Copper-Catalyzed Intramolecular α-C-H Amination via Ring-Opening Cyclization Strategy to Quinazolin-4-ones: Development and Application in Rutaecarpine Synthesis

Article abstract of DOI:10.1055/s-0037-1611575

A copper-catalyzed intramolecular α-C-H amination has been developed for the synthesis of quinazolin-4(3 H)-one derivatives from commercially available isatoic anhydride and primary and secondary benzylamines via ring-opening cyclization (ROC). This method shows good functional group tolerance and allows access to a range of 2-aryl, 2-alkyl, and spiroquinazolinone derivatives. However, 2-methylquinazolin-4(3 H)-one was synthesized from 2-amino- N -isopropylbenzamide by C-C bond cleavage, and N -benzyl-2-(methylamino)benzamide afforded 1-methyl-2-phenylquinazolin-4(1 H)-one along with 2-phenylquinazolin-4(3 H)-one by N-C bond cleavage for aromatization. It is the first general method to construct the potentially useful 2-methylquinazolin-4(3 H)-one by copper-catalyzed intramolecular C-H amination. Also this ROC strategy has been successfully applied to the synthesis of quinazolinone alkaloid rutaecarpine.

Full text of DOI:10.1055/s-0037-1611575

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–K
paper
A
en
S. M. Patel et al.
Paper
Synthesis
Copper-Catalyzed Intramolecular -C–H Amination via Ring-
Opening Cyclization Strategy to Quinazolin-4-ones: Development
and Application in Rutaecarpine Synthesis
Srilaxmi M. Patela
O
O
Harika Chadab
Sonali Biswala
Sonika Sharmab
N
N
O
O
N
CuBr (15 mol%)
N
N
H
HN
KOtBu (2 equiv)
N
O
rutaecarpine
O
Duddu S. Sharada*a
0
0
0
0-
0
0
0
1-5
8
6
1-4
1
2
6
toluene
100 °C
O
O2, DMSO, 100 °C
NH2
N
H
O
NH
a Catalysis & Chemical Biology Laboratory, Department of
Chemistry, Indian Institute of Technology (IIT) Hyderabad,
Kandi, Sangareddy, Telangana 502 285, India
b Loyola Academy Degree & P. G College, Old Alwal,
Secunderabad, Telangana 500010, India
NH
N
H
Cross-dehydehydrogenative Intramolecular sp3 C–H amination
Predictable regioselectivity
Easily accessible starting materials
N
H
R
25 examples
up to 70% yield
Development of new ROC strategy to rutaecarpine
sharada@iith.ac.in
Received: 05.01.2019
Accepted after revision: 19.03.2019
Published online: 15.04.2019
tion11a and also, in recent past reported on the direct cyclo-
aminative approach to imidazole derivatives via dual C–H
functionalization.11b
DOI: 10.1055/s-0037-1611575; Art ID: ss-2019-z0004-op
O
Abstract A copper-catalyzed intramolecular -C–H amination has
been developed for the synthesis of quinazolin-4(3H)-one derivatives
from commercially available isatoic anhydride and primary and second-
ary benzylamines via ring-opening cyclization (ROC). This method
shows good functional group tolerance and allows access to a range of
2-aryl, 2-alkyl, and spiroquinazolinone derivatives. However, 2-meth-
ylquinazolin-4(3H)-one was synthesized from 2-amino-N-isopropylben-
zamide by C–C bond cleavage, and N-benzyl-2-(methylamino)ben-
zamide afforded 1-methyl-2-phenylquinazolin-4(1H)-one along with 2-
phenylquinazolin-4(3H)-one by N–C bond cleavage for aromatization. It
is the first general method to construct the potentially useful 2-meth-
ylquinazolin-4(3H)-one by copper-catalyzed intramolecular C–H amina-
tion. Also this ROC strategy has been successfully applied to the synthe-
sis of quinazolinone alkaloid rutaecarpine.
O
N
NH
N
N
HN
2-methyl-4(3H)-quinazolinone
rutaecarpine
O
N
O
N
R
N
N
O
N
tryptanthrin
luotonin A, B, E
Figure 1 Quinazolinone skeleton containing natural products
Key words intramolecular C-H amination, ring-opening cyclization,
rutaecarpine, quinazolin-4(3H)-one, 2-methylquinazolin-4(3H)-one
Over the past three decades, considerable progress has
been made in the development of methods to construct sp2
carbon–nitrogen (C–N) bonds using palladium, copper, or
nickel catalysis. However, formation of sp3 C–N bonds re-
mains one of the major challenges in the field of cross-cou-
pling chemistry. Recently, much attention has been focused
towards the development of transition-metal-catalyzed in-
tramolecular C–H amination strategies to assemble N-het-
erocyclic compounds.12 In most of the cases, a tertiary
amine has been used as one of the partners whereas -C–H
bond has been activated. In 2010, Maiti and co-workers re-
ported cross-dehydrogenative sp3 C–O bond formation an
iminium ion from amide to construct dihydro-oxazinone
derivatives,13a and also recently Maiti’s group reported cop-
per-catalyzed C(sp3)–H functionalization/cyclization of 2-
amino-N,N-dialkylbenzamides for the synthesis of 2,3-
disubstituted 4(3H)-quinazolinone derivatives.13b Applica-
tion of this strategy in intramolecular C–heteroatom bond
Quinazolinone is an important N-heterocyclic scaffold,
as seen by their abundance in biologically active com-
pounds and numerous natural products such as rutae-
carpine,1 tryptanthrin,2 luotonin A, B, E, and F,3 and bioac-
tive compounds (Figure 1). Owing to the promising bio-
logical and medicinal activities including anticancer,4 anti-
inflammatory,5 antibacterial,6 and antihypertensive7 prop-
erties, synthetic quinazolinone scaffolds have been highly
in demand and remains a challenge in organic synthesis.
The direct functionalization of C–H bonds of organic com-
pounds has recently emerged as a diverse atom economic
carbon–heteroatom (C–X)8 and carbon–carbon (C–C) bond
formation.9 Several diverse C–H functionalization method-
ologies without prefunctionalization of the coupling part-
ners have been widely developed in the past decades.10 Pre-
viously, we have employed N-incorporation strategy for the
synthesis of quinoxalines via dual C(sp2)–H functionaliza-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

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S. M. Patel et al.
Paper
Synthesis
O
O
N
NH
NH
R5
N
H
R5 = alkyl
4 examples
up to 65% yield
2.
CuBr (15 mol%)
KOtBu (2 equiv), O2
DMSO, 100 °C
NH2
1.
