazo[1,2-c]quinazolin-6-ones.
Email: zoulianghua@jiangnan.edu.cn
Homepage: http://sps.jiangnan.edu.cn
L. Su, Prof. Dr. Q. Wang
Results and Discussion
[
b]
College of Chemistry and Chemical Engineering, Hunan
University, Changsha 410082, P.R. China
Email: wangqa@hnu.edu.cn
The initial optimization of the reaction conditions was
conducted by using 1a and 2a as substrates and all the
results are summarized in Table 1. Using 1a and 2a at a 1:1
ratio (on 0.2 mmol scale), CuI (10 mol %) as catalyst,
Supporting information for this article is available on the
WWW under https://www.eurjoc.com.
‡
L.Z. and C.Y. contributed to this work equally.
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European Journal of Organic Chemistry
10.1002/ejoc.201901642
COMMUNICATION
Cs
2
CO
3
(3.0 equiv) as base and EtOH as solvent, the
18). Furthermore, the yield was enhanced to 81% by
optimizing the ratio of 1a and 2a (Table 1, entries 19-21).
Besides, several other bases, such as tBuOK, tBuOLi,
desired product 3a was obtained in 15% yield after stirring
Table 1. Optimization of reaction conditions for the
2 3 3 4
K CO and K PO , were investigated in the reaction, albeit
a
synthesis of 3a
.
giving lower yields (Table 1, entries 22-25). Product 3a was
formed only in trace amounts when no base was used in
the reaction (Table 1, entry 26).
a
Table 2. The substrate scope of Α-ketoamides.
b
Entry
Catalyst
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
Base
Solvent
EtOH
EtOH
DCE
Yield (%)
c
1
2
3
4
5
6
7
8
9
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Ct s
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
15
30
35
24
33
MeOH
Entry
1
R =
Ar =
Product
Yield
%)
CH
DMSO
CHCl
3
CN
(
trace
trace
43
1
2
3
4
1
1b
1
1d
a
H
Ph
Ph
Ph
Ph
3a
3b
3c
3d
81
73
70
55
3
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
2-OMe
3-OMe
2,3-(-O-
d
c
CuI
CuI
43
e
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
trace
51
43
49
34
24
trace
trace
Cu(OAc)
CuBr
2
2
CH -O-)
5
6
7
8
9
10
11
12
13
14
15
1
1f
1g
e
2-F
2-Cl
2-Br
3-F
3-Cl
3-Br
3-CF
H
Ph
Ph
Ph
Ph
Ph
3e
3f
3g
3h
3i
75
76
72
55
66
62
82
48
60
56
47
CuBr
Cu
2
0
1
h
Cu(OTf)
2
CuO
/
1i
1j
1
1l
1m
Ph
Ph
3j
f
k
3
3k
3a
3a
3a
3a
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
2
2
2
2
2
2
2
2
2
75
f,g
55
2-Naphth
4-Me-Ph
4-Cl-Ph
2,4-
f,h
77
H
H
H
f,i
1
n
81
f,i
BuOK
BuOLi
48
51
43
30
1o
t
f,i
Dichloro-Ph
2-Thienyl
f,i
16
1
p
H
3a
58
K
2
CO
3
f,i
K
3
PO
/
4
a
f,i
Reaction conditions: (a) The first step: 1 (0.23 mmol) and 2a
(0.2 mmol) in DMF (2 mL) were stirred in a sealed tube at 110
o
trace
a
Reaction conditions A: 1a (0.2 mmol), 2a (0.2 mmol), catalyst
10 mol %), base (3.0 equiv), solvent (2 mL), air atmosphere,
C under air atmosphere for 12 h; (b) The second step:
Cu(OAc) (10 mol %) and Cs CO (3.0 equiv) were added into
b
(
1
2
2
3
o
b
o
10 C, 12 h, in
a
sealed tube. Yield after column
the mixture, which was stirred at 130 C for additional 12 h.
