A Facile Microwave and SnCl2Synthesis of 2,3-Dihydroquinazolin-4(1 H)-ones

Article abstract of DOI:10.1071/CH20101

An elegantly simple, facile, and robust approach to a scaffold of biological importance, 2,3-dihydroquinazolin-4(1H)-ones, is reported. A catalytic 1 % SnCl2/microwave-mediated approach afforded access to pure material, collected by cooling and filtration after 20-min microwave irradiation at 120°C. A total of 41 analogues were prepared in isolated yields of 17-99 %. This process was highly tolerant of aliphatic, aromatic, heterocyclic, and acyclic aldehydes, but furan, pyrrole, and thiophene aldehyde reactivity correlated with propensity towards electrophilic addition and/or Diels-Alder addition. As a result, thiophene afforded high yields (80 %) whereas pyrrole carboxaldehyde failed to react. With simple cinnamaldehydes, and in the SbCl3-mediated reaction, and with α,β-unsaturated aldehydes the equivalent quinazolin-4(3H)-ones, and not the 2,3-dihydroquinazolin-4(1H)-ones, was favoured.

Full text of DOI:10.1071/CH20101

RESEARCH FRONT
CSIRO PUBLISHING
Aust. J. Chem.
Full Paper
https://doi.org/10.1071/CH20101
A Facile Microwave and SnCl2 Synthesis of
2,3-Dihydroquinazolin-4(1H)-ones
A
A B
,
Nicholas S. O’Brien and Adam McCluskey
A
Chemistry, School of Environmental and Life Sciences, The University of Newcastle,
University Drive, Callaghan, NSW 2308, Australia.
B
Corresponding author. Email: adam.mccluskey@newcastle.edu.au
An elegantly simple, facile, and robust approach to a scaffold of biological importance, 2,3-dihydroquinazolin-4(1H)-
ones, is reported. A catalytic 1 % SnCl2/microwave-mediated approach afforded access to pure material, collected by
cooling and filtration after 20-min microwave irradiation at 1208C. A total of 41 analogues were prepared in isolated yields
of 17–99 %. This process was highly tolerant of aliphatic, aromatic, heterocyclic, and acyclic aldehydes, but furan, pyrrole,
and thiophene aldehyde reactivity correlated with propensity towards electrophilic addition and/or Diels–Alder addition.
As a result, thiophene afforded high yields (80 %) whereas pyrrole carboxaldehyde failed to react. With simple
cinnamaldehydes, and in the SbCl3-mediated reaction, and with a,b-unsaturated aldehydes the equivalent quinazolin-
4(3H)-ones, and not the 2,3-dihydroquinazolin-4(1H)-ones, was favoured.
Manuscript received: 25 March 2020.
Manuscript accepted: 6 July 2020.
Published online: 24 September 2020.
Introduction
2,3-Dihydroquinazolinones are present in a range of thera-
peutic compounds spanning compound 1 (anticancer),[11] fen-
quizone 2 (diuretic),[12] aquamox 3 (antihypertensive),[13]
Our team over the past two decades has sought to develop
expedient routes to biologically active compounds. In this
regard, our interests span the dynamin and clathrin inhibi-
tors,[1–4] protein phosphatase inhibitors,[5,6] and, most recently,
compounds that hijack the aryl hydrocarbon receptor pathways
as potential breast cancer drugs.[7,8] As part of a current pro-
gram, we sought access to a series of substituted 2,3-
dihydroquinazolinones.[9,10]
evodiamine
4 5 (analgesic and anti-
(anti-obesity),[14]
inflammatory),[15] compound 6 (antileishmanial),[16] and NCI
(National Cancer Institute, USA) substance T1D19143 7
(anticancer)[17] (Fig. 1). The diversity of their biological actions
has meant that there have been multiple synthetic routes devel-
oped to afford rapid access. Among these are the use of metal
o
O
O
O
O
O
O
S
CI
S
NH
NH
H2N
CI
NH
H2N
OCH3
N
H
N
H
N
H
CI
3
2
1
O
O
O
S
N
H2N
N
CI
O
HN
4
O
N
O
O
S
NH
H2N
N
O
NH
N
H
CI
N
H
N
N
N
N
H
N
H
N
6
7
5
Fig. 1. Example 2,3-dihydroquinazolines with known biological activity. Compound 1 (anticancer), fenquizone 2 (diuretic),
aquamox 3 (antihypertensive), evodiamine 4 (anti-obesity), compound 5 (analgesic and anti-inflammatory), compound 6
(antileishmanial) and NCI substance T1D19143 7 (anticancer).
Journal compilation ꢀ CSIRO 2020
www.publish.csiro.au/journals/ajc

B
N. S. O’Brien and A. McCluskey
catalysts, Ga(OTf)3,[18] nano-In2O3,[19] CuO nanoparticles;[20]
protocol to several benzaldehydes (9a–9f); these data are pre-
sented in Table 1.
organic
catalysts:
thiamine
hydrochloride,[21]
2-
morpholinosulfonic acid,[22] b-cyclodextrin-SO3H,[23] ionic
liquids;[24] and other approaches such as magnetic nanoparti-
cles[25] and Amberlyst-15.[26]
As can be determined from analysis of the data presented in
Table 1, these reactions occur efficiently. With electron-
withdrawing and electron-donating benzaldehydes, yields of
,90 % and 40–60 % respectively were routinely obtained. Cited
yields are an average of three experiments in our efforts to
demonstrate reaction variability and reproducibility.[32]
Liquid chromatography–mass spectrometry (LCMS) analy-
sis of the lower-yielding reactions (Supplementary Material),
i.e. those with electron-donating substituents, revealed the
presence of the corresponding 2-phenylquinazolin-4(3H)-one.
With cinnamaldehyde, the quinazolin-4(3H)-one was isolable in
31 % yield (Scheme 2).
The development of a microwave method, a green catalytic
approach that affords the desired analogues in good to high
yields with a simple workup, is presented herein.
Results and Discussion
Access to the quinazolinones has been obtained with multiple
metal catalysts, with several teams proposing numerous reasons
for enhancing the green nature of this reaction,[18–20] be it
through the use of more benign metals or in some instances using
metal-free conditions.[21–26] The use of a microwave and cata-
lytic procedure was explored. With our prior experience with
tin,[27–31] we initially explored the simple microwave coupling
of 2-aminobenzamide (8) with benzaldehyde (9a) in the pres-
ence of 1 % SnCl2 (Scheme 1).
In a typical experiment, 2-aminobenzamide (8) (1 equiv.)
was added to a microwave vial containing benzaldehyde (9a)
(1.05 equiv.), ethanol (3 mL), and 1 mol-% SnCl2. The resulting
suspension was irradiated at 1208C for 20 min. With the parent
benzaldehyde, the product (10a) was collected by filtration in
56 % yield. Inductively coupled plasma (ICP) analysis of the
isolated product showed tin concentrations between 4 and
5 ppm. With this simple successful outcome, we extended this
The effect of solvent, shown in Table 2, was examined with
the model reaction of 8 and 9a as for Scheme 1.
We note from examination of a variety of solvents, with a
bias towards the more environmentally friendly, (data presented
in Table 2) that both EtOH and H2O afforded high yield, by
precipitation, of the desired 10a. Acetonitrile with SnCl2 gave a
poor yield. In the absence of SnCl2, good yields were observed;
noteworthy was the increase in yield with acetonitrile to 87 %. In
the SnCl2-free examples, however, the reaction workup was
significantly more protracted, with 48 h typically required for
product precipitation. With SnCl2, precipitation was evident at
the conclusion of each reaction, rendering this approach more
expedient. Increasing SnCl2 concentration to 10 mol-% allowed
quantitative conversion; however, we viewed this as an unnec-
essary increase in catalyst loading when the 1 % SnCl2 reaction
already afforded high isolated yield. In this sequence of reac-
tions, we also preferred the use of EtOH, as from a practical
standpoint, it ensured that the isolated analogues were easier to
obtain dry. These reactions also proceeded under solvent-free
microwave conditions, but typically afforded an intractable
‘glassy’ solid (data not shown). This approach was not explored
further.
O
O
NH
O
i
+
NH2
NH2
N
H
R
R
8
9
10
Given the successful outcome of the SnCl2 catalytic
approach, we sought to examine an alternative Lewis acid
Scheme 1. Reagents and conditions: (i) SnCl2 (1 %), EtOH, 1208C,
microwave.
Table 1. The reaction of 2-aminobenzamide (8) with benzaldehydes 9a–9f with SnCl2 under microwave irradiation (isolated yields are given)
O
O
O
O
NH
NH
R
R
N
H
N
H
R
R
Reagent, R
Product, yield [ %]
Reagent, R
Product, yield [ %]
9a, H
10a, 56–80
10b, 40–94
10c, 85–95
10d, 40–67
9e, 4-COOH
9f, 4-CH3
10e, 75–96
10f, 40–60
9b, 4-Br
9c, 4-NO2
9d, 4-OH
O
O
N
O
O
O
NH
NH
NH2
NH2
i
i
N
H
Scheme 2. Reagents and conditions: (i) SnCl2 (1 %), EtOH, 1208C, microwave.

Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones
C
catalyst, and with SbCl3 examined the reaction of 8 and 9a as
with SnCl2 (Table 3 and Scheme 3).
yields. Heteroaromatic aldehydes were tolerated (10u and 10v),
as were small saturated rings (10w and 10x), simple cyclic
olefins (10y) and aliphatic chains (10z and 10aa). Steric bulk
affected yields, with the less encumbered 2-naphthyl 10ac
isolated in 56 %, a greater yield than the equivalent 1-naphthyl
10ab. This was also noted with the bulky cinnamaldehyde 9ae,
which failed to react. With the five-ring heterocycles furan (9af–
9ah), pyrrole (9i), and thiophene (9aj), the reaction outcomes
aligned with the propensity of the aromatic nucleus to partici-
pate in electrophilic and Diels–Alder chemistry. Thus, simple
furans failed to react (9af and 9ag), but introducing a bulky
electron-withdrawing moiety (9ah; Br) afforded a modest yield
of the desired analogue, 10ah. Pyrrole carboxaldehyde (9ai)
failed to react, whereas thiophene carboxaldehyde (9aj) gave
80 % of the isolated product 10aj (Table 5).
In a final investigation, the effect of aldehyde conjugation on
the SnCl2/microwave-mediated coupling was examined. Anal-
ysis of the data presented in Table 6 shows that, in most cases,
the anticipated 2,3-dihydroquinazolin-4(1H)-one scaffold was
isolated in modest to good yields, although two indole carbox-
aldehydes (9an and 9ar) failed to react. Of greater interest was
the switch in product outcome on the introduction of simple
The SbCl3-mediated reaction typically afforded an undesir-
able and difficult to separate mixture of the desired 2,3-dihy-
droquinazolin-4(1H)-ones and the parent quinazolinon-4(3H)-
ones. This was evident across the catalyst loadings and solvent
systems examined. We do note, though, that essentially quanti-
tative conversion to 2-phenylquinazolon-4(3H)-one 11a was
feasible by heating at reflux in THF. We presume that this may
be a consequence of initial formation of the 2,3-dihydro ana-
logue (10) followed by oxidation in the open flask. This
oxidation step has previously been observed with analogues of
this nature.[33] In our hands, a KMnO4-mediated oxidation of the
2,3-dihydro analogues gave the equivalent quinazolin4(3H)-
ones, but this was not the focus of the present work (data not
shown).
Having established that the microwave/SnCl2 approach was
an expedient route to the desired 2,3-dihydroquinazolon-4(1H)-
ones, we expanded the scope of our investigations to include
more interesting aldehydes and ketones and the outcomes of
these studies are presented in Table 4.
High tolerances were observed during the SnCl2/microwave
coupling of a range of aldehydes, shown in Table 4, which
proceeded smoothly. This was especially evident with electron-
withdrawing substituents, e.g. 3-Br 9h, 2-NO2 9j, 4-CN 9m,
affording .85 % isolated yields. Those possessing electron-
donating substituents, 3-OCH3 9q, gave low yields (Table 4). As
medicinal chemistry requires access to a robust and reliable
toolkit, we continued to explore the scope of this coupling,[34,35]
introducing several variations of the aldehyde moiety.
Analysis of the data presented in Table 5 reveals similar
trends to those noted above; electron-withdrawing substituent
result in high yields, and electron-donating substituents, low
O
O
NH
O
i
+
NH2
NH2
N
R
R
8
9a
11a
Scheme 3. Reagents and conditions: (i) SbCl3 (1–3 %), microwave or
reflux.
Table 2. Effect of solvent on the synthesis of 2-phenyl-2,3-dihydroquinazolin-4(1H)-one from 2-aminobenzamide (8) and benzaldehyde (9a)
Solvent
SnCl2
Yield
PurityA
EtOH
MeCN
H2O
1 % equiv.
80 %
50 %
86 %
61 %
87 %B
65 %B
96 %
61 %
.99 %
,45 %
,35 %
.96 %
.99 %
.99 %
.99 %
.99 %
1 % equiv.
1 % equiv.
EtOH
MeCN
H2O
–
–
–
10 %
EtOH
EtOH
1 mol-%/0.4 equiv. K2CO3
APurity of isolated product as determined by 1H NMR.
BProduct isolated via slow crystallisation at room temperature over 2 days. No product afforded after addition of H2O.
Table 3. The reaction of 2-aminobenzamide (8) with benzaldehyde (9a) and SbCl3
Reaction conditions as stated below; isolated yields are given
Solvent
Catalyst [mol-%]
Heating type
Result
Purity
EtOH
MeCN
MeCN
–
1 %
1 %
3 %
3 %
3 %
3 %
MicrowaveA
2,3-dihydroquinazolinone
2,3-dihydroquinazolinone
2,3-dihydroquinazolinone
2,3-dihydroquinazolinone
2,3-dihydroquinazolinone
4(3H)-quinazolinone
.98 %
75 %
Microwave (1208C, 20 min)
Microwave (1208C, 20 min)
Microwave (1208C, 20 min)
Microwave (1408C, 30 min)
Reflux overnight
90 %
,50 %
,50 %
.98 %
–
THF
AReaction occurred and product precipitated before 1208C was reached.

D
N. S. O’Brien and A. McCluskey
Table 4. The reaction of 2-aminobenzamide (8) with benzaldehydes 9g–9s with SnCl2 under microwave irradiation conditions (isolated yields
are given)
O
O
O
O
NH
NH
R
R
N
H
N
H
R
R
Reagent
R
Product
Yield [ %]
Reagent
R
Product
Yield [ %]
9g
9h
9i
2-Br
3-Br
10g
10h
10i
40
99
29
90
78
72
86
9n
9o
9p
9q
9r
9s
2-COOH
3-COOH
4-Ph
10n
10o
10p
10q
10r
10s
58
86
75
17
67
45
3-CF3
2-NO2
3-NO2
3-CN
4-CN
9j
10j
3-OCH3
3-OH
9k
9l
10k
10l
3,4,5-tri-OH
9m
10m
Table 5. The reaction of 2-aminobenzamide (8) with aldehydes 9t–9aj with SnCl2 under microwave irradiation conditions (isolated yields are given)
Reagent
O
Product
Yield [ %]
Reagent
O
Product
Yield [ %]
NH
NH
N
H
R
N
H
R
9t
10t
39
48
9ac
9ad
10ac
10ad
86
0
N
N
9u
10u
Ph
S
Ph
Br
9v
10v
71
9ae
10ae
40
Ph
O
O
O
9w
9x
10w
10x
87
89
9af
10af
10ag
0
0
9ag
O
9y
9z
10y
10z
92
34
9ah
9ai
10ah
10ai
25
0
Br
H
N
S
9aa
9ab
10aa
10ab
34
30
9aj
10aj
80
cinnamaldehydes (9as–9au) and hepten-2-al (9av) affording the
conjugated quinazolin-4(3H)-ones 11a–11d.
approach afforded essentially pure material, collected by cool-
ing and filtration after 20-min microwave irradiation at 1208C.
Electron-withdrawing substituents on the aldehyde moiety gave
higher yields, often .85 %, with good batch-to-batch repro-
ducibility. Electron-donating substituents afforded lower yields,
but in a medicinal chemistry campaign, acceptable to enable any
required screening.
Conclusions
A facile and robust access to 2,3-dihydroquinazolin-4(1H)-ones
was achieved. A catalytic 1 % SnCl2/microwave-mediated

Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones
E
Table 6. The reaction of 2-aminobenzamide (8) with conjugated aldehydes 9ak–9as (isolated yields are given)
Reagent
O
Product
Yield [ %]
Reagent
O
Product
Yield [ %]
NH
NH
N
H
R
N
H
R
N
NO2
9ak
9al
10ak
10al
59
28
9ao
9ap
10ao
10ap
0
O
53
N
H
9am
9an
10am
10an
17
0
9aq
9ar
10aq
10ar
35
0
CN
N
H
N
H
Br
N
H
N
H
Reagent
O
N
Product
Yield [ %]
Reagent
O
N
Product
Yield [ %]
NH
NH
9ap
9aq
11a
11b
54
37
9ar
9as
11c
11d
62
24
Br
OMe
This procedure was highly tolerant of aliphatic, aromatic,
heterocyclic, and acyclic aldehydes. With small-ring hetero-
cycles, e.g. furan, pyrrole, and thiophene, there was a correla-
tion between propensity towards electrophilic addition and
Diels–Alder addition. As a result, thiophene afforded high
yields (80 %) whereas pyrrole carboxaldehyde failed to react.
With simple cinnamaldehydes and a,b-unsaturated aldehydes,
a switch occurred towards the corresponding quinazolin-
4(3H)-ones.
LCMS in electrospray ionisation (ESI) positive and negative
modes. TLC was performed on Merck silica gel 60 F254 pre-
coated aluminium plates with a thickness of 0.2 mm. Column
chromatography was performed under flash conditions on
Merck silica gel 60 (230–400 mesh). ICP analysis was per-
formed on an Agilent 5110 Inductively Coupled Plasma Optical
Emission Spectrometry (ICP-OES) instrument.