R5
R
2 = H, toluene
24 h
NH
1.
R4
O
N
O
O
N
H
R3
1.
N
H
R4
N
N
N
O
R1
toluene
toluene
R1
2.CuBr (15 mol%)
KOtBu (2 equiv), O2
DMSO, 100 °C
R2 = H, R4 = H/alkyl
N
R2
O
HN
2.
CuBr (15 mol%)
KOtBu (2 equiv), O2
DMSO, 100 °C
R3
rutaecarpine
60% yield
12 h
quinazolin-4(3H)-one
2. CuBr (15 mol%)
KOtBu (2 equiv), O2
DMSO, 100 °C
18 examples
2–5 h
2 = Me, R4 = H
toluene, 100 °C
up to 70% yield
1.
R
O
O
N
N
NH
R1
R1
+
N
R3
R3
quinazolin-4(3H)-ones
quinazolin-4(1H)-ones
up to 34% yield
up to 38% yield
3 examples
Scheme 1 Our present strategy for the synthesis of quinazolinone derivatives
formation to synthesize challenging heterocycles and phar-
maceutically important compounds is less studied. Newly
established methodology leading to the natural products is
in high demand for modern organic synthesis.14
In this context, we are pleased to report intramolecular
cross-dehydrogenative coupling for C–N bond formation
under aerobic conditions for the synthesis of quinazolin-
4(3H)-ones from isatoic anhydride and amines (benzylic
and aliphatic) with copper(I) catalyst via ring-opening cy-
clization (ROC) strategy (Scheme 1). During this process an
iminium ion intermediate is formed, which is subsequently
trapped by an amine nucleophile.
Rutaecarpine, as a kind of natural quinazolinecarboline
alkaloid was isolated from fruits of Evodia rutaecarpa, a
plant used for treatment of headache, cholera, and dysen-
tery in Chinese medicine. Due to the medicinal importance
of this alkaloid, various synthetic routes have been devel-
oped.1a,15 Recently Jieping Zhu et al. synthesized rutae-
carpine and (±)-evodiamine by a silver salt-catalyzed inser-
tion of the isocyano group into the N–H bond of the trypt-
amine followed by in situ lactamization.16 Herein, we
describe a shorter route to rutaecarpine from isatoic anhy-
dride and tryptoline via ROC strategy.
90 °C in DMSO, which afforded 2-phenylquinazolin-4(3H)-
one (4a) in 45% yield (Table 1, entry 1).
Further screening of various copper(II) and copper(I)
catalyst could promote the reaction and CuBr was found to
be the optimal choice (Table 1, entries 1–6). To improve the
yield of the product different bases were screened with
CuBr and DMSO as solvent furnishing the product in 25–
68% yields at 90 °C (entries 7–9). Then, different solvents
such as DMF, MeCN, toluene, DCE, and MeOH were investi-
gated, which afforded 4a in lower yields (entries 10–14).
Among the solvents examined, DMSO exhibited the best
transformation on giving the product 4a in 68% yield (entry
8). Upon conducting the reaction under argon instead of ox-
ygen, the reaction proceeded in 6 hours and the yield de-
creased to 62%. Also the reaction under open air proceeded
in 3 hours and provided 64% yield (entry 15, 16). Next, the
reaction temperature was varied at 80 °C, 100 °C, and
120 °C, resulting in the isolation of the product 4a in 70%
yield at 100 °C (entries 17–19). When the reaction was run
in the absence of CuBr, it afforded 4a in a diminished yield,
while in the absence of KOtBu no reaction product was
formed. Thus, these experiments indicate that copper and
base are pivotal for the reaction (entries 20, 21).
Initially, we embarked on our study by examining the
reaction of 2-amino-N-benzylbenzamide (3a) in the pres-
ence of K2CO3 as the base and Cu(OAc)2 as the catalyst at
With the optimized reaction conditions in hand, the
scope of the reaction was investigated by varying both the
benzylamines and the isatoic anhydride as shown in
Scheme 2. The electronic effect of 2-amino-N-benzylben-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

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S. M. Patel et al.
Paper
Synthesis
Table 1 Optimization of Reaction Conditionsa
O
N
O
O
O
NH2
Cu cat. (15 mol%)
NH
N
H
2
base, solvent
temperature
N
O
NH2
3a
toluene, 100 °C
H
4a
1
Entry
Catalyst
Base
K2CO3
Solvent
Temp (°C)
Yield (%)b
1
2
Cu(OAc)2
CuBr2
CuI
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
90
90
45
49
52
55
50
58
62
68
25
62
60
n.d.
n.d.
n.d.
62c
64d
61
70
60
10
0
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
NaOtBu
KOtBu
NEt3
3
90
4
CuBr
Cu2O
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
–
90
5
90
6
90
7
90
8
90
9
90
10
11
12
13
14
15
16
17
18
19
20
21
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
–
90
MeCN
Toluene
DCE
90
90
90
MeOH
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
90
90
90
80
100
120
100
100
CuBr
a Reaction conditions: 3a (0.22 mmol), base (0.44 mmol), and solvent (1 mL) under O2 for 2 h.
b Isolated yields after column chromatography. n.d. = Not detected.
c Reaction was performed under argon, 6 h.
d Reaction under open air, 3 h.
zamides exerted no obvious influence upon the reaction.
For example, the electron-rich 2-amino-N-benzylben-
zamides showed good reactivity to afford the correspond-
ing quinazolin-4(3H)-ones 4a–d in 62–70% yields. At the
same time, the 2-amino-N-benzylbenzamides with elec-
tron-withdrawing substituents, including F and Cl partici-
pated in the reaction smoothly affording the products 4e–g
in 56–60% yields. The relative sinking product formation
observed for different substituted 2-amino-5-chloro-N-
benzylbenzamide deactivates (3h–3m), is due to the deacti-
vation of the amine nucleophilicity, thereby considerably
decreasing the efficiency of the cyclization reaction (4h–
4m, 45-62%). The structure of the 4b was confirmed by X-
ray crystal structure analysis (Figure 2).
To our delight, 2-amino-N-alkylbenzamide derivatives
synthesized from aliphatic primary amines such as n-pro-
pyl and n-butyl also underwent intramolecular -C–H ami-
nation giving the products 4n and 4o in good yields. In con-
trast, isopropylamine provided the unexpected product 2-
methylquinazolin-4(3H)-one (4p) by C–C bond cleavage.18
Differently, cyclohexylamine afforded the 1′H-spiro[cyclo-
Figure 2 X-ray crystal structure of product 4b. Thermal ellipsoids are
drawn at 30% probability level.17 For details, see the Supporting Infor-
mation.