c
o
d
chromatography based on compound 2a. 80 C. Dioxygen
Yield after column chromatography based on compound 2a.
e
f
atmosphere. Argon atmosphere. Reaction conditions B: 1a
0.2 mmol) and 2a (0.2 mmol) in DMF (2 mL) were stirred in a
With the optimized reaction conditions in hand (Table 1,
entry 21), the scope of the reactions using a series of α-
(
o
sealed tube at 110 C under air atmosphere for 12h. Cu(OAc)
10 mol %) and Cs CO (3.0 equiv) were then added into the
reaction mixture, which was stirred at 130 C for additional 12 h.
2
ketoamides
1 and 2a was investigated and the results are
(
2
3
o
summarized in Table 2. Various substrates with electron-
donating or electron-withdrawing substituents were applied
to the reaction system to provide benzimidazo[1,2-
g
h
i
Ratio of 1a and 2a = 1:1.5. Ratio of 1a and 2a = 1.5:1. Ratio of
1
a and 2a = 1.15:1.
c]quinazolin-6-ones 3a–3k. For example, the reaction of
o
at 110 C for 12 h (Table 1, entry 1). The yield was
enhanced to 30% when the temperature was raised to 110
substrates bearing electron-donating –OMe group at
different positions afforded the corresponding products 3b
and 3c in 73% and 70% yields, respectively (Table 2,
o
C (Table 1, entry 2). Next various solvents were screened
for their influence on the reaction behaviour and DMF
proved to be the best solvent for this reaction, providing
product 3a in 43% yield (Table 1, entries 3-8). Product 3a
was obtained in the same yield under an atmosphere of
dioxygen, but product 3a was formed only in trace amounts
under argon, indicating that the dioxygen (regardless of the
content) played an important role in the reaction (Table 1,
entries 2 and 3). Besides, another electron-donating
substrate also reacted well to furnish product 3d in 55%
yield (Table 2, entry 4). In addition, substrates with halogen
groups such as –F, –Cl and –Br also worked well in the
procedure, producing the corresponding products 3e–3g in
75%, 76% and 72% yields, respectively (Table 2, entries 5-
7). Considering the possible influence of steric factor, the
reaction was turned to other substrates with halogen groups
–F, –Cl and –Br at different positions, affording products
[
11]
entries 9 and 10). Further studies showed that Cu(OAc)
2
proved to be the best catalyst for this reaction, providing
product 3a in 51% yield (Table 1, entries 11-16). However,
only trace amounts of product 3a was observed without
catalyst (Table 1, entry 17). Considering the fact that it
might be a sequential-step process for the formation of
product 3a, we turned our attention to adding the reaction
components step by step. This strategy was successfully
3h
8-10). Furthermore, one substrate bearing strong electron-
withdrawing substituent –CF was also successfully
–3j in yields varying from 55% to 66% (Table 2, entries
3
employed in the reaction, giving product 3k in 82% yield
(Table 2, entry 11). It appeared that various electron-
donating and electron-withdrawing substituents were well
realized as two steps for the transformation: a) the first step: tolerated in the reaction and there was no straightforward
o
The reaction was stirred at 110 C for 12 hours in the
absence of catalyst and base; 2) the second step: After
correlation between the electronic properties of the
substituents and reaction efficiency. However, the steric
properties of the substrates apparently played an important
role on the reaction efficiency (75% yield of 3e vs. 55%
yield of 3h; 76% yield of 3f vs. 66% yield of 3i; 72% yield of
adding Cu(OAc) (10 mol %) and Cs CO (3.0 equiv), the
2 2 3
reaction was stirred at 130 C for additional 12 hours. In this
case, product 3a was isolated in 75% yield (Table 1, entry
o
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European Journal of Organic Chemistry
10.1002/ejoc.201901642
COMMUNICATION
3
g
vs. 62% yield of 3j). Finally, a series of α-ketoamides
expected a mixture of products were provided for all of
them. Among them, the substrate bearing –F group
afforded a mixture of 3o and 3o' in 40% yield (the ratio of
bearing different aromatic substituents were tested in the
reaction (Table 2, entries 12-16). Although it appeared that
no better yields were obtained, all the tested examples
the two isomers was 3:4). The substrate bearing
afforded a mixture of 3p and 3p in 76% yield (the ratio of
the two isomers was 2:3). The substrate bearing Br group
afforded a mixture of 3q and 3q in 51% yield (the ratio of
–Cl group
(including one substrate bearing a thienyl group) worked
'
well.