Nuclear magnetic resonance (NMR) spectroscopy was per-
formed on a Bru¨ker Avance III 400 MHz spectrometer, where
proton NMR (1H NMR) spectra and carbon NMR (13C NMR)
spectra were acquired at 400 and 100 MHz respectively, or a
Bru¨ker Avance III 600 MHz spectrometer, where proton NMR
(1H NMR) spectra and carbon NMR (13C NMR) spectra were
acquired at 600 and 150 MHz respectively. All spectra were
recorded in deuterated dimethyl sulfoxide ([D6]DMSO), deu-
terated acetone ([D6]acetone) or deuterated chloroform
(CDCl3) obtained from Cambridge Isotope Laboratories Inc.
Chemical shifts (d) are measured in parts per million (ppm) and
referenced against the internal reference peaks. Coupling con-
stants (J) are measured in hertz (Hz). NMR assignments were
determined through the interpretation of one- and two-
dimensional spectra. Multiplicities are denoted as singlet (s),
broad singlet (bs), doublet (d), doublet of doublets (dd), triplet
(t), quartet (q), triplet of doublets (td), doublet of triplets (dt) and
multiplet (m). Peaks are listed in decreasing chemical shift in the
following format: chemical shift (integration (1H), multiplicity
Experimental
General Methods
All reactions were performed using standard laboratory equip-
ment and glassware. HPLC grade solvents and reagents were
purchased from Sigma–Aldrich, Alfa Aesar or AK Scientific
and used as received. Organic solvents were of bulk quality, and
were distilled from glass before use. Organic solvent extracts
were dried with magnesium sulfate (MgSO4), and dried under
reduced pressure with either Bu¨chi or Heidolph rotary eva-
porators. Melting points were recorded in open capillaries on a
Stuart SMP11 melting point apparatus. Where available, liter-
ature values are provided and appropriately referenced. Elec-
trospray mass spectra were recorded using 10 % DMSO/H2O or
HPLC-grade methanol or acetonitrile as carrier solvents on an
Agilent Technologies 1260 Infinity Ultra Performance Liquid
Chromatography (UPLC) system with a 6120 Quadrupole

F
N. S. O’Brien and A. McCluskey
(1H), coupling constant (1H). A Biotageꢁ Initiatorþ was used to
2-(4-Carboxyphenyl)-2,3-dihydroquinazolin-4(1H)-one
(10e)
perform microwave reactions.
Synthesised as for 10a from 8 and 4-formylbenzoic acid (9e) to
afford the title compound 10e as a white solid, 341 mg; 96 %
yield.
2-Phenyl-2,3-dihydroquinazolin-4(1H)-one (10a)
To a microwave vial containing 2-aminobenzamide (8; 226 mg,
1.66 mmol), benzaldehyde (9a; 0.17 mL, 1.73 mmol, 1.1 equiv.)
and tin(II) chloride (3 mg, 0.015 mmol, 0.01 equiv.) were added
and stirred in ethanol (3 mL) to form a suspension. The microwave
vial was then irradiated at 1208C for 20 min. The resultant pre-
cipitate was then collected by filtration and washed with minimal
H2O (or diethyl ether), affording 2-phenyl-2,3-dihydroquinazolin-
4(1H)-one as a white crystalline solid (298 mg, 80 %).
dH (400 MHz, DMSO) 8.27 (s, 1H), 7.61 (dd, J 7.7, 1.6, 1H),
7.49 (dd, J 8.2, 1.3, 2H), 7.43–7.31 (m, 3H), 7.24 (ddd, J 8.2, 7.2,
1.6, 1H), 7.10 (s, 1H), 6.75–6.73 (m, 1H), 6.69–6.65 (m, 1H),
5.75 (s, 1H). dC (101 MHz, DMSO) 163.6, 147.9, 141.6, 133.3,
128.4, 128.3 (2C), 127.3, 126.8 (2C), 117.1, 114.9, 114.4, 66.5.
m/z (LRMS ESIþ) 225 (M þ H, C14H13N2O, 100 %); (ESI–)
223 (M – H C14H11N2O, 100 %). nmax (ATR)/cmꢀ1 3308 (NH),
3169 (NH), 3061 (CH), 1649 (C=O). Mp .2258C (dec.).
dH (400MHz, DMSO) 8.38 (s, 1H), 7.94–7.92 (m, 2H), 7.60
(dd, J 12.0, 4.9, 3H), 7.25 (ddd, J 8.7, 7.3, 1.6, 1H), 7.20 (s, 1H),
6.74 (d, J 7.7, 1H), 6.70–6.68 (m, 1H), 5.82 (s, 1H). dC (101MHz,
DMSO) 167.3, 163.8, 147.7, 146.7, 133.8, 131.0 (2C), 129.6,
127.6, 127.1 (2C), 117.6, 115.0, 114.7, 66.1. nmax (ATR)/cmꢀ1
3289 (NH), 2800 (OH), 1695 (C=O), 725 (C=C). m/z (LRMS
ESIþ) 269.2 (M þ H, C15H13N2O3, 100 %); (ESI–) 267.1 (M-H,
C15H11N2O3, 100 %). Mp .3008C.
2-(p-Tolyl)-2,3-dihydroquinazolin-4(1H)-one (10f)
Synthesised as for 10 from 8 and 4-methylbenzaldehyde (9f) to
afford the title compound 10f as an off-white solid, 141 mg;
60 % yield.
dH (400 MHz, DMSO) 8.22 (s, 1H), 7.60 (dd, J 7.7, 1.4, 1H),
7.36 (d, J 8.0, 2H), 7.23 (ddd, J 8.7, 7.3, 1.6, 1H), 7.18 (d, J 7.9,
2H), 7.04 (s, 1H), 6.73 (d, J 8.1, 1H), 6.68–6.64 (m, 1H), 5.70
(s, 1H), 2.29 (s, 3H). dC (101 MHz, DMSO) 164.1, 148.3, 139.1,
138.2, 133.7, 129.3 (2C), 127.8, 127.2 (2C), 117.54, 115.4,
114.9, 66.8, 21.2. nmax (ATR)/cmꢀ1 3312 (NH), 2918 (CH),
1655 (C=O). m/z (LRMS ESIþ) 239.1 (M þ H, C15H15N2O,
100 %); (LRMS ESI–) 237.2 (M-H, C15H13N2O3, 100 %). Mp
.207.68C.
2-(4-Bromophenyl)-2,3-dihydroquinazolin-4(1H)-one (10b)
Synthesised as for 10a from 8 and 4-bromobenzaldehyde (9b) to
afford the title compound 10b as a white solid, 418 mg; 94 %
yield.
dH (400 MHz, DMSO) 8.32 (s, 1H, NH), 7.61–7.57 (m, 3H),
7.44–7.42 (m, 2H), 7.25 (ddd, J 8.2, 7.2, 1.6, 1H), 7.13 (s, 1H,
NH), 6.74 (dd, J 8.1, 0.5 ,), 6.70–6.66 (m, 1H), 5.75 (s, 1H). dC
(101 MHz, DMSO) 163.5, 147.6, 141.1, 133.4, 131.2 (2C),
2-(2-Bromophenyl)-2,3-dihydroquinazolin-4(1H)-one (10g)
129.1 (2C), 127.4, 121.6, 117.3, 114.9, 114.5, 65.8. m/z
79
Synthesised as for 10a from 8 and 2-bromobenzaldehyde (9g) to
afford the title compound 10g as a white solid, 187 mg; 40 %
yield.
dH (400MHz, DMSO) 8.19 (s, 1H, NH), 7.69–7.64 (m, 3H),
7.45 (td, J 7.5, 1.1, 1H), 7.33(ddd, J 7.9, 7.4, 1.8, 1H), 7.26 (ddd, J
8.2, 7.2, 1.6, 1H), 6.98 (s, 1H, NH, H1), 6.77–6.70 (m, 2H), 6.09
(s, 1H). dC (101MHz, DMSO) 163.6, 147.7, 139.1, 133.4, 132.8,
(LRMS ESIþ) 303 (M þ H, C14H BrN2O, 100 %), 305
12
81
(M þ H, C14H BrN2O, 95 %), 347 (M þ FA-H (FA ¼ formic
12
79
12
81
12
acid), C14H BrN2O, 100 %), 349 (M þ FA-H, C14H BrN2O,
79
95 %); (ESI–) 301 (M-H, C14H BrN2O, 100 %), 303 (M – H,
10
81
10
C14H BrN2O, 95 %). nmax (ATR)/cmꢀ1 (3308, N–H), 1652
(C=O). Mp .1918C (dec.).
130.7, 129.1, 128.1, 127.4, 122.2, 117.5, 114.7, 114.6, 66.4. m/z
79
2-(4-Nitrophenyl)-2,3-dihydroquinazolin-4(1H)-one (10c)
(LRMS ESIþ) 303 (M þ H, C14H BrN2O, 100 %), 305 (Mþ H,
12
81
12
Synthesised as for 10a from 8 and 4-nitrobenzaldehyde (9c) to
afford the title compound 10c as a yellow solid, 425 mg; 95 %
yield.