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S. M. Patel et al.
Paper
Synthesis
O
O
NH2
O
R2
NH
2
CuBr (15 mol%)
O
N
R1
R1
H
KOtBu (2 equiv), O2
N
N
H
O
toluene, 100 °C
NH2
R1
R2
DMSO, 100 °C
4
3
1
R2
O
N
O
O
O
NH OMe
NH
NH
N
NH
N
N
4a, 70%
OMe
4c, 62%
4d, 66%
4b, 65%
O
O
O
O
NH Cl
NH
N
Cl
NH
NH
N
N
N
Cl
F
4g, 56%
4f, 58%
4e, 60%
4h, 62%
O
O
O
O
NH
Cl
Cl
NH
Cl
Cl
NH Cl
NH
N
N
N
N
OMe
F
4i, 58%
4j, 55%
4k, 56%
4l, 58%
O
Cl
NH
N
Cl
4m, 45%
Scheme 2 Scope of isatoic anhydrides and benzylamines. Reagents and conditions: 3 (0.22 mmol), CuBr (15 mol%), KOtBu (2 equiv), DMSO (1 mL), O2,
100 °C.
hexane-1,2′-quinazolin]-4′(3′H)-one (4q ) in good yield un-
der the standard reaction conditions (Scheme 3, 4n–q, 56–
65%).
cross dehydrogenative coupling, C–N bond formation in 4r
and 4s selectively undergoes cyclization only at the benzyl-
ic position in the presence of an N-methyl or N-ethyl moi-
ety. And also, complete selectivity for C–N bond formation
was observed at the benzylic side of tetrahydroisoquinoline
while incorporated the 2-aminobenzamide (4t) and 2-ami-
no-5-chlorobenzamide (4u) (Scheme 4).
O
O
CuBr (15 mol%)
N
R
NH
KOtBu (2 equiv)
H
NH2
DMSO, 100 °C
N
R
After having successful development of copper-cata-
lyzed intramolecular cyclization for the synthesis of
quinazolin-4(3H)-ones 4 from 2-amino-N-alkylbenzamide
derivatives 3, subsequently, we tested the N-methylisatoic
anhydride ring-opened benzylamine product 3 to provide
the 2-arylquinazolinones by N–C bond cleavage along with
the 1-methyl-2-phenylquinazolin-4(1H)-one derivatives
(Scheme 5, 4v–x).
O
N
O
O
O
N
NH
NH
N
NH
NH
N
H
4p, 57%
4o, 60%
4n, 56%
4q, 65%
Scheme 3 Scope of isatoic anhydrides and aliphatic amines
Compared to C–H bond cleavage, N–C bond cleavage has
received much attention in organic chemistry, due to the
inertness of this bond.19 To further rule out the demethyla-
tion, we performed a reaction in different solvents DMF and
MeCN, which provided demethylation product along with
expected product. On the basis of these experimental re-
sults, we propose a reasonable mechanistic pathway. We
have demonstrated a copper-catalyzed approach for the
After the successful synthesis of quinazolin-4(3H)-ones
from isatoic anhydride and primary amines (benzyl and ali-
phatic), attempts to examine the site selectivity aspect of
the ROC strategy were conducted using a number of un-
symmetrical amides 3, which were synthesized from isatoic
anhydride and unsymmetrical secondary amines (Scheme
4). In spite of having two possible N-methylene sites for
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

E
S. M. Patel et al.
Paper
Synthesis
O
N
O
CuBr (15 mol%)
R4
R4
N
N
KOtBu (2 equiv)
R1
R1
NH
DMSO, 100 °C, 4 h
R2
R3
R3
O
3
4
R1, R2 = H
O
N
O
N
O
Cl
N
N
N
N
N
N
4r, 63%
4s, 62%
4t, 58%
4u, 55%
Scheme 4 Scope of isatoic anhydride and unsymmetric benzylamines
O
O
N
N
O
CuBr (15 mol%)
NH
KOtBu (2 equiv)
NH
R2
+
O2, DMSO
100 °C, 4 h
NH
N
R4
R2
R2
4'
4
3
O
N
O
O
O
N
NH
N
N
NH
+
+
N
N
4v', 38%
4v, 34%
4w', 30%
4w, 32%
O
N
N
O
NH
N
+
F
F
4x', 32%
4x, 29%
Scheme 5 Substrate scope for the CuBr-catalyzed synthesis of quinazolin-4(1H)-ones and quinazolin-4(3H)-ones
synthesis of 2-substituted quinazolinones through an intra-
molecular N–C bond cleavage with air as the oxidant under
basic conditions.
under standard conditions, which provided 2-cyclopropyl-
quinazolin-4(3H)-one (4aa) without formation of any ring-
opened coupling products (Scheme 7).
To probe the mechanism of intramolecular -C–H ami-
nation, preliminary control experiments were conducted
whether the reaction proceeds through a radical pathway.
We performed the standard reaction in the presence of rad-
ical scavengers like 2,2,6,6-tetramethylpiperidine 1-oxyl
(TEMPO), di-tert-butyl peroxide (DTP) and tert-butyl per-
oxybenzoate (TBPB) (Scheme 6), which showed no signifi-
cant decrease in the yield of the product 4a, and also did
not observe any radical trapped intermediates. To further
rule out the radical pathway, we performed a radical clock
experiment on the cyclopropyl-substituted derivative 3aa
O
O
N
standard conditions
NH
H
NH2
3a
N
4a
Radical scavengers
Yield
68%
TEMPO (2 equiv)
DTP (2 equiv)
66%
68%
TBPB (2 equiv)
Scheme 6 Control experiments
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

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S. M. Patel et al.
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Synthesis
Having developed a copper-catalyzed rapid synthesis of
2-substituted quinazolin-4(3H)-ones, this ROC strategy was
applied for the synthesis of our target natural product ru-
taecarpine. Thus, isatoic anhydride (1) was treated with
tryptoline (2y) in DMSO for 2 hours to give the desired
product 3y. The compound 3y on treatment with CuBr and
KOtBu under oxygen at 100 °C afforded rutaecarpine (4y) in
60% yield. This strategy was also applied for the synthesis of
evodiamine but we failed to get the expected product 4z.
On treatment of 3z with CuBr and KOtBu under oxygen
rutaecarpine (4y) was obtained in 35% yield (Scheme 9).