–
'
the two isomers was 1:1). Furthermore, we investigated the
substrates bearing such substituents at 3,4-positions. To
our delight, all these substrates reacted well with compound
1a, affording the corresponding products 3r–3t in good
yields varying from 62% to 80% yields. To test the
scalability of the new protocol, we performed the reaction
on a 2.0 mmol scale under the optimized conditions,
affording product 3a (286.8 mg) in a good yield of 61%.
Scheme 3. Control reactions.
In order to elucidate the possible mechanism, several
control experiments were conducted (Scheme 3). Initially, a
by-product
5 was isolated in 25% yield, along with the
generation of product 3a in 51% yield when the reaction
was performed under the conditions as in entry 11 of table
1
(Scheme 3, Eq. a). By analysing the structure of
compound , we believed that this compound might be
produced via the reaction of compound 2a with
benzaldehyde , which derived from 1a as a leaving group.
In order to verify our hypotheses, a control reaction was
performed using benzaldehyde and 2a as starting
materials under the conditions as in entry 11 of table 1,
affording the by-product in 59% yield (Scheme 3, Eq. b).
In contrast to the above-mentioned results (Table 1,
entry 21), by-product was obtained only in trace amounts
5
4
4
Scheme 2. The substrate scope of o-phenylene diamines 2.
Reaction conditions: (a) The first step: 1a (0.23 mmol), 2
o
5
(
0.2 mmol), DMF (2 mL), air atmosphere, 110 C, 12 h; (b) The
second step: Cu(OAc) (10 mol %) and Cs CO (3.0 equiv) were
2 2 3
o
5
added and the reaction was stirred at 130 C for additional 12 h.
b
when the reaction was carried out under the standard
conditions, which appeared reasonable since it was a
matter of two competitive reactions. In the former case, the
The ratio of the two isomers in the mixture was determined by
H NMR analysis. Yield after column chromatography based on
1
c
compound 2.
generated benzaldehyde
4 would react with compound 2a
In order to further explore the scope of the reaction, the
in the whole reaction process. In the latter case, the starting
reactions of various o-phenylene diamines
2
with 1a were
material 2a would be consumed up at the first step to form
investigated and the results are summarized in Scheme 2.
The reactions of the substrate bearing methyl group at the
an intermediate, so that compound 5 was not formed. In
order to verify our assumption that the reaction might
proceed via two steps, a control reaction was performed
using 1a and 2a as substrates without catalyst and base
(Scheme 3, Eq. c). To our delight, intermediate 3a' was
3-position with 1a exhibited excellent regioselectivities,
providing product 3l in 60% yield. When choosing a
substrate containing methyl group at the 5-position, a
mixture of products 3m and 3m' were obtained in 55% yield. isolated in 81% yield and the structure of 3a' was
It should be noteworthy that it was difficult to isolate the two
isomers and we could only know that the ratio of the
isomers in the mixture was 1:2. One substrate with two
methyl groups at the 3,4-positions was also tested in the
reaction, providing the desired product 3n in a good yield of
unambiguously determined by X-ray crystallography.