C14H BrN2O, 95%); (ESI–) 301 (M – H, C14H799BrN2O,
100 %), 303 (M – H, C14H891BrN2O, 95%). nmax (ATR)/cmꢀ1
3365 (NH), 1646 (C=O). Mp .1738C (dec.).
dH (400 MHz, DMSO) 8.51 (s, 1H), 8.25 (d, J 8.8, 2H), 7.74
(d, J 8.7, 2H), 7.62–7.60 (m, 1H), 7.32 (s, 1H), 7.28–7.24
(m, 1H), 6.76 (d, J 8.0, 1H), 6.69 (t, J 7.4, 1H), 5.91 (s, 1H).
dC (101 MHz, DMSO) 163.3, 149.3, 147.2, 133.6, 128.0, 127.4,
123.6, 117.5, 114.9, 114.5, 65.3. nmax (ATR)/cmꢀ1 3279 (NH),
3173 (NH), 3100 (CH), 1644 (C=O). m/z (LRMS ESIþ) 270.1
(M þ H, C14H11N3O3, 100 %); (LRMS ESI–) 268.1 (M – H,
C14H11N3O3, 100 %). Mp .1978C (dec.).
2-(3-Bromophenyl)-2,3-dihydroquinazolin-4(1H)-one (10h)
Synthesised as for 10a from 8 and 3-bromobenzaldehyde (9h) to
afford the title compound 10h as a white solid, 491 mg; 99 %
yield.
dH (400MHz, DMSO) 8.39 (s, 1H), 7.65 (t, J 1.7, 1H), 7.60
(dd, J 7.7, 1.4, 1H), 7.52 (ddd, J 7.9, 1.8, 1.0, 1H), 7.47 (d, J 7.8,
1H), 7.34(t, J 7.8, 1H), 7.25(ddd, J 8.6, 7.3, 1.6, 1H), 7.20(s, 1H),
6.75 (d, J 7.8, 1H), 6.72–6.64 (m, 1H), 5.76 (s, 1H). dC (101MHz,
DMSO) 163.6, 147.5, 144.8, 133.7, 131.3, 130.7, 129.7, 127.5,
125.8, 121.7, 117.5, 114.9, 114.6, 65.5. nmax (ATR)/cmꢀ1 3282
(NH), 3172 (NH), 3062 (CH), 1645 (C=O). m/z (LRMS ESIþ)
303 (Mþ H, C14H1279BrN2O, 100%), 305 (Mþ H,
C14H1281BrN2O, 90%); (ESI–) 301 (M – H, C14H1079BrN2O,
100 %), 303 (M – H, C14H1081BrN2O, 90%). Mp .1748C (dec.).
2-(4-Hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (10d)
Synthesised as for 10a from 8 and 4-hydroxybenzaldehyde (9d)
to afford the title compound 10d as a white solid, 163 mg; 67 %
yield.
dH (400 MHz, DMSO) 9.53 (s, 1H), 8.09 (d, J 4.3, 1H), 7.61
(dd, J 7.7, 1.5, 1H), 7.32–7.29 (m, 2H), 7.24 (ddd, J 8.3, 7.2, 1.6,
1H), 6.94 (s, 1H), 6.79–6.66 (m, 4H), 5.66 (s, 1H). dC (101 MHz,
DMSO) 164.2, 158.1, 148.6, 133.7, 132.1, 128.7 (2C), 127.8,
117.5, 115.4 (2C), 114.8, 67.1. nmax (ATR)/cmꢀ1 3346 (NH),
3175 (NH), 1229 (C=O). m/z (LRMS ESIþ) 241.1 (M þ H,
C14H13N2O2, 100 %); (ESI–) 239.1 (M-H, C14H12N2O2, 100 %).
Mp .2008C.
2-(3-(Trifluoromethylphenyl)-2,3-dihydroquinazolin-
4(1H)-one (10i)
Synthesised as for 10a from 8 and 3-trifluoromethylbenzaldehyde
(9i) to afford the title compound 10i as a white solid, 138 mg;
29 % yield.

Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones
G
dH (400 MHz, DMSO) 8.42 (s, 1H), 7.85 (s, 1H), 7.80 (d, J
7.7, 1H), 7.72 (d, J 7.8, 1H), 7.64–7.610 (m, 2H), 7.29–7.23
(m, 2H), 6.78–6.76 (m, 1H), 6.72–6.68 (m, 1H), 5.89 (s, 1H). dC
(101 MHz, DMSO) 163.5, 147.6, 143.1, 133.5, 131.0, 129.5,
127.4, 125.20, 125.16, 123.64, 123.60, 117.4, 114.9, 114.5,
65.7. nmax (ATR)/cmꢀ1 3275 (NH), 3211 (NH), 1645 (C=O).
m/z (LRMS ESIþ) 293.1 (M þ H, C15H12F3N2O, 100 %);
(LRMS ESI–) 291.1 (M – H, C15H10F3N2O, 100 %). Mp
137–1418C.
(M þ H, C15H12N3O, 100 %); (LRMS ESI–) 248.1 (M – H,
C15H10N3O, 100 %). Mp 240–2478C.
2-(2-Carboxyphenyl)-2,3-dihydroquinazolin-4(1H)-one
(10n)
Synthesised as for 10a from 8 and 2-carboxybenzaldehyde (9n)
to afford the title compound 10n as a yellow solid, 252 mg; 58 %
yield.
dH (400 MHz, DMSO) 9.48 (s, 1H), 8.22 (s, 1H), 7.60 (dd, J
7.7, 1.5, 1H), 7.23 (ddd, J 8.2, 7.2, 1.6, 1H), 7.16 (t, J 7.9, 1H),
7.06 (s, 1H), 6.89 (t, J 4.3, 2H), 6.76–6.69 (m, 2H), 6.69–6.63
(m, 1H), 5.64 (s, 1H). dC (101 MHz, DMSO) 163.5, 157.3,
147.8, 143.2, 133.3, 129.3, 127.3, 117.4, 117.0, 115.3, 114.9,
114.3, 113.7, 66.5, 39.5. nmax (ATR)/cmꢀ1 3282 (NH), 3036
(NH), 1726 (C=O), 1674 (C=O). m/z (LRMS ESIþ) 251.1
(M þ H – H2O, C15H11N2O2, 100 %); (ESI–): 249.1 (M – H –
H2O, C15H9N2O2, 100 %). Mp .2408C (dec.).
2-(2-Nitrophenyl)-2,3-dihydroquinazolin-4(1H)-one (10j)
Synthesised as for 10a from 8 and 2-nitrobenzaldehyde (9j) to
afford the title compound 10j as an orange solid, 414 mg; 90 %
yield.
dH (400 MHz, DMSO) 8.21 (s, 1H), 8.06 (dd, J 8.1, 0.9, 1H),
7.85–7.84 (m, 1H), 7.79 (t, J 7.2, 1H), 7.66–7.61 (m, 2H), 7.28–
7.24 (m, 1H), 7.00 (s, 1H), 6.77 (d, J 8.1, 1H), 6.72 (t, J 7.5, 1H),
6.33 (s, 1H). dC (101 MHz, DMSO) 163.3, 147.7, 147.1, 135.9,
133.9, 133.5, 129.9, 128.9, 127.3, 124.7, 117.7, 114.9, 114.5,
62.2. nmax (ATR)/cmꢀ1 3409 (NH), 3182 (NO), 1654 (C=O). m/z
(LRMS ESIþ) 270.1 (M þ H, C14H11N3O3, 100 %).
Mp .194.68C (dec.).
2-(3-Carboxyphenyl)-2,3-dihydroquinazolin-4(1H)-one
(10o)
Synthesised as for 10a from 8 and 3-carboxybenzaldehyde (9o)
to afford the title compound 10o as a white solid, 398 mg; 86 %
yield.
2-(3-Nitrophenyl)-2,3-dihydroquinazolin-4(1H)-one (10k)
dH (400 MHz, DMSO) 8.38 (s, 1H), 8.08 (s, 1H), 7.90 (dt,
1H), 7.71 (dt, 1H), 7.60 (dd, J 7.8, 1.5, 1H), 7.51 (t, J 9.6, 1H),
7.25 (ddd, J 8.2, 7.2, 1.6, 1H), 7.19 (s, 1H), 6.74 (d, 1H), 6.71–
6.65 (m, 1H), 5.83 (s, 1H). dC (101 MHz, DMSO) 167.4, 163.8,
147.8, 142.5, 133.8, 131.5, 131.1, 129.5, 129.0, 127.9, 127.6,
117.6, 115.0, 114.7, 66.1. nmax (ATR)/cmꢀ1 3334 (NH), 3200
(NH), 1666 (C=O), 750.5 (C=C). m/z (LRMS ESIþ) 269.2
(M þ H, C15H13N2O3, 100 %). Mp .3008C.
Synthesised as for 10a from 8 and 3-nitrobenzaldehyde (9k) to
afford the title compound 10k as a yellow-orange solid, 356 mg;
78 % yield.
dH (400 MHz, DMSO) 8.52 (s, 1H), 8.36 (s, 1H), 8.13–8.19
(m, 1H), 7.94 (d, J 7.7, 1H), 7.70 (t, J 7.9, 1H), 7.62 (d, J 7.3, 1H),
7.34 (s, 1H), 7.27 (t, 1H), 6.79 (d, J 8.1, 1H), 6.70 (t, J 7.4, 1H),
5.95 (s, 1H). dC (101 MHz, DMSO) 163.3, 147.7, 147.3, 144.3,
133.6, 133.4, 130.0, 127.4, 123.3, 121.6, 117.5, 114.9, 114.6,
65.2. nmax (ATR)/cmꢀ1 3289 (NH), 3179 (NH), 3072 (CH),
1650 (C=O). m/z (LRMS ESIþ) 270.1 (M þ H, C14H11N3O3,
100 %); (LRMS ESI–) 268.1 (M – H, C14H11N3O3, 100 %). Mp
.1948C (dec.).