In summary, we have developed a copper-catalyzed in-
tramolecular -C–H amination of C(sp3)–H bond for the
synthesis of quinazolin-4(3H)-one derivatives from com-
O
O
N
standard conditions
N
NH
H
NH2
3aa
4aa, 63%
Scheme 7 Radical clock experiment
On the basis of above results, a tentative ionic reaction
mechanism is proposed as shown in Scheme 8. During the
course of these reactions, an iminium ion is found as the
key intermediate I in this transformation, subsequently the
iminium ion undergoes intramolecular cyclization followed
by oxidation, to furnish the desired product 4a (Scheme 8).
O
O
O
NH2
N
CuBr
O
NH
H
Cu
+
NH2
KOtBu
N
O
NH2
H
I
3a
2a
1a
O
O
CuBr
NH
NH
H
KOtBu
N
H
N
O2
4a
II
Scheme 8 Plausible reaction mechanism for the synthesis of quinazolin-4(3H)-ones 4
O
O
N
O
NH
N
DMSO
100 °C
CuBr
N
O
+
KOtBu
DMSO
100 °C
NH2
N
H
N
H
O
HN
HN
1
2y
3y
4y
O
N
N
O
O
N
HN
NH
N
toluene
evodiamine
CuBr
O
+
100 °C
2 h
KOtBu
DMSO, O2
4z
NH
N
H
O
HN
100 °C
2 h
2y
1b
3z
O
N
N
HN
35% yield
4y
Scheme 9 Synthesis of rutaecarpine
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

G
S. M. Patel et al.
Paper
Synthesis
mercially available isatoic anhydride and primary and sec-
ondary amines. This protocol shows good functional group
tolerance and allows access to a range of 2-alkyl- and spiro-
quinazolin-4(1H)-one derivatives in the progress of ROC
strategy. It is the first general method to construct the po-
tentially useful 2-methylquinazolin-4(3H)-one by copper-
catalyzed intramolecular C–H amination. The synthetic
utility of this strategy was illustrated by the convenient
synthesis of rutaecarpine via ROC strategy.
2-Phenylquinazolin-4(3H)-ones through ROC Strategy in Sequen-
tial One-Pot Reaction; General Procedure 3
To a mixture of isatoic anhydride 1 (0.25 mmol) and benzylamine 2
(0.25 mmol) in a 10 mL Schlenk tube was added DMSO (2 mL), and
the mixture was stirred at 100 °C for 1–2 h and monitored by TLC. To
this reaction mixture was added CuBr (15 mol%) and KOtBu (2 equiv),
and the mixture was stirred at 100 °C for 2–3 h (monitored by TLC)
under an O2 balloon. After the completion of the reaction, the mixture
was cooled, quenched with ice-cold H2O, and extracted with EtOAc
(3 × 10 mL). The combined organic extracts were washed with brine
and dried (anhydrous Na2SO4). The crude extract was purified by fil-
tration through a silica gel (100–200 mesh) column using EtOAc and
hexane (8:2) as eluent to yield the desired quinazolinone product 4.
IR spectra were recorded on an FTIR spectrophotometer. 1H NMR
spectra were recorded on a 400 MHz spectrometer at 295 K in CDCl3;
chemical shifts ( ppm) and coupling constants (Hz) are reported in
2-Phenylquinazolin-4(3H)-one (4a)
White solid; yield: 34 mg (70%); mp 140 ° C.
IR (MIR-ATR): 3396, 1655, 1554, 1469, 995, 823, 762, 682, 616 cm–1
1H NMR (400 MHz, CDCl3):  = 7.59–7.51 (m, 4 H), 7.84–7.81 (m, 2 H),
8.35–8.27 (m, 3 H), 11.81 (br s, 1 H).
13C NMR (100 MHz, CDCl3):  = 163.98, 151.81, 149.54, 134.93,
132.83, 131.67, 129.05, 128.02, 127.46, 126.81, 126.38, 120.84.
HRMS (ESI+): m/z calcd for C14H10N2O [M + H+]: 223.0866; found:
223.0862.
standard fashion with reference to either internal standard TMS (H
=
0.00) or CHCl3 (H = 7.25). 13C NMR spectra were recorded on a 100
MHz spectrometer at r.t. in CDCl3; chemical shifts ( ppm) are report-
ed relative to CHCl3 [C = 77.00 (central line of triplet)]. In the 1H NMR,
standard abbreviations were used to denote the multiplicity. The as-
signments of signals were confirmed by 1H and 13C spectra. High-res-
olution mass spectra (HRMS) were recorded using Q-TOF multimode
source. Melting points were determined on an electrothermal melting
point apparatus and are uncorrected. 2-Amino-N-benzylbenzamides
3 were prepared by using known procedures. MeOH and toluene were
dried over sodium metal and DMSO, MeCN and DCE were dried over
CaH2.
.
2-(4-Methoxyphenyl)quinazolin-4(3H)-one (4b)
White solid; yield: 36 mg (65%); mp 232 °C.
All small scale dry reactions were carried out using standard syringe-
septum technique. Reactions were monitored by TLC on silica gel us-
ing a combination of PE and EtOAc as eluents. Reactions were general-
ly run under an O2 atmosphere. Solvents were distilled prior to use;
PE with a boiling range of 40–60 °C was used.
IR (MIR-ATR): 1679, 1600, 1523, 1479, 1247, 1177, 1030, 834, 764
cm–1
.
1H NMR (400 MHz, CDCl3 + DMSO-d6):  = 3.8 (s, 3 H), 6.93 (d, J = 8.8
Hz, 2 H), 7.35 (td, J = 7.3, 7.3 Hz, 1 H), 7.69–7.63 (m, 2 H), 8.14–8.10
(m, 3 H).
13C NMR (100 MHz, CDCl3 + DMSO-d6):  = 162.16, 161.02, 151.08,
2-Amino-N-benzylbenzamides; 2-Amino-N-benzylbenzamide
148.35, 133.25, 128.41, 126.39, 124.19, 119.90, 112.92, 54.36.
(3a); Typical Procedure 1
HRMS (ESI+): m/z calcd for C15H12N2O2 [M + H+]: 253.0972; found:
253.0972.
Isatoic anhydride (1a; 815 mg, 5 mmol) in toluene was treated with
benzylamine (2a; 547 mg, 5 mmol) at 100 °C for 1–2 h and monitored
by TLC. After completion of the reaction, the mixture was washed
with H2O and extracted with EtOAc. The organic layer was dried (an-
hydrous Na2SO4), concentrated in vacuum under reduced pressure,
and then purified by silica gel column chromatography using EtOAc
and hexane (15:85) as eluent to afford the corresponding product 3a
as a white solid; yield: 1.1 g (98%).19
2-(p-Tolyl)quinazolin-4(3H)-one (4c)
White solid; yield: 32 mg (62%); mp 262 °C.
