Easy access for the synthesis of 2-aryl 2,3-dihydroquinazolin-4(1H)-ones using gem-dibromomethylarenes as synthetic aldehyde equivalent

Article abstract of DOI:10.1039/c4ra02312a

One step synthesis of 2,3-dihydroquinazolin-4(1H)-ones from gem-dibromomethylarenes using 2-aminobenzamide is described. Gem-dibromomethylarenes are used as aldehyde equivalent for the efficient synthesis of 2,3-dihydroquinazolin-4(1H)-ones, this synthesis takes shorter reaction time with quick isolation and excellent product yield. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4ra02312a

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Easy access for the synthesis of 2-aryl 2,3-
dihydroquinazolin-4(1H)-ones using gem-
dibromomethylarenes as synthetic aldehyde
equivalent†
Cite this: RSC Adv., 2014, 4, 34479
Kereyagalahally H. Narasimhamurthy, Siddappa Chandrappa,
Kothanahally S. Sharath Kumar, Kachigere B. Harsha,
Hanumappa Ananda and Kanchugarakoppal S. Rangappa*
Received 17th March 2014
Accepted 17th July 2014
One step synthesis of 2,3-dihydroquinazolin-4(1H)-ones from gem-dibromomethylarenes using 2-
aminobenzamide is described. Gem-dibromomethylarenes are used as aldehyde equivalent for the
efficient synthesis of 2,3-dihydroquinazolin-4(1H)-ones, this synthesis takes shorter reaction time with
quick isolation and excellent product yield.
DOI: 10.1039/c4ra02312a
www.rsc.org/advances
We investigated model reaction between 2-aminobenzamide
and gem-dibromomethylarenes under different conditions, and
Introduction
Quinazolinone derivatives have drawn considerable attention the results are presented in Table 1.
1
a
1b
1c
due to their antidepressant, analgesic, diuretic, anti-
2a
2b
2c
histamine,
vasodilating,
antihypertensive,
and anti-
3
4
inammatory activities. They also possess anticancer activi- Results and discussion
ties like inhibition of tubulin formation, inhibition against
VEGFR2 tyrosine kinase and cell proliferation. These N-
containing heterocyclic compounds are integral part of many
drug molecules and several classical methods for the synthesis
of 2,3-dihydroquinazoline-4(1H)-ones are available.
Many transition metals like Sc, Ti, Co, Cu, Zn, Zr, and Ru are
used in the synthesis of 2,3-dihydroquinazoline-4(1H)-ones.
In addition, gem-dibromomethylarenes are used as aldehyde
equivalent in the synthesis of cinnamic acids,
benzothiazoles
mes. In continuation of our studies
using gem-dibromomethylarenes for the synthesis of 2,3-dihy-
droquinazoline-4(1H)-ones.
5,6
The synthesis of gem-dibromomethylarenes was initiated from
the corresponding commercially available methyl analogues
using N-bromo succinamide (2.0 equiv.) in carbon tetrachloride
with a catalytic amount of benzoyl peroxide (0.2 equiv.) under
reux conditions. A mixture of 1-chloro-3-(dibromomethyl)
benzene 1a (1.0 equiv), 2-aminobenzamide 2a (1.1 equiv.),
potassium tert-butoxide (t-BuOK) (0.5 equiv.) in anhydrous
pyridine and dimethylformamide (3 : 1 ratio) solvent was stir-
red at room temperature, but only trace amount of product was
obtained even aer 6 h of stirring (entry 1, Table 1). Improve-
ment in product yield (entry 2, Table 1) was achieved when the
7
8–15
16a–g
17a
cinnamic
and aryl oxi-
(Scheme 1), we tried
1
7b
18a
18b
esters,
benzimidazoles,
1
8c
18a,b,c
ꢀ
reaction mixture was heated at 80 C for 6 h. The reaction was
monitored by increasing the equivalence of t-BuOK, and the
maximum yield was obtained with 1.0 mmol of t-BuOK, and the
starting material was consumed in 4 h as indicated by TLC.
Aer workup and purication by column chromatography, 2-(3-
chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one 3a was isolated
with 90% yield (entries 3 and 4, Table 1), and any increase in the
equivalent of base did not inuence the yield. Bases, like
N-ethyldiisopropylamine, triethylamine, DABCO and DBU, did
not promote the reaction (entries 5–8, Table 1), whereas pyrro-
lidine, morpholine and piperidine gave less yields in 6 h (entries
Scheme
equivalent in synthesis.