2-([1,10-Biphenyl]-4-yl)-2,3-dihydroquinazolin-4(1H)-one
(10p)
Synthesised as for 10a from 8 and 4b-phenylbenzaldehyde (9p)
to afford the title compound 10p as a white solid, 398 mg; 75 %
yield.
2-(3-Cyanophenyl)-2,3-dihydroquinazolin-4(1H)-one (10l)
dH (400 MHz, DMSO) 8.38 (s, 1H), 8.08 (s, 1H), 7.90 (dt,
1H), 7.71 (dt, 1H), 7.60 (dd, J 7.8, 1.5, 1H), 7.51 (t, J 9.6, 1H),
7.25 (ddd, J 8.2, 7.2, 1.6, 1H), 7.19 (s, 1H), 6.74 (d, 1H), 6.71–
6.65 (m, 1H), 5.83 (s, 1H). dC (101 MHz, DMSO) 167.4, 163.8,
147.8, 142.5, 133.8, 131.5, 131.1, 129.5, 129.0, 127.9, 127.6,
117.6, 115.0, 114.7, 66.1. nmax (ATR)/cmꢀ1 3334 (NH), 3200
(NH), 1666 (C=O), 750.5 (C=C). (LRMS ESI–) 267.1 (M – H,
C15H15N2O3, 100 %), 535.2 (2M – H, C15H15N2O3, 100 %). Mp
.3008C.
Synthesised as for 10a from 8 and 3-cyanobenzaldehyde (9l) to
afford the title compound 10l as a white solid, 308 mg; 72 %
yield.
dH (400 MHz, DMSO) 8.42 (s, 1H), 7.91 (s, 1H), 7.85–7.82
(m, 2H), 7.62 (ddd, J 7.8, 4.6, 3.3, 2H), 7.33–7.20 (m, 2H), 6.77
(d, J 8.0, 1H), 6.73–6.68 (m, 1H), 5.85 (s, 1H). dC (101 MHz,
DMSO) 163.4, 147.5, 143.3, 133.5, 132.2, 131.7, 130.6, 129.7,
127.4, 118.7, 117.5, 115.0, 114.6, 111.2, 65.5. nmax (ATR)/cmꢀ1
3372 (NH), 3178 (NH), 2232 (CN), 1659 (C=O). m/z (LRMS
ESIþ) 250.1 (M þ H, C15H12N3O, 100 %); (LRMS ESI–) 248.1
(M – H, C15H10N3O, 100 %). Mp 224–2308C.
2-(3-Methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one
(10q)
Synthesised as for 10a from 8 and 3-methoxybenzaldehyde (9q)
to afford the title compound 10q as an off-white solid, 72 mg;
17 % yield.
2-(4-Cyanophenyl)-2,3-dihydroquinazolin-4(1H)-one
(10m)
dH (400 MHz, DMSO) 8.29 (s, 1H), 7.61 (dd, J 7.7, 1.5, 1H),
7.30 (t, J 8.1, 1H), 7.28–7.22 (m, 1H), 7.12 (s, 1H), 7.09–7.04
(m, 2H), 6.91 (ddd, J 8.2, 2.5, 0.8, 1H), 6.78–6.74 (m, 1H), 6.70–
6.64 (m, 1H), 5.72 (s, 1H), 3.75 (s, 3H). dC (101 MHz, DMSO)
164.0, 159.7, 148.3, 143.8, 133.8, 129.9, 127.8, 119.4, 117.6,
115.4, 114.90, 114.1, 113.0, 66.5, 55.6. nmax (ATR)/cmꢀ1 3288
(NH), 3053 (NH), 2916 (CH), 1645 (C=O). m/z (LRMS ESIþ)
255.1 (M þ H, C15H15N2O2, 100 %). (LRMS ESI–) 253.1
(M – H, C15H13N2O2, 100 %). Mp 140–1478C.
Synthesised as for 10a from 8 and 4-cyanobenzaldehyde (9m) to
afford the title compound 10m as a white solid, 347 mg; 86 %
yield.
dH (400 MHz, DMSO) 8.47 (s, 1H), 7.90–7.84 (m, 2H), 7.66
(d, J 8.2, 2H), 7.61 (dd, J 7.7, 1.4, 1H), 7.31–7.22 (m, 2H), 6.76
(d, J 8.1, 1H), 6.71–6.65 (m, 1H), 5.85 (s, 1H). dC (101 MHz,
DMSO) 163.8, 147.81, 147.79, 134.0, 132.9, 128.1, 127.9,
119.1, 117.9, 115.4, 115.0, 111.5, 66.0. nmax (ATR)/cmꢀ1
3346 (NH), 2227 (CN), 1664 (C=O). m/z (LRMS ESIþ) 250.1

H
N. S. O’Brien and A. McCluskey
2-(3-Hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one
(10r)
2-(Benzofuran-2-ylmethyl)-2,3-dihydroquinazolin-4(1H)-
one (10v)
Synthesised as for 10a from 8 and 3-hydroxybenzaldehyde (9r)
to afford the title compound 10r as a white solid, 260 mg; 67 %
yield.
Synthesised as for 10a from 8 and benzofuran-2-carbaldehyde
(9v) to afford the title compound 10v as a white solid, 171 mg;
71 % yield.
dH (400 MHz, DMSO) 9.52 (d, J 1.7, 1H), 8.22 (s, 1H), 7.59
(dd, J 7.7, 1.4, 1H), 7.27–7.19 (m, 1H), 7.16 (t, J 8.1, 1H), 7.06
(s, 1H), 6.88 (t, J 4.0, 2H), 6.72 (ddd, J 7.1, 3.1, 1.8, 2H), 6.69–
6.62 (m, 1H), 5.64 (s, 1H). dC (101 MHz, DMSO) 163.7, 157.4,
147.9, 143.3, 133.4, 129.4, 127.4, 117.5, 117.1, 115.4, 114.9,
114.4, 113.7, 66.5. nmax (ATR)/cmꢀ1 3282 (NH), 3100 (OH),
1650 (C=O). m/z (LRMS ESIþ) 241.1 (M þ H, C14H13N2O2,
100 %), 481.2 (2M þ H, C14H13N2O2, 10 %); (ESI–) 239.1
(M– H, C14H11N2O2, 100 %), 479.2 (2M þ H, C14H11N2O2,
50 %). Mp 200–2098C.
dH (400 MHz, DMSO) 8.59 (d, J 2.9, 1H), 7.61 (ddd, J 8.3,
7.7, 1.1, 2H), 7.52 (dd, J 8.2, 0.6, 1H), 7.42 (s, 1H), 7.30–7.19
(m, 3H), 6.79 (d, J 7.7, 1H), 6.72–6.67 (m, 2H), 5.93 (t, J 2.9,
1H). dC (101 MHz, DMSO) 163.2, 157.3, 154.2, 146.9, 133.4,
127.5, 127.3, 124.6, 123.0, 121.4, 117.4, 115.0, 114.6, 111.2,
104.0, 60.4. nmax (ATR)/cmꢀ1 3269 (NH), 3178 (NH), 3010,
1662 (C=O). m/z (LRMS ESIþ) 265.1 (M þ H, C16H13N2O2,
100 %); (ESI–) 263.1 (M – H, C16H11N2O2, 100 %). Mp 192–
1988C.
2-Cyclopentyl-2,3-dihydroquinazolin-4(1H)-one (10w)
2-(3,4,5-Trihydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-
one (10s)
Synthesised as for 10a from 8 and cyclopentyl carboxaldehyde
(9w) to afford the title compound 10w as a white solid, 304 mg;
87 % yield.
Synthesised as for 10a from
8 and 3,4,5-trihydrox-
dH (400 MHz, DMSO) 7.91 (s, 1H), 7.56 (dd, J 7.7, 1.3, 1H),
7.23–7.19 (m, 1H), 6.76 (d, J 7.9, 1H), 6.64–6.60 (m, 1H), 6.53
(s, 1H), 4.48 (d, J 6.6, 1H), 2.25–2.10 (m, 1H), 1.65–1.43 (m,
8H). dC (101 MHz, DMSO) 163.6, 148.2, 133.0, 127.2, 116.6,
115.1, 114.3, 67.7, 44.9, 27.3, 27.2, 25.1, 25.0. nmax (ATR)/
cmꢀ1 3329 (NH), 3185 (NH), 2964 (CH2), 1635 (C=O). m/z
(LRMS ESIþ) 217.1 (M þ H, C13H17N2O, 100 %). Mp 166–
1778C.
ybenzaldehyde (9s) to afford the title compound 10s as a white
solid, 260 mg; 45 % yield.
dH (400 MHz, DMSO) 9.52 (d, J 1.7, 1H), 8.22 (s, 1H), 7.59
(dd, J 7.7, 1.4, 1H), 7.27–7.19 (m, 1H), 7.16 (t, J 8.1, 1H), 7.06
(s, 1H), 6.88 (t, J 4.0, 2H), 6.72 (ddd, J 7.1, 3.1, 1.8, 2H), 6.69–
6.62 (m, 1H), 5.64 (s, 1H). dC (101 MHz, DMSO) 163.7, 157.4,
147.9, 143.3, 133.4, 129.4, 127.4, 117.5, 117.1, 115.4, 114.9,
114.4, 113.7, 66.5. nmax (ATR)/cmꢀ1 3282 (NH), 3100 (OH)
1650 (C=O). m/z (LRMS ESIþ) 241.1 (M þ H, C14H13N2O2,
100 %), 481.2 (2M þ H, C14H13N2O2, 10 %); (ESI–) 239.1 (M-
H, C14H11N2O2, 100 %), 479.2 (2M þ H, C14H11N2O2, 50 %).