IR (MIR-ATR): 3741, 1669, 1608, 1550, 1299, 941, 832, 767, 730 cm–1
.
1H NMR (400 MHz, CDCl3):  = 11.75 (br s, 1 H), 8.33 (d, J = 7.8 Hz, 1
H), 8.16 (d, J = 7.3 Hz, 2 H), 7.81–7.79 (m, 2 H), 7.49 (t, J = 7.1, 7.1 Hz, 1
H), 7.37 (d, J = 7.8 Hz, 2 H), 2.46 (s, 3 H).
2-Phenylquinazolin-4(3H)-ones Through ROC Strategy; General
Procedure 2
13C NMR (100 MHz, CDCl3):  = 164.00, 151.86, 149.64, 142.18,
134.84, 129.98, 129.75, 127.9, 127.38, 126.56, 126.36, 120.78, 21.56.
HRMS (ESI+): m/z calcd for C15H12N2O [M + H+]: 237.1022; found:
237.1024.
To a mixture of the respective 2-amino-N-benzylbenzamide 3 (0.2
mmol), CuBr (15 mol%), and KOtBu (0.44 mmol) in a 10 mL Schlenk
tube was added of DMSO (2 mL), and the mixture was stirred at
100 °C for 2–4 h (monitored by TLC) under an O2 balloon. After the
completion of the reaction, the reaction mixture was cooled and was
quenched with ice-cold H2O and extracted with EtOAc (3 × 10 mL).
The combined organic extracts were washed with brine and dried
(anhydrous Na2SO4). The crude extract was purified by filtration
through a silica gel (100–200 mesh) column using hexane and EtOAc
(8:2) as eluent to yield the desired quinazolinone product 4.
2-(2-Methoxyphenyl)quinazolin-4(3H)-one (4d)
White solid; yield: 37 mg (66%); mp 170 °C.
IR (MIR-ATR): 3743, 1676, 1593, 1557, 1474, 1233, 1013, 745 cm–1
.
1H NMR (400 MHz, CDCl3):  = 10.95 (br s, 1 H), 8.51 (dd, J = 7.83, 1.96
Hz, 1 H), 8.19–8.36 (m, 1 H), 7.63–7.83 (m, 2 H), 7.38–7.53 (m, 2 H),
7.11–7.18 (m, 1 H), 7.04 (d, J = 8.31 Hz, 1 H), 4.03 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 161.89, 157.76, 150.77, 149.39,
134.45, 133.17, 131.51, 127.85, 126.45, 126.39, 121.83, 121.18,
119.91, 111.81, 56.14.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

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S. M. Patel et al.
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Synthesis
HRMS (ESI+): m/z calcd for C15H12N2O2 [M + H+]: 253.0972; found:
253.0971.
13C NMR (100 MHz, CDCl3 + DMSO-d6):  = 163.36, 149.49, 134.66,
134.37, 129.32, 129.20, 127.51, 126.11, 126.01, 125.47, 120.86,
114.10, 55.39.
HRMS (ESI+): m/z calcd for C15H11ClN2O2 [M + H+]: 287.0582; found:
2-(4-Fluorophenyl)quinazolin-4(3H)-one (4e)
257.0585.
White solid; yield: 32 mg (60%); mp 260 °C.
IR (MIR-ATR): 3742, 1659, 1620, 1215, 755 cm–1
.
6-Chloro-2-(2-chlorophenyl)quinazolin-4(3H)-one (4j)
1H NMR (400 MHz, CDCl3 + DMSO-d6):  = 12.09 (br s, 1 H), 8.17 (dd,
J = 8.1, 6.1 Hz, 2 H), 7.69–7.67 (m, 2 H), 7.39–7.34 (m, 2 H), 7.14–7.10
(m, 2 H).
White solid; yield: 35 mg (55%); mp 270 °C.
IR (MIR-ATR): 3394, 1678, 995, 824, 763 cm–1
.
13C NMR (100 MHz, CDCl3 + DMSO-d6):  = 163.31, 151.39, 149.13,
1H NMR (400 MHz, CDCl3 + DMSO-d6):  = 8.14–8.12 (m, 2 H), 7.81 (s,
134.39, 130.03, 129.94, 127.60, 126.06, 121.02, 115.78, 115.56.
1 H), 7.65–7.48 (m, 2 H), 7.45–7.43 (m, 2 H).
HRMS (ESI+): m/z calcd for C14H9FN2O [M + H+]: 241.0772; found:
13C NMR (100 MHz, CDCl3 + DMSO-d6):  = 160.57, 151.46, 146.38,
241.0777.
133.15, 131.37, 130.07, 128.17, 127.23, 126.52, 123.90, 121.00.
HRMS (ESI+): m/z calcd for C16H8Cl2N2O [M + H+]: 291.0086; found:
291.0076.
2-(2-Chlorophenyl)quinazolin-4(3H)-one (4f)
White solid; yield: 33 mg (58%); mp 155 °C.
6-Chloro-2-(4-fluorophenyl)quinazolin-4(3H)-one (4k)
White solid; yield: 34 mg (56%); mp 260 °C.
IR (MIR-ATR): 3743, 1666, 1605, 1559, 1512, 1474, 1334, 1292, 768,
690 cm–1
.
1H NMR (400 MHz, CDCl3):  = 11.87 (br s, 1 H), 8.35–8.29 (m, 1 H),
8.28–8.27 (m, 2 H), 7.85–7.81 (m, 2 H), 7.61–7.59 (m, 2 H), 7.53–7.49
(m, 1 H).
13C NMR (100 MHz, CDCl3):  = 163.99, 151.79, 149.55, 134.92,
132.83, 131.66, 129.05, 128.02, 127.46, 126.80, 126.37, 120.85.
IR (MIR-ATR): 3419, 1655, 1506, 1420, 1288, 1182, 1023, 994, 825,
730 cm–1
.
1H NMR (400 MHz, CDCl3 + DMSO-d6):  = 12.64 (br s, 1 H), 8.23 (dd,
J = 8.6, 5.1 Hz, 2 H), 8.08–8.05 (m, 1 H), 7.74–7.67 (m, 2 H), 7.24 (t, J =
8.3, and 8.3 Hz, 2 H).
HRMS (ESI+): m/z calcd for C14H9ClN2O [M + H+]: 257.0476; found:
13C NMR (100 MHz, CDCl3 + DMSO-d6):  = 161.41, 151.55, 147.32,
257.0480.
135.81, 134.34, 130.94, 130.1, 129.31, 128.72, 124.83, 115.45, 115.24.