1 Examples of gem-dibromomethylarenes as aldehyde
9
–11, Table 1). Both aromatic and heteroaromatic gem-dibro-
Department of Studies in Chemistry, University of Mysore, Manasagangotri,
Mysore-570006, India. E-mail: rangappaks@gmail.com; rangappaks@chemistry.
uni-mysore.ac.in; Fax: +91-821-2412191; Tel: +91-821-2419661
momethylarenes bearing various functionalities, such as
chloro, bromo, uoro, methoxy, ester, tert-butyl and triuoro
methyl, –OTHP, –OTBDMS groups, survived the reaction
and provided high yields of corresponding products (Table 2).
†
Electronic supplementary information (ESI) available. See DOI:
0.1039/c4ra02312a
1
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a
Table 1 Optimization experiments for the synthesis of 3a
ꢀ
b
Entry
Base
Equivalent
Temp. ( C)
Time (h)
Yield (%) of 3a
1
2
3
4
5
6
7
8
9
t-BuOK
t-BuOK
t-BuOK
t-BuOK
DIPEA
TEA
DABCO
DBU
0.5
0.5
1.0
1.5
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0–25
80
80
80
80
80
80
80
80
80
80
6
6
4
4
6
6
6
6
6
6
6
Trace
45
90
89
—
—
—
—
Pyrrolidine
Morpholine
Piperidine
18
22
30
1
1
0
1
a
b
Reaction condition: gem-dibromomethylarenes 1 (1.0 equiv.) and 2-aminobenzamide 2 (1.1 equiv.), (t-BuOK) 1.0 mmol. Isolated yields aer
column chromatography.
The reaction of gem-dibromomethylarenes with 2-amino- butoxide (0.366 g, 0.00327 mol) was added to a suspension of 4-
benzamide yielded corresponding 2,3-dihydroquinazolin-4(1H)- tertiary butylbenzalbromide (1f) (1 g, 0.00327 mol) and 2-amino-
ones, and the proposed reaction mechanism is shown in 5-chlorobenzamide (2b) (0.614 g, 0.0036 mol) in pyridine–
Scheme 2.
dimethyl formamide (6.0 : 2.0 mL) solvent mixture. The resul-
tant mixture was heated at 80 C for 4 h. Progress of the reaction
ꢀ
was monitored by TLC. The reaction mass was mixed with water
then extracted with ethyl acetate (2 ꢁ 20 mL), and the organic
Conclusion
In summary, this is an effective and efficient method of phase was washed with brine solution and dried over anhydrous
conversion of substituted 2-aminobenzamide into correspond- sodium sulphate. The organic phase was evaporated and the
ing 2,3-dihydroquinazolin-4(1H)-ones using gem-dibromome- crude product was puried by column chromatography using
thylarenes under mild reaction conditions. The use of gem- silica gel mesh 100–200 (30% EtOAc in hexane).
dibromomethylarenes for the direct synthesis of biologically
important 2,3-dihydroquinazolin-4(1H)-ones has been indi- White solid; m.p. 188.9–189.9 C. (Lit. 189.8–189.9 C) IR (KBr)
2-(3-Chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one
(3a).
ꢀ
11
ꢀ
ꢂ1
1
cated. As this reaction provides 2,3-dihydroquinazolin-4(1H)-
n
max 3290, 3199, 1652, 1613 cm . H NMR (400 MHz, DMSO-
ones in a single step from gem-dibromomethylarenes, it is one
d
6
): d 8.42 (s, 1H), 7.63–7.60 (m, 1H), 7.53 (s, 1H), 7.47–7.31 (m,
of the easiest pathways for accessing these compounds and the 3H), 7.23–7.27 (m, 2H), 6.77 (d, J ¼ 7.6 Hz, 1H), 6.69 (t, J ¼ 7.6
1
3
starting material is easily available. This transformation would Hz, 1H), 5.77 (s, 1H) ppm; C NMR (100 MHz, DMSO-d
have many applications in synthetic chemistry.
6
): d
163.9, 147.9, 144.8, 133.9, 133.4, 130.7, 128.7, 127.8, 127.2,
25.8, 117.8, 115.3, 114.9, 66.0 ppm; MS(ESI): m/z ¼ 258.8,
1
+
HRMS (ESI): calcd for [C14
59.7105.