Mp 200–2098C.
2-Cyclohexyl-2,3-dihydroquinazolin-4(1H)-one (10x)
Synthesised as for 10a from 8 and cyclohexyl carboxaldehyde
(9x) to afford the title compound 10x as a white solid, 223 mg;
89 % yield.
dH (400 MHz, DMSO) 7.86 (s, 1H), 7.55 (dd, J 7.7, 1.5, 1H),
7.19 (ddd, J 8.7, 7.2, 1.6, 1H), 6.74 (d, J 7.7, 1H), 6.62–6.58
(m, 1H), 6.54 (s, 1H), 4.45–4.43 (m, 1H), 1.71–1.55 (m, 6H),
1.16–1.07 (m, 4H). dC (101 MHz, DMSO) 163.7, 148.3, 133.0,
127.2, 116.4, 114.8, 114.1, 68.6, 42.8, 27.0, 26.7, 25.9, 25.6,
25.5. nmax (ATR)/cmꢀ1 3336 (NH), 3172 (NH), 2921 (CH2),
1642 (C=O). m/z (LRMS ESIþ) 231.2 (M þ H, C15H19N2O,
100 %). Mp 176–1848C.
2-Phenethyl-2,3-dihydroquinazolin-4(1H)-one (10t)
Synthesised as for 10a from 8 and phenylacetaldehyde (9t) to
afford the title compound 10t as a yellow solid, 159 mg; 39 %
yield.
dH (400 MHz, DMSO) 8.02 (s, 1H, NH, H3), 7.60 (dd, J 7.7,
1.5, 1H), 7.32–7.15 (m, 6H), 6.77–6.73 (m, 1H), 6.71–6.65
(m, 2H), 4.74 (t, J 5.0, 1H, H2), 2.79–2.72 (m, 2H), 1.97–1.89
(m, 2H). dC (101 MHz, DMSO) 164.1, 148.6, 141.6, 133.1,
128.4 (2C), 128.3 (2C), 127.4, 125.8, 117.1, 115.1, 114.4,
64.0, 36.7, 29.3. nmax (ATR)/cmꢀ1 3302 (NH), 3175 (NH),
3000 (CH2), 1647 (C=O). m/z (LRMS ESIþ) 253.2 (M þ H,
C16H17N2O, 100 %); (ESI–), 251.1 (M – H, C16H15N2O,
100 %), 297.2 (M þ FA-H, C16H15N2O, 100 %). Mp
.1288C (dec.).
2-(Cyclohex-3-en-1-yl)-2,3-dihydroquinazolin-4(1H)-one
(10y)
Synthesised as for 10a from 8 and cyclohex-3-ene-1-carbalde-
hyde (9y) to afford the title compound 10y as an off-white solid,
337 mg; 92 % yield.
dH (400 MHz, DMSO) 7.95 (d, J 44.3, 1H), 7.56 (d, J 7.7,
1H), 7.23–7.19 (m, 1H), 6.75 (t, J 8.2, 1H), 6.65–6.53 (m, 2H),
5.65 (s, 2H), 4.56 (dd, J 4.2, 1.9, 1H), 2.05–1.97 (m, 4H), 1.83–
1.74 (m, 2H), 1.36–1.34 (m, 1H), dC (101 MHz, DMSO) 163.8,
163.7, 148.3, 148.3, 133.1, 133.0, 127.2, 126.8, 126.7, 126.0,
125.9, 116.6, 116.58, 114.9, 114.8, 114.2, 114.1, 67.9, 67.8,
38.9, 38.6, 25.9, 25.6, 24.70, 24.68, 23.1, 22.8. nmax (ATR)/
cmꢀ1 3353 (NH), 3172 (NH), 3036 (CH2), 160 (C=O). m/z
(LRMS ESIþ) 229.2 (M þ H, C14H17N2O, 100 %); (ESI–)
273.1 (M – HþFA, C15H19N2O2, 100 %). Mp 178–1858C.
2-(Benzo[c][1,2,5]thiadiazol-5-yl)-2,3-dihydroquinazolin-
4(1H)-one (10u)
Synthesised as for 10a from 8 and benzo[c][1,2,5]thiadiazole-5-
carbaldehyde (9u) to afford the title compound 10u as a brown
solid, 112 mg; 48 % yield.
dH (400 MHz, DMSO) 8.54 (s, 1H), 8.13 (d, J 9.2, 1H),
8.04 (s, 1H), 7.92 (dd, J 9.1, 1.6, 1H), 7.63 (dd, J 7.7, 1.3, 1H),
7.35 (s, 1H), 7.29–7.25 (m, 1H), 6.79 (d, J 8.0, 1H), 6.72–6.65
(m, 1H), 6.01 (s, 1H). dC (101 MHz, DMSO) 163.4, 154.2,
154.0, 147.4, 143.6, 133.6, 129.2, 127.4, 121.5, 118.5, 117.4,
114.9, 114.5, 65.8. nmax (ATR)/cmꢀ1 3243 (NH), 3029, 1654
(C=O). m/z (LRMS ESIþ) 283.1 (M þ H, C14H11N4OS,
100 %); (ESI–) 281.1 (M – H, C14H9N4OS, 100 %). Mp
216–2188C.
2-Butyl-2,3-dihydroquinazolin-4(1H)-one (10z)
Synthesised as for 10a from 8 and butyraldehyde (9z) to afford
the title compound 10z as a white solid, 136 mg; 34 % yield.
dH (400 MHz, DMSO) 7.87 (s, 1H), 7.58 (dd, J 7.7, 1.2, 1H),
7.24–7.20 (m, 1H), 6.73 (d, J 8.0, 1H), 6.65 (dd, J 11.0, 3.9, 1H),

Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones
I
6.55 (s, 1H), 4.68 (t, J 5.3, 1H), 1.64–1.61 (m, 2H), 1.40–1.28
(m, 4H), 0.88 (t, J 7.2, 3H). dC (101 MHz, DMSO) 163.9, 148.5,
133.0, 127.3, 116.9, 115.0, 114.4, 64.4, 34.7, 25.4, 22.1, 13.9.
nmax (ATR)/cmꢀ1 3340 (NH), 3178 (NH), 2926 (CH2), 1643
(C=O). m/z (LRMS ESIþ) 205.2 (M þ H, C12H17N2O, 100 %).
Mp 137–1438C.
113.4, 70.6. nmax (ATR)/cmꢀ1 3263 (NH), 3178 (NH), 3053
(CH), 1646 (C=O). m/z (LRMS ESIþ) 329.1 (M þ H,
79
13
81
13
C16H BrN2O, 100 %) 331.1 (M þ H, C16H BrN2O, 95 %).
Mp 180–1838C.
2-(Furan-2-yl)-2,3-dihydroquinazolin-4(1H)-one (10af)
No reaction observed.
2-Octyl-2,3-dihydroquinazolin-4(1H)-one (10aa)
2-(5-Methylfuran-2-yl)-2,3-dihydroquinazolin-4(1H)-one
(10ag)
Synthesised as for 10a from 8 and octylaldehyde (9aa) to afford
the title compound 10aa as a white solid, 113 mg; 34 % yield.
dH (400 MHz, DMSO) 7.87 (s, 1H), 7.58 (dd, J 7.7, 1.5, 1H),
7.22 (ddd, J 8.3, 7.2, 1.6, 1H), 6.73 (d, 1H), 6.65 (d, 1H), 6.55 (s,
1H), 4.68 (t, J 5.2, 1H), 1.68–1.55 (m, 2H), 1.44–1.39 (m, 2H),
1.31–1.25 (m, 8H), 0.87 (t, J 6.8, 3H). dC (101 MHz, DMSO)
163, 148.5, 133.0, 127.3, 116.8, 115.0, 114.3, 64.4, 35.0, 31.2,
28.9, 28.7, 23.2, 22.1, 13.9. nmax (ATR)/cmꢀ1 3333 (NH), 3185
(NH), 22925 (CH2), 1641 (C=O). m/z (LRMS ESIþ) 247.2
(M þ H, C15H23N2O, 100 %); (LRMS ESI–) 291.2 (M þ FA-H,
C16H25N2O3, 100 %). Mp 160–1638C.