HRMS (ESI+): m/z calcd for C14H8ClFN2O [M + H+]: 275.0382; found:
275.0382.
2-(4-Chlorophenyl)quinazolin-4(3H)-one (4g)
White solid; yield: 32 mg (56%); mp 200 °C.
6-Chloro-2-(p-tolyl)quinazolin-4(3H)-one (4l)
IR (MIR-ATR): 3742, 1740, 1703, 1641, 1516, 1462, 1515, 1240, 720
cm–1
.
White solid; yield: 37 mg (58%); mp 230 °C.
1H NMR (400 MHz, CDCl3 + DMSO-d6):  = 12.49 (br s, 1 H), 8.25–8.18
IR (MIR-ATR): 2920, 1667, 1600, 1466, 1286, 762 cm–1
.
(m, 3 H), 7.77–7.73 (m, 2 H), 7.53–7.48 (m, 3 H).
13C NMR (100 MHz, CDCl3 + DMSO-d6):  = 167.6, 156.3, 153.8, 141.8,
139.3, 136.6, 134.5, 133.6, 133.5, 132.6, 131.5, 130.9, 126.2.
1H NMR (400 MHz, CDCl3 + DMSO-d6):  = 12.46 (br s, 1 H), 8.20–8.09
(m, 2 H), 7.9 (d, J = 3.4 Hz, 1 H), 7.76–7.73 (m, 2 H), 731 (d, J = 6.8, 2 H),
2.43 (s, 3 H).
HRMS (ESI+): m/z calcd for C14H9ClN2O [M + H+]: 257.0476; found:
13C NMR (100 MHz, CDCl3):  = 160.39, 140.22, 132.97, 129.62,
257.0476.
128.38, 127.76, 126.31, 123.68, 120.75, 19.85.
HRMS (ESI+): m/z calcd for C15H11ClN2O [M + H+]: 271.0633; found:
271.0636.
6-Chloro-2-phenylquinazolin-4(3H)-one (4h)
White solid; yield: 35 mg (62%); mp 230 °C.
IR (MIR-ATR): 3742, 2923, 1680, 1646, 1509, 1467, 1250, 690 cm–1
.
6-Chloro-2-(4-chlorophenyl)quinazolin-4(3H)-one (4m)
White solid; yield: 28 mg (45%); mp 320 °C.
IR (MIR-ATR): 3391, 1659, 1021, 997, 825, 763, 624 cm–1
1H NMR (400 MHz, CDCl3 + DMSO-d6):  = 8.21–8.18 (m, 2 H), 7.74–
7.68 (m, 2 H), 7.55 (br s, 1 H), 7.36 (d, J = 5.9 Hz, 1 H).
.
13C NMR (100 MHz, CDCl3 + DMSO-d6):  = 152.44, 147.35, 134.13,
132.33, 131.17, 131.03, 129.06, 128.44, 128.21, 127.41, 124.91,
121.93.
1H NMR (400 MHz, DMSO-d6):  = 12.77 (br s, 1 H), 8.31–8.13 (m, 2
H), 8.09 (s, 1 H), 7.95–7.82 (m, 1 H), 7.77 (d, J = 8.8 Hz, 1 H), 7.68–7.54
(m, 2 H).
HRMS (ESI+): m/z calcd for C14H9ClN2O [M + H+]: 257.0476, found:
13C NMR (100 MHz, DMSO-d6):  = 176.20, 142.93, 136.49, 134.75,
257.0476.
131.26, 130.95, 129.67, 128.70, 128.62, 128.27, 127.81, 124.86.
HRMS (ESI+): m/z calcd for C14H8Cl2N2O [M + H+]: 291.0086; found:
271.0089.
6-Chloro-2-(4-methoxyphenyl)quinazolin-4(3H)-one (4i)
White solid; yield: 37 mg (58%); mp 145 °C.
IR (MIR-ATR): 3723, 1666, 1603, 1508, 1253, 1177, 1031, 832 cm–1
.
2-Ethylquinazolin-4(3H)-one (4n)
White solid; yield: 22 mg (56%); mp 210 °C.
IR (MIR-ATR): 3841, 1682, 1586, 1420, 1234, 1181, 774, 756, 692 cm–1
1H NMR (400 MHz, CDCl3 + DMSO-d6):  = 11.72 (br s, 1 H), 8.28–8.17
(m, 2 H), 7.76–7.68 (m, 2 H), 7.39 (s, 1 H), 7.03 (dd, J = 8.8, 2.4 Hz, 2 H),
3.89 (s, 1 H).
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

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S. M. Patel et al.
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Synthesis
1H NMR (400 MHz, CDCl3):  = 12.23 (br s, 1 H), 8.30 (dd, J = 8.07, 1.22
Hz, 1 H), 7.60–7.86 (m, 2 H), 7.33–7.60 (m, 1 H), 2.86 (q, J = 7.34 Hz, 2
H), 1.47 (t, J = 7.58 Hz, 3 H).
IR (MIR-ATR): 1673, 1564, 1468, 1378, 1254, 1066, 772, 701 cm–1
1H NMR (400 MHz, CDCl3):  = 8.34 (d, J = 7.34 Hz, 1 H), 7.64–7.94 (m,
2 H), 7.37–7.63 (m, 6 H), 4.04 (d, J = 6.85 Hz, 2 H), 1.22 (t, J = 7.09 Hz, 3
H).
.
13C NMR (100 MHz, CDCl3):  = 164.57, 157.79, 149.53, 134.81,
127.22, 126.36, 126.24, 120.50, 29.17, 11.60.
HRMS (ESI+): m/z calcd for C10H10N2O [M + H+]: 175.0866; found:
175.0865.
13C NMR (100 MHz, CDCl3):  = 16 2.01, 156.20, 147.21, 135.62,
134.29, 129.79, 128.82, 127.67, 127.46, 126.95, 126.71, 121.00, 41.19,
14.12.
HRMS (ESI+): m/z calcd for C16H14N2O [M + H+]: 251.1179; found:
251.1185.
2-Propylquinazolin-4(3H)-one (4o)
White solid; yield: 25 mg (60%); mp 180 °C.
IR (MIR-ATR): 3641, 1686, 1556, 1410, 1209, 1191, 776, 766, 698 cm–1
.
5H-Isoquinolino[1,2-b]quinazolin-8(6H)-one (4t)
White solid; yield: 32 mg (58%); mp 140 °C.