2,4-Dichloro, 3-dihydroquinazolin-4(1H)-one (3b). White
2
H13ClN O + H ]: 259.7109, found
Experimental section
2
General information
ꢀ
15
ꢀ
solid, m.p. 182–184 C (Lit. 181–185 C); IR (KBr): 3337, 3179,
025, 1661 cm . H NMR (DMSO-d
Melting points were recorded (uncorrected) on a Buchi Melting
Point B-545 instrument. Infrared (IR) spectra were recorded
using a Jasco FTIR-4100 series. All reagents and solvents used
were commercially procured and used as received. The H NMR
spectra were measured on a Bruker DPX-400 at 400 MHz with
TMS as internal standard. The C NMR spectra were measured
on a Bruker DPX-400 at 100 MHz. The mass spectra were
recorded on a JEOL JMS-AX505HA mass spectrometer.
ꢂ1
1
3
7
6
, 400 MHz): 8.25 (s, 1H),
.68–7.65 (m, 3H), 7.50–7.47 (m, 1H), 7.29–7.24 (t, J ¼ 7.5 Hz,
1
1H), 7.04 (s, 1H), 6.93 (d, J ¼ 6.4 Hz, 1H), 6.71 (t, J ¼ 8.1 Hz, 1H),
13
6
.1 (s, 1H) ppm; C NMR (100 MHz DMSO-d
136.9, 133.9, 133.5, 132.9, 130.9, 128.9, 128.6, 127.4, 117.6,
14.7, 114.6, 63.3 ppm; MS(ESI): m/z ¼ 293.148, HRMS (ESI):
6
): d 163.6, 147.5,
1
3
1
+
calcd for [C H Cl N O + H ]: 294.1559, found 294.1556.
14 11
2 2
2
-(Pyridin-4-yl)-2,3-dihydroquinazolin-4(1H)-one (3c). Light
yellow solid; m.p.: 187–188 C (lit. not reported) IR (KBr): 2922,
Typical procedure for the synthesis of 2-(4-tert-butylphenyl)-
ꢀ
8
6-chloro-2,3-dihydroquinazolin-4(1H)-one (3f). Potassium tert-
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Table 2 2-Aryl-2,3-dihydro quinazolin-4(1H)-ones results
a
b,c
Entry (Ar) substrate (1)
Yield (1) (%) (2)
Product (3)
Time (h) Yield (3) (%)
1
11
1
87
R ¼ –H, R ¼ –H, 2a
4
90
1
15
2
84
R ¼ –H, R ¼ –H, 2a
4
88
1
8
3
78
R ¼ –H, R ¼ –H, 2a
4.5
84
1
9
4
80
R ¼ –H, R ¼ –H, 2a
4
86
1
5
81
R ¼ –H, R ¼ –H, 2a
4
78
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Table 2 (Contd.)
a
b,c
Entry (Ar) substrate (1)
Yield (1) (%) (2)
Product (3)
Time (h) Yield (3) (%)
1
6
86
R ¼ Cl, R ¼ –H, 2b
4
85
1
7
84
R ¼ Cl, R ¼ –H, 2b
4
86
1
8
87
R ¼ OMe, R ¼ OMe, 2c
4
90
1
9
1g
—
R ¼ OMe, R ¼ OMe, 2c
4
81
1
1
0
77
R ¼ –H, R ¼ Cl, 2d
4
78
1
1
1
1e
—
R ¼ –H, R ¼ Cl 2d
4
83
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Table 2 (Contd.)
a
b,c
Entry (Ar) substrate (1)
Yield (1) (%) (2)
Product (3)
Time (h) Yield (3) (%)
1
12
13
14
80
—
85
R ¼ –H, R ¼ Cl, 2d
4
4
4
79
85
88
1
1f
R ¼ –H, R ¼ Cl, 2d
1
R ¼ –H, R ¼ Br, 2e
1
1
5
1i
—
R ¼ –H, R ¼ Br, 2e
4
89
1
1
6
45
R ¼ –H, R ¼ –H, 2a
4
60
1
1
7
84
R ¼ –H, R ¼ –H, 2a
4
75
a
b
c
Substrates are prepared from the commercial methyl analogues by radical bromination. Isolated yields of product (3). Literature reported
compounds.
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Scheme 2 Proposed mechanism of reaction between gem-dibromomethylarene and 2-aminobenzamide in pyridine/dimethyl formamide.