No reaction observed
2-(5-Bromofuran-2-yl)-2,3-dihydroquinazolin-4(1H)-one
(10ah)
Synthesised as for 10a from 8 and 5-bromo-2-furfural (9ah) to
afford the title compound 10ah as an off-white solid, 123 mg;
25 % yield.
dH (400MHz, DMSO) 8.44 (s, 1H), 7.61 (s, 1H), 7.27 (s, 2H),
6.73 (d, J 30.9, 2H), 6.56–6.21 (m, 2H), 5.75 (s, 1H). dC
(101MHz, DMSO) 163.1, 156.6, 146.9, 133.4, 127.3, 121.0,
117.5, 114.9, 114.6, 112.3, 110.2, 60.0. nmax (ATR)/cmꢀ1 3270
(NH), 3165(NH), 1651 (C=O). m/z (LRMSESIþ) 293.1 (Mþ H,
2-(Naphthalen-1-yl)-2,3-dihydroquinazolin-4(1H)-one
(10ab)
Synthesised as for 10a from 8 and 2-naphthylaldehyde (9ab) to
afford the title compound 10ab as a white solid, 374 mg; 30 %
yield.
79
10
81
10
C12H BrN2O2, 100%), 295.1 (Mþ H, C12H BrN2O2, 100 %);
(LRMS ESI–) 291.1 (M – H, C12H789BrN2O2, 100 %), 293.1
(M – H, C12H881BrN2O2, 100 %). Mp .1508C (dec.).
dH (400 MHz, DMSO) 8.37 (s, 1H), 7.96–7.90 (m, 4H), 7.70
(dd, J 8.6, 1.6, 1H), 7.64 (dd, J 7.7, 1.5, 1H), 7.53 (dd, J 6.2, 3.3,
2H), 7.25 (ddd, J 8.3, 7.3, 1.6, 1H), 7.19 (s, 1H), 6.77 (d, J 7.7,
1H), 6.71–6.67 (m, 1H), 5.94 (s, 1H). dC (101 MHz, DMSO)
163.6, 147.9, 138.9, 133.4, 133.0, 132.5, 128.1, 128.0, 127.6,
127.4, 126.43, 126.38, 125.9, 124.8, 117.2, 114.9, 114.4, 66.8.
nmax (ATR)/cmꢀ1 3275 (NH), 8978 (CH), 1646 (C=O). m/z
(LRMS ESIþ) 275.1 (M þ H, C18H15N2O, 100 %); (LRMS
ESI–) 273.1 (M – H, C18H13N2O, 100 %). Mp 202–2068C.
2-(1H-Pyrrol-2-yl)-2,3-dihydroquinazolin-4(1H)-one (10ai)
No reaction observed.
2-(Thiophen-2-yl)-2,3-dihydroquinazolin-4(1H)-one (10aj)
Synthesised as for 10a from 8 and thiophen-2-carboxaldehyde
(9aj) to afford the title compound 10aj as a white solid, 309 mg;
80 % yield.
dH (400 MHz, DMSO) 8.44 (s, 1H), 7.62 (dd, J 7.7, 1.3, 1H),
7.45 (dd, J 5.0, 1.2, 1H), 7.26–7.24 (m, 2H), 7.12 (d, J 3.0, 1H),
6.98 (dd, J 5.0, 3.5, 1H), 6.76 (d, J 7.8, 1H), 6.70 (t, 1H), 6.02
(s, 1H). dC (101 MHz, DMSO) 163.1, 147.2, 146.4, 133.4, 127.3,
126.5, 125.9, 125.7, 117.5, 115.1, 114.7, 62.6. nmax (ATR)/cmꢀ1
3295 (NH), 3172 (NH), 1649 (C=O). m/z (LRMS ESIþ) 231.1
(M þ H, C12H11N2OS, 100 %); (LRMS ESI–) 229.1 (M-H,
C12H11N2OS, 100 %). Mp 197–2068C.
2-(Naphthalen-2-yl)-2,3-dihydroquinazolin-4(1H)-one
(10ac)
Synthesised as for 10a from 8 and 1-naphthylaldehyde (9ac) to
afford the title compound 10ac as a white solid, 130 mg; 86 %
yield.
dH (400 MHz, DMSO) 8.57–8.54 (m, 1H), 8.27 (s, 1H), 8.01–
7.96 (m, 2H), 7.72–7.69 (m, 2H), 7.59–7.51 (m, 3H), 7.28–7.24
(m, 1H), 7.08 (s, 1H), 6.76–6.71 (m, 2H), 6.49 (s, 1H). dC
(101 MHz, DMSO) 164.5, 148.9, 135.6, 134.2, 133.7, 131.0,
129.8, 129.1, 128.0, 126.51, 126.50, 126.3, 125.7, 125.1, 117.7,
115.4, 115.0, 66.4. nmax (ATR)/cmꢀ1 3359, 3217 (NH), 3004,
1649 (C=O). LRMS (ESIþ) 275.2 (M þ H, C18H15N2O, 100 %).
Mp 182–1868C.
(E)-2-(2-Nitrostyryl)-2,3-dihydroquinazolin-4(1H)-one
(10ak)
Synthesised as for 10a from 8 and (E)-3-(2-nitrophenyl)-
acrylaldehyde (9ak) to afford the title compound 10ak as a
yellow solid, 289 mg; 59 % yield.
dH (400 MHz, DMSO) 8.50 (d, J 8.9, 1H), 8.35 (s, 1H), 8.09
(d, J 7.0, 1H), 8.05 (dd, J 8.1, 1.1, 1H), 7.94 (dd, J 7.8, 1.5, 1H),
7.81–7.76 (m, 1H), 7.74 (d, J 15.8, 1H), 7.68–7.62 (m, 2H), 7.53
(td, J 7.7, 1.6, 1H), 7.37–7.31 (m, 2H), 7.23–7.21 (m, 1H). dC
(101 MHz, DMSO) 167.1, 163.2, 149.0, 148.2, 139.3, 133.6,
132.4, 131.9, 130.6, 129.9, 129.7, 128.7, 128.1, 126.3, 124.6,
118.9. nmax (ATR)/cmꢀ1 3249 (NH), 2971 (NH), 1668 (C=O),
1519 (NO), 1349 (NO). m/z (LRMS ESIþ) 296.1 (M þ H,
C16H14N3O3, 100 %). Mp 127–1348C.
(E)-2-(1,2-Diphenylvinyl)-2,3-dihydroquinazolin-4(1H)-
one (10ad)
No reaction observed.
(Z)-2-(1-Bromo-2-phenylvinyl)-2,3-dihydroquinazolin-
4(1H)-one (10ae)
Synthesised as for 10a from 8 and (Z)-2-bromo-3-phenylacry-
laldehyde (9ae) to afford the title compound 10ae as a pale
yellow solid, 212 mg; 40 % yield.
(E)-2-(2-(Furan-2-yl)vinyl)-2,3-dihydroquinazolin-4(1H)-
one (10al)
dH (400 MHz, DMSO) 8.30 (d, J 1.3, 1H), 7.64–7.63 (m, 2H),
7.58 (dd, J 7.7, 1.4, 1H), 7.43– 7.39 (m, 2H), 7.37 (dd, J 4.9, 3.6,
1H), 7.25–7.19 (m, 3H), 6.72 (d, J 8.0, 1H), 6.62 (t, 1H), 5.64 (s,
1H). dC (101 MHz, DMSO) 162.6, 146.9, 134.3, 133.4, 129.6,
129.0 (2C), 128.6, 128.5, 128.5, 128.4 (2C), 127.0, 116.6, 113.6,
Synthesised as for 10a from 8 and (E)-3-(furan-2-yl)-
acrylaldehyde (9al) to afford the title compound 10al as a white
solid, 109 mg; 28 % yield.

J
N. S. O’Brien and A. McCluskey
dH (400MHz, DMSO) 8.13 (s, 1H), 7.63–7.59 (m, 2H), 7.27–
(E)-2-Styrylquinazolin-4(3H)-one (11a)
7.22 (m, 1H), 6.87 (s, 1H), 6.74 (d, J 8.1, 1H), 6.71–6.65 (m, 1H),
6.54–6.48 (m, 3H), 6.12 (dd, J 15.8, 6.5, 1H), 5.26 (d, J 6.5, 1H).
dC (101MHz, DMSO) 163.3, 151.1, 147.6, 143.2, 133.3, 127.3,
126.7, 119.9, 117.2, 114.9, 114.6, 111.8, 109.6, 65.0. nmax (ATR)/
cmꢀ1 3236 (NH), 2971 (NH), 1634 (C=O). m/z (LRMS ESIþ)
241.1 (Mþ H, C14H13N2O2, 100 %). Mp 148–1518C.
Synthesised as for 10a from 8 and cinnamaldehyde (9aq) to
afford the title compound 11a as an off-white solid, 248 mg;
54 % yield.
dH (400MHz, DMSO) 12.33 (s, 1H), 8.11 (d, J 7.4, 1H), 7.95
(d, J 16.2, 1H), 7.81 (t, J 7.1, 1H), 7.72–7.63 (m, 3H), 7.50–7.40
(m, 4H), 7.01 (d, J 16.2, 1H). dC (101MHz, DMSO) 161.7, 151.4,
149.0, 138.3, 135.0, 134.5, 129.8, 129.1 (2C), 127.6 (2C), 127.1,
126.2, 125.9, 121.1, quaternary carbon not observed. nmax (ATR)/
cmꢀ1 3105 (NH), 3042 (CH), 1668 (C=O). m/z (LRMS ESIþ)
249.1 (M þ H, C16H13N2O, 100 %); (LRMS ESI–) 247.2 (M – H,
C16H11N2O, 100 %). Mp 243–2568C.