IR (MIR-ATR): 1670, 1558, 1475, 1394, 1335, 1150, 768, 707 cm–1
1H NMR (400 MHz, CDCl3):  = 8.49 (dd, J = 7.82, 1.47 Hz, 1 H), 8.27–
8.39 (m, 1 H), 7.70–7.84 (m, 2 H), 7.38–7.57 (m, 3 H), 7.22–7.34 (m, 1
H), 4.33–4.48 (m, 2 H), 3.11 (t, J = 6.60 Hz, 2 H).
1H NMR (400 MHz, CDCl3):  = 12.24 (br s, 1 H), 8.30 (dd, J = 8.07, 1.22
Hz, 1 H), 7.59–7.87 (m, 2 H), 7.39–7.56 (m, 1 H), 2.66–2.88 (m, 2 H),
1.94 (dq, J = 15.10, 7.52 Hz, 2 H), 1.09 (t, J = 7.34 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 164.53, 156.89, 149.53, 134.79,
127.22, 126.21, 120.48, 37.74, 21.05, 13.77.
.
HRMS (ESI+): m/z calcd for C11H12N2O [M + H+]: 189.1022; found:
189.1022.
13C NMR (100 MHz, CDCl3):  = 161.74, 149.40, 147.84, 137.07,
134.23, 131.73, 129.6, 128.05, 127.65, 127.63, 127.51, 126.88, 126.54,
120.78, 39.63, 27.49.
HRMS (ESI+): m/z calcd for C16H12N2O [M + H+]: 249.1022; found:
2-Methylquinazolin-4(3H)-one (4p)
249.1028.
White solid; yield: 20 mg (57%); mp 280 °C.
IR (MIR-ATR): 3346, 1586, 1456, 1310, 1109, 991, 778, 798, 688 cm–1
.
10-Chloro-5H-isoquinolino[1,2-b]quinazolin-8(6H)-one (4u)
White solid; yield: 34 mg (55%); mp 172 °C.
1H NMR (400 MHz, DMSO-d6):  = 12.21 (br s, 1 H), 7.99–8.16 (m, 1
H), 7.72–7.85 (m, 1 H), 7.48–7.60 (m, 1 H), 7.44 (t, J = 7.58 Hz, 1 H),
3.42 (s, 3 H).
13C NMR (100 MHz, DMSO-d6):  = 161.71, 154.24, 145.36, 134.27,
126.7, 125.8, 125.63, 120.56, 21.39.
IR (MIR-ATR): 1672, 1555, 1466, 1394, 1335, 1240, 1153, 1067, 895,
833, 772 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.46 (d, J = 7.34 Hz, 1 H), 8.27 (d, J =
1.96 Hz, 1 H), 7.61–7.81 (m, 2 H), 7.39–7.56 (m, 2 H), 7.19–7.35 (m, 1
H), 4.32–4.52 (m, 2 H), 3.11 (t, J = 6.60 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 160.75, 149.63, 146.33, 137.03,
134.70, 132.21, 131.98, 129.27, 128.05, 127.72, 127.59, 126.22,
121.70, 39.77, 27.36.
HRMS (ESI+): m/z calcd for C9H8N2O [M + H+]: 161.0709; found:
161.0709.
1′H-Spiro[cyclohexane-1,2′-quinazolin]-4′(3′H)-one (4q)
White solid; yield: 31 mg (65%); mp 140 °C.
HRMS (ESI+): m/z calcd for C16H11ClN2O [M + H+]: 283.0633; found:
283.0633.
IR (MIR-ATR): 3324, 3040, 1679, 1580, 1486, 1392, 1182, 1120, 982,
776, 723, 685 cm–1
.
1H NMR (400 MHz, CDCl3):  = 11.29 (br s, 1 H), 8.28 (dd, J = 1.2, 8.1
Hz, 1 H), 7.86–7.60 (m, 2 H), 7.58–7.36 (m, 1 H), 2.83–2.71 (m, 2 H),
2.28–2.10 (m, 1 H), 2.10–1.93 (m, 1 H), 1.91–1.78 (m, 3 H), 1.01–0.84
(m, 3 H).
13C NMR (100 MHz, CDCl3):  = 163.86, 156.74, 134.81, 127.22,
126.40, 126.26, 36.01, 31.38, 27.22, 22.35, 13.94.
1-Methyl-2-phenylquinazolin-4(1H)-one (4v)
Brown solid; yield: 18 mg (34%); mp 210 °C.
IR (MIR-ATR): 1640, 1602, 1519, 1458, 1393, 1257, 1144, 1071, 1036,
765, 699 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.42 (dd, J = 7.82, 1.47 Hz, 1 H), 7.73–
7.88 (m, 1 H), 7.59–7.69 (m, 2 H), 7.44–7.59 (m, 5 H), 3.73 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 168.79, 162.49, 141.82, 134.76,
HRMS (ESI+): m/z calcd for C13H16N2O [M + H+]: 217.1335; found:
217.1328.
133.94, 130.73, 128.88, 128.74, 128.65, 126.27, 120.41, 115.20, 37.98.
HRMS (ESI+): m/z calcd for C15H12N2O [M + H+]: 237.1022; found:
3-Methyl-2-phenylquinazolin-4(3H)-one (4r)
237.1027.
White solid; yield: 33 mg (63%); mp 132 °C.
IR (MIR-ATR): 1673, 1562, 1472, 1352, 1023, 773, 641 cm–1
1H NMR (400 MHz, CDCl3):  = 8.33 (d, J = 8.31 Hz, 1 H), 7.71–7.81 (m,
2 H), 7.45–7.61 (m, 6 H), 3.50 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 162.73, 156.14, 147.33, 135.42,
.
2-Phenylquinazolin-4(3H)-one (4v′)
White solid; yield: 19 mg (38%); mp 142 °C.
IR (MIR-ATR): 3396, 1655, 1554, 1469, 995, 823, 762, 682, 616 cm–1
1H NMR (400 MHz, DMSO-d6):  = 12.56 (br s, 1 H), 8.10–8.25 (m, 3
.
134.32, 130.08, 128.90, 127.51, 127.01, 126.69, 120.54, 34.28.
H), 7.80–7.89 (m, 1 H), 7.70–7.80 (m, 1 H), 7.37–7.62 (m, 4 H).
13C NMR (100 MHz, DMSO-d6):  = 162.21, 152.26, 148.70, 134.57,
HRMS (ESI+): m/z calcd for C15H12N2O [M + H+]: 237.1022; found:
237.1030.
132.67, 131.36, 128.57, 127.73, 127.47, 126.55, 125.82, 120.94.
HRMS (ESI+): m/z calcd for C14H10N2O [M + H+]: 223.0866, found:
3-Ethyl-2-phenylquinazolin-4(3H)-one (4s)
223.0862.