Besides, a control reaction was carried out using 3a'
instead of 1a in the absence of 2a under the standard
conditions, affording product 3a in 85% yield, which further
indicated that 3a' might be the intermediate generated in
the reaction (Scheme 3, Eq. d). Furthermore, radical
scavengers, such as 2,2,6,6-tetramethyl-1-piperidinyloxy
51%. Subsequently, various halogen groups, such as –F, –
Cl and –Br, were investigated in the procedure. As
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European Journal of Organic Chemistry
10.1002/ejoc.201901642
COMMUNICATION
(
TEMPO) and 2,6-bis(1,1-dimethylethyl)-4-methyl-phenol
BHT), were added in the reaction in the second step of
Acknowledgements
(
standard conditions, providing product 3a in 66% and 64%
yields, respectively, which indicates that a radical pathway
might not be involved in this reaction (Scheme 3, Eq. e).
This work is financially supported by NSF of Jiangsu Province
BK20150129), Top-notch Academic Programs Project of
Jiangsu Higher Education Institutions (No. PPZY2015B146).
(
[
9a,12]
Based on these results and previous reports,
possible mechanism is proposed for this reaction
Scheme 4). Taking the synthesis of 3a as a representative
example, 1a reacts with 2a to generate intermediate
which undergoes 5-exo-tet cylization to furnish intermediate
a
Keywords: Benzimidazo[1,2-c]quinazolin-6-ones • Double
Cyclization • α-Ketoamides • o-Phenylene diamines • Copper
catalysis
(
I
,
[
13]
II
intermediate 3a'
deprotonation and transmetalation in the presence of
.
The subsequent aerobic oxidation of II affords
[1]
For a themed issue on the rapid formation of complexity in
[
13]
,
which affords intermediate III by
organic synthesis, see: a) H. M. L. Davies, E. J. Sorensen, Chem.
Soc. Rev. 2009, 38, 2981–3272; b) J. Cossy, S. Arseniyadis,
Modern tools for the synthesis of complex bioactive
[
12]
Cs
2
CO
3
and copper(II) acetate.
Then an intramolecular
attack of nitrogen atom to ketone provides intermediate IV
molecules, Wiley-VCH, Weinheim, 2012
.
[
9a]
with the aid of a hydrogen ion,
intermediate , along with the generation of benzaldehyde
Notably, compound reacts with 2a to give by-product
, which is detected by GC MS analysis. Finally, the
which further transforms
[2]
a) F. R. Alexandre, A. Berecibar, R. Wrigglesworth, T. Besson,
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C.-W. Bi, Y.-N. Zhang, J.-Q. Xu, J.-X. Wang, M.-G. Zhou,
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Scarlato, T. Gibson, P. D. van Poelje, S. C. Potter, M. D. Erion, J.
Med. Chem. 2010, 53, 441–451; e) M. Gaba, D. Singh, S. Singh,
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V
[
14]
4
5
.
4
-
desired product 3a is produced through the tautomerism of
intermediate
V.
[
3]
a) J.-W. Chern, P.-L. Tao, K.-C. Wang, A. Gutcait, S.-W. Liu, M.-
H. Yen, S.-L. Chien, J.-K. Rong, J. Med. Chem. 1998, 41, 3128–
3
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2
[
[
4]
5]
J. E. Francis, W. D. Cash, B. S. Barbaz, P. S. Bernard, R. A.
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2
81–290.
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–
4
3
.
Scheme 4. Proposed mechanism for the synthesis of 3a.
[
[
6]
7]
.
.
Conclusions
[8]
H.-B. Zhao, Z.-W. Hou, Z.-J. Liu, Z.-F. Zhou, J. Song, H.-C. Xu, Angew.
Chem. Int. Ed. 2017, 56, 587–590; Angew. Chem. 2017, 130,
1
5373–15736.
In summary, an efficient and practical protocol for the
construction of benzimidazo[1,2-c]quinazolin-6-ones via the
reactions of α-ketoamides and o-phenylene diamines has
been developed. The reactions are operationally simple
involving copper-catalyzed C–C bond cleavage and multiple
new C–N bonds formation under air atmosphere. Notably, a
series of products have been obtained in good yields by
using this method, some of which were difficult to prepare
before.