2-(5-Methyl-1H-indol-3-yl)-2,3-dihydroquinazolin-4(1H)-
one (10am)
Synthesised as for 10a from 8 and 5-methyl-1H-indole-3-car-
baldehyde (9am) to afford the title compound 10am as a pink
solid, 73 mg; 17 % yield.
(E)-2-(4-Methoxystyryl)quinazolin-4(3H)-one (11b)
dH (400 MHz, DMSO) 12.09 (s, 1H), 11.74 (s, 1H), 8.50 - 8.49
(m, 2H), 8.10 (dd, J 7.9, 1.0, 1H), 7.79– 7.75 (m, 2H), 7.41–7.35
(m, 2H), 7.06 (dd, J 8.3, 1.4, 1H), 2.47 (s, 3H). dC (101MHz,
DMSO) 162.1, 150.4, 149.8, 135.2, 134.3, 129.6, 129.1, 127.0,
125.81, 125.80, 125.1, 124.1, 122.1, 120.4, 111.6, 108.1, 21.5. m/
z (LRMS ESIþ) 276.2 (M þ H, C17H14N3O, 100 %); (ESI–)
274.1 (M – H, C17H12N3O, 100 %). nmax (ATR)/cmꢀ1 3385
(NH), 3114 (NH), 2965, 1663 (C=O). Mp .1558C (dec.).
Synthesised as for 10a from 8 and (E)-3-(4-methoxyphenyl)-
acrylaldehyde (9ar) to afford the title compound 11b as a yellow
solid, 165 mg; 37 % yield.
dH (400 MHz, DMSO) 12.25 (s, 1H), 8.10 (dd, J 7.9, 1.1, 1H),
7.91 (d, J 16.1, 1H), 7.81–7.77 (m, 1H), 7.66–7.60 (m 3H), 7.47–
7.43 (m, 1H), 7.02 (d, J 8.7, 2H), 6.85 (d, J 16.1, 1H), 3.81
(s, 3H). dC (101 MHz, DMSO) 161.8, 160.6, 151.7, 149.2, 138.0,
134.5, 129.3 (2C), 127.6, 127.0, 125.9, 125.8, 121.0, 118.5,
114.6 (2C), 55.3. nmax (ATR)/cmꢀ1 3100 (NH), 3049, 1668
(C=O). LRMS (ESIþ) 279.1 (M þ H, C17H15N2O2, 100 %);
(ESI–) 277.1 (M – H, C17H13N2O2, 100 %). Mp .2108C (dec.).
2-(5-Bromo-1H-indol-3-yl)-2,3-dihydroquinazolin-4(1H)-
one (10an)
No reaction observed.
(E)-2-(4-Bromostyryl)quinazolin-4(3H)-one (11c)
(E)-2-(4-(Dimethylamino)styryl)-2,3-dihydroquinazolin-
4(1H)-one (10ao)
Synthesised as for 10a from 8 and (E)-3-(4-bromophenyl)-
acrylaldehyde (9as) to afford the title compound 11c as a white
solid, 82 mg; 62 % yield.
No reaction observed.
dH (400 MHz, DMSO) 12.34 (s, 1H), 8.12 (dd, J 7.9, 1.0, 1H),
7.92 (d, J 16.2, 1H), 7.84–7.80 (m, 1H), 7.67 (dd, J 8.1, 6.1, 3H),
7.62 (d, J 8.6, 2H), 7.49 (t, J 7.5, 1H), 7.03 (d, J 16.2, 1H). dC
(101 MHz, DMSO) 162.2, 151.7, 149.4, 137.4, 135.0, 134.8,
132.5 (2C), 130.0 (2C), 127.6, 126.8, 126.3, 123.4, 122.4, 121.6.
2-(1H-Indol-3-yl)-2,3-dihydroquinazolin-4(1H)-one (10ap)
Synthesised as for 10a from 8 and 1H-indole-3-carbaldehyde
(9ap) to afford the title compound 10ap as an orange solid,
220 mg; 53 % yield.
dH (400 MHz, DMSO) 11.09 (s, 1H), 8.09 (s, 1H), 7.78–7.76
(m, 1H), 7.66 (dd, J 7.8, 1.4, 1H), 7.41–7.39 (m, 2H), 7.24 (dt,
1H), 7.11–7.10 (m, 1H), 7.01–6.98 (m, 1H), 6.92 (s, 1H), 6.76 (d,
J 8.0, 1H), 6.71–6.68 (m, 1H), 6.04 (s, 1H). dC (101 MHz,
DMSO) 164.2, 148.8, 136.6, 133.0, 127.5, 125.4, 124.7, 121.4,
120.0, 118.8, 117.0, 115.3, 114.40, 114.41, 111.7, 61.7. m/z
(LRMS ESIþ) 264.1 (M þ H, C16H14N3O, 100 %); (ESI–) 262
(M – H, C16H12N3O, 100 %). nmax (ATR)/cmꢀ1 3579, 3398,
3185 (NH), 2991, 1641 (C=O). Mp 196–2168C.
n
max (ATR)/cmꢀ1 3004, 1665 (C=O), 770 (C–Br). m/z (LRMS
ESIþ) 327 (M þ H, C16H12Br79N2O, 100 %) 329 (M þ H,
C16H12Br81N2O, 85 %); (ESI–) 325 (M – H, C16H10Br79N2O,
100 %), 327 (M – H, C16H10Br81N2O, 95 %). Mp 296–3108C.
(E)-2-(Hex-1-en-1-yl)quinazolin-4(3H)-one (11d)
Synthesised as for 10a from 8 and (E)-hex-2-enal (9at) to afford
the title compound 11d as a brown solid, 102 mg; 24 % yield.
dH (400MHz, DMSO) 8.14 (s, 1H), 7.94–7.88 (m, 2H), 7.64
(s, 1H), 2.85 (s, 1H), 2.64 (s, 1H), 1.79 (s, 1H), 1.36–1.28 (m, 4H),
0.89 (m, 4H). dC (101MHz, DMSO) 160.8, 135.9, 128.1, 126.8,
120.4, 32.9, 31.2, 29.6, 28.5, 27.5, 22.3, 22.1, 14.4. nmax (ATR)/
cmꢀ1 2908 (NH), 1708 (C=O). m/z (LRMS ESIþ) 229.1 (Mþ H,
C14H17N2O, 100 %); (LRMS ESI–) 227.1 (M – H, C14H15N2O,
100 %). Mp 147–1768C.
3-(4-Oxo-1,2,3,4-tetrahydroquinazolin-2-yl)-1H-indole-5-
carbonitrile (10aq)
Synthesised as for 10a from 8 and 3-formyl-1H-indole-5-car-
bonitrile (9aq) to afford the title compound 10aq as a yellow
solid, 103 mg; 35 % yield.
dH (400 MHz, DMSO) 12.35 (s, 1H), 12.30 (s, 1H), 9.10 (s,
1H), 8.71 (d, J 2.5, 1H), 8.12 (d, J 7.7, 1H), 7.80 (dt, J 14.9, 7.5,
2H), 7.67 (t, J 7.4, 1H), 7.61 (d, J 8.2, 1H), 7.44 (dd, J 15.9, 9.2,
1H). dC (101 MHz, DMSO) 162.0, 149.4, 149.3, 138.7, 134.5,
131.4, 127.6, 127.3, 125.8, 125.6, 125.5, 125.3, 120.6, 120.5,
113.6, 109.3, 103.2. nmax (ATR)/cmꢀ1 3282 (NH), 3120 (NH),
2227 (CN), 1679 (C=O). m/z (LRMS ESIþ) 287.1 (M þ H,
C17H11N4O, 100 %); (LRMS ESI–) 285.1 (M – H, C17H9N4O,
100 %). Mp .2508C (dec.).
Supplementary Material
Copies of the 1H and 13C NMR spectra of the compounds
reported in this work are available on the Journal’s website.
Conflict of Interest
The authors declare no conflicts of interest.
Acknowledgements
2-(1H-Indol-5-yl)-2,3-dihydroquinazolin-4(1H)-one (10ap)
N. S. O. is the recipient of a University of Newcastle Postgraduate Research
Scholarship (UNPRS) and this work was supported by the Australian
No reaction observed.

Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones
K
Research Council (ARC Discovery Project grant award number
DP180101781) and equipment grants from the Australian Cancer Research
Foundation and Ramaciotti Foundation. The authors would like to thank
Dr Enis Nadia Md Yusof (Universiti Putra Malaysia) for her invaluable
expertise with tin-based ICP analysis.
[15] K. Okumura, T. Oine, Y. Yamada, G. Hayashi, M. Nakama, J. Med.
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M. Chruszcz, W. Minor, M. L. Brown, J. Med. Chem. 2008, 51, 4620.
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