White solid; yield: 34 mg (62%); mp 125 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

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S. M. Patel et al.
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Synthesis
1-Methyl-2-(p-tolyl)quinazolin-4(1H)-one (4w)
13C NMR (100 MHz, CDCl3):  = 135.66, 132.74, 127.57, 121.47,
119.37, 117.86, 110.70, 108.66, 43.86, 43.16, 22.45.
HRMS (ESI+): m/z calcd for C11H12N2 [M + H+]: 173.1073; found:
173.1073.
Yellow solid; yield: 18 mg (32%); mp 165 °C.
IR (MIR-ATR): 1688, 1619, 1514, 1464, 1418, 1286, 1041, 967, 785,
674 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.38 (d, J = 7.82 Hz, 1 H), 7.66–7.85 (m,
1 H), 7.43–7.60 (m, 5 H), 7.21–7.36 (m, 2 H), 3.73 (s, 3 H), 2.43 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 168.87, 162.60, 141.93, 141.15,
133.81, 131.85, 129.22, 129.03, 128.59, 126.08, 120.36, 115.24, 38.12,
21.50.
7,8-Dihydroindolo[2′,3′:3,4]pyrido[2,1-b]quinazolin-5(13H)-one
(4y; Rutaecarpine)
White solid; yield: 38 mg (60%); mp 136 °C.
IR (MIR-ATR): 1613, 1590, 1469, 1435, 1307, 1234, 1159, 736, 698
cm–1
.
HRMS (ESI+): m/z calcd for C16H14N2O [M + H+]: 251.1179; found:
251.1178.
1H NMR (400 MHz, CDCl3):  = 9.95 (br s, 1 H), 8.33 (dd, J = 8.07, 1.22
Hz, 1 H), 7.54–7.83 (m, 3 H), 7.41 (ddd, J = 8.19, 6.72, 1.71 Hz, 1 H),
7.26 (dd, J = 5.14, 1.71 Hz, 2 H), 7.15 (ddd, J = 8.07, 4.65, 3.42 Hz, 1 H),
4.51–4.68 (m, 2 H), 3.22 (t, J = 6.85 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 161.63, 147.41, 145.20, 138.38,
134.42, 127.29, 127.12, 126.49, 126.26, 125.57, 121.15, 120.59,
120.08, 118.49, 112.16, 41.18, 19.68.
2-(p-Tolyl)quinazolin-4(3H)-one (4w′)
White solid; yield: 16 mg (30%); mp 150 °C.
IR (MIR-ATR): 3742, 1672, 1605, 1556, 1473, 1294, 767, 686 cm–1
.
1H NMR (400 MHz, CDCl3):  = 11.68 (br s, 1 H), 8.22–8.43 (m, 1 H),
8.16 (m, J = 8.31 Hz, 2 H), 7.76–7.85 (m, 2 H), 7.49 (ddd, J = 7.95, 6.24,
1.96 Hz, 1 H), 7.37 (m, J = 7.83 Hz, 2 H), 2.46 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 163.96, 151.83, 149.66, 142.18,
134.83, 130.00, 129.75, 128.07, 127.91, 127.36, 126.55, 126.37,
120.79, 21.55.
HRMS (ESI+): m/z calcd for C18H13N3O [M + H+]: 288.1131; found:
288.1136.
2-Cyclopropylquinazolin-4(3H)-one (4aa)
White solid; yield: 26 mg (63%); mp 230 °C.
HRMS (ESI+): m/z calcd for C15H12N2O [M + H+]: 237.1022; found:
237.1026.
IR (MIR-ATR): 2922, 2057, 1669, 1604, 1459, 1395, 981, 893, 763, 606
cm–1
.
1H NMR (400 MHz, CDCl3):  = 11.66 (br s, 1 H), 8.26 (d, J = 7.8 Hz, 1
H), 7.72 (t, J = 7.3, 7.3 Hz, 1 H), 7.6 (d, J = 8.3 Hz, 1 H), 2.03–1.92 (m, 1
H), 1.36–1.28 (m, 2 H), 1.16–1.1 (m, 2 H).
13C NMR (100 MHz, CDCl3):  = 163.97, 157.96, 149.82, 134.65,
127.01, 126.28, 125.66, 120.5, 34.01, 14.72, 9.62.
2-(4-Fluorophenyl)-1-methylquinazolin-4(1H)-one (4x)
White solid; yield: 16 mg (29%); mp 210 °C.
IR (MIR-ATR): 1640, 1493, 1455, 1394, 1225, 1147, 856, 766, 695 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.33 (dd, J = 7.82, 1.47 Hz, 1 H), 7.76
(ddd, J = 8.44, 7.21, 1.47 Hz, 1 H), 7.61–7.69 (m, 2 H), 7.42–7.53 (m, 2
H), 7.12–7.21 (m, 2 H), 3.72 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 168.65, 165.28, 161.47, 141.79,
133.97, 131.35, 131.27, 130.85, 128.59, 126.32, 120.33, 115.95,
115.73, 115.29, 38.08.
Anal. Calcd for C11H10N2O (186.0793): C, 70.95; H, 5.41; N, 15.04.
Found: C, 70.45; H, 5.62; N, 15.48.
Funding Information
HRMS (ESI+): m/z calcd for C15H11FN2O [M + H+]: 255.0928; found:
We gratefully acknowledge the Council of Scientific and Industrial Re-
search (CSIR 02(0297)/17/EMR-II), New Delhi, India and the Indian In-
stitute of Technology Hyderabad (IITH) for financial support. S.M.P.
thanks UGC and S.B. thanks CSIR, New Delhi, India for the award of a
research fellowship.()
255.0921.
2-(4-Fluorophenyl)quinazolin-4(3H)-one (4x′)
White solid; yield: 17 mg (32%); mp 260 °C.
IR (MIR-ATR): 3742, 1659, 1620, 1215, 755 cm–1
.
1H NMR (400 MHz, CDCl3 + DMSO-d6):  = 12.09 (br s, 1 H), 8.17 (dd,
J = 8.1, 6.1 Hz, 2 H), 7.69–7.67 (m, 2 H), 7.39–7.34 (m, 2 H), 7.14–7.10
(m, 2 H).
13C NMR (100 MHz, CDCl3 + DMSO-d6):  = 163.31, 151.39, 149.13,
134.39, 130.03, 129.94, 127.60, 126.06, 121.02, 115.78, 115.56.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611484.
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HRMS (ESI+): m/z calcd for C14H9FN2O [M + H+]: 241.0772; found:
241.0777.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

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