[
9]
a) P.-G. Li, C. Yan, S. Zhu, S.-H. Liu, L.-H. Zou, Org. Chem. Front.
2018, 5, 3464–3468; b) Z. Dai, S. Li, Y. Li, L. Feng, C. Ma,
Tetrahedron 2019, 75, 2012–2017.
[10] For our recent work on heterocycles, see: a) L.-H. Zou, H. Zhu, S.
Zhu, K. Shi, C. Yan, P.-G. Li, J. Org. Chem. 2019, 84, 12301–12313
;
b) L.-H. Zou, C. Zhao, P.-G. Li, Y. Wang, J. Li, J. Org. Chem. 2017, 82,
12892−12898; c) P.-G. Li, H. Zhu, M. Fan, C. Yan, K. Shi, X.-W. Chi,
L.-H. Zou, Org. Biomol. Chem. 2019, 17, 5902–5907; d) P.-G. Li, Y.
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Org. Chem. 2016, 5, 625–628; For other selected examples on
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Song, Y. Liu, M. Hu, P. Xie, J.-H. Li, Angew. Chem. Int. Ed. 2013, 52,
Experimental Section
Take the synthesis of 3a as one example. To a 25 mL sealed
tube equipped with a magnetic stirring bar was added 1a (0.23
mmol, 58.2 mg, 1.15 equiv), 2a (0.2 mmol, 21.6 mg, 1.0 equiv)
3
638–3641; Angew. Chem. 2013, 125, 3726–3729; g) M. Hu, J.-H.
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under an atmosphere of air. After the addition of anhydrous DMF
o
(
2 mL), the reaction was stirred at 110 C for 12 h. After cooling
to room temperature, anhydrous Cu(OAc)
.1 equiv) and Cs CO (0.6 mmol, 195.5 mg, 3.0 equiv) were
added into the sealed tube and stirred at 130 C for additional
2 h. The reaction mixture was extracted with methyl tert-butyl
ether (5 × 30 mL) and washed with brine. The organic phase
was dried over anhydrous Na SO and concentrated under
2
(0.02 mmol, 3.6 mg,
2
016, 55, 3187–3191; Angew. Chem. 2016, 128, 3239–3243.
0
2
3
o
[11] For selected reactions involving dioxygen, see: a) Y. Li, J.-H. Li, Org.
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1
2
4
reduced pressure. Crude product was purified by flash
chromatography on silica gel using eluent (PE/EA = 5:1),
affording the desired product 3a as a white solid (0.162 mmol,
9
08−912; e) C. Liu, Q. Lu, Z. Huang, J. Zhang, F. Liao, P. Peng, A. Lei,
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38.1 mg) in 81% yield.
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European Journal of Organic Chemistry
10.1002/ejoc.201901642
COMMUNICATION
2
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47.
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European Journal of Organic Chemistry
10.1002/ejoc.201901642
COMMUNICATION
COMMUNICATION
Heterocycle synthesis
Liang-Hua Zou,* Cheng Yan, Kai Shi,
Liang Su, Shuai Zhu, Zhe-Kang Jia, Qiuan
Wang*
Page No. – Page No.
Copper-Catalyzed
C–C
Bond
α-Ketoamides have been successfully employed to synthesize benzimidazo[1,2-
c]quinazolin-6-ones through C–C bond cleavage/double cyclization, in which two new C–
N and a new C=N bonds are simultaneously formed via copper catalysis under air
atmosphere. This new protocol provides a novel and important foundation for the
preparation of these heterocycles, providing a series of benzimidazo[1,2-c]quinazolin-6-
ones in high yields.
Cleavage/Double
Ketoamides with o-Phenylene Diamines:
Synthesis of Benzimidazo[1,2-c]quinazolin-
Cyclization
of
α-
6-ones
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