ꢂ1
1
2
(
853, 1674, 1605, cm . H NMR (400 MHz, DMSO-d
6
): d ¼ 8.88
6-Chloro-2-(3,4,5-trimethoxyphenyl)-2,3-dihydroquinazolin-
ꢀ
d, 2H, J ¼ 6.0 Hz), 8.36 (d, 2H, J ¼ 7.5 Hz), 8.17 (d, 2H, J ¼ 4.5 4(1H)-one (3g). White solid; m.p.: 158–160 C. IR (KBr) n
max
ꢂ1
1
Hz), 7.88 (d, 2H, J ¼ 3.0 Hz), 7.63–7.58 (m, 1H), 5.85 (s, 1H), 5.04 3274.90, 3197.76, 2964.39, 2929.67, 1654, 1612.33 cm
.
H
1
3
(
1
s, 1H) ppm; C NMR (100 MHz, DMSO-d
6
): d ¼ 160.93, 147.98, NMR (400 MHz, DMSO-d ): d 8.36 (s, 1H), 7.54–7.53 (d, J ¼ 2.4
6
46.88, 132.95, 126.34, 125.84, 124.46, 120.22, 69.15 ppm; Hz, 1H), 7.29–7.24 (m, 2H), 6.82–6.77 (m, 4H), 5.72 (S, 1H), 3.76
+
13
MS(ESI): m/z ¼ 225.245. HRMS (ESI): calcd for [C H N O + H ]: (s, 6H), 3.64 (s, 3H) ppm; C NMR (100 MHz, DMSO-d ): d
1
3
12
3
6
2
26.2539. Found 226.2535.
162.49, 152.76, 146.73, 137.69, 136.17, 133.02, 126.40, 120.86,
Methyl 4-(4-oxo-1,2,3,4-tetrahydroquinazolin-2-yl)benzoate 116.42, 116.12, 104.45, 66.73, 59.95, 59.71, 55.92 ppm; MS(ESI):
9
ꢀ
+
(
(
3d). White solid; m.p.: 200.2–202.4; (lit. 199.2–202.3 C). IR m/z ¼ 348.088, HRMS (ESI) calcd for [C H ClN O + H ]
1
7
18
2 4
ꢂ1 1
KBr): 3328, 3025, 2930, 1760, 1610 cm . H NMR (400 MHz, 349.7888, found 349.7885.
DMSO-d
6
): d 8.40 (s, 1H), 7.97 (d, J ¼ 8.3 Hz, 2H), 7.64–7.57 (m,
6,7-Dimethoxy-2-(4-(triuoromethyl)phenyl)-2,3-dihydro-
ꢀ
3
1
H), 7.28–7.22 (m, 2H), 6.75 (d, J ¼ 7.5 Hz 1H), 6.68 (td, J ¼ 7.5, quinazolin-4(1H)-one (3h). Light yellow solid; m.p.: 188–189 C;
1
3
.0 Hz, 1H), 5.84 (t, J ¼ 2.1 Hz, 1H), 3.85 (s, 3H) ppm; C NMR IR (KBr) n
3301.91, 3197.76, 2925.81, 2852.52, 1649.02,
max
ꢂ1
1
(100 MHz, DMSO-d ): d 165.91, 163.36, 147.50, 146.94, 133.40, 1618.17 cm ; H NMR (400 MHz, DMSO-d ): d 8.18 (s, 1H),
6
6
1
1
29.56, 129.22, 129.22, 127.33, 127.14, 127.14, 117.26, 114.86, 7.75–7.67 (m, 4H), 7.08 (s, 1H), 6.91 (s, 1H), 6.35 (s, 1H), 5.77 (s,
1
3
14.43, 65.88, 52.16 ppm; MS(ESI): m/z ¼ 282.294, HRMS (ESI) 1H), 3.72 (s, 3H), 3.65 (S, 3H) ppm; C NMR (100 MHz, DMSO-
+
calcd for [C16
H
15
N
2
O
3
+ H ]: 283.3019, found 283.3015.
d6): d 163.44, 153.93, 146.60, 143.07, 141.58, 127.74, 127.54,
2
-(5-Phenylpyridin-2-yl)-2,3-dihydroquinazolin-4(1H)-one (3e). 125.18, 125.15, 125.04, 109.74, 106.62, 97.99, 65.92, 55.74, 55.34
ꢀ
Light yellow solid; m.p.: 185–186 C; IR (KBr) nmax 3184.26, ppm; MS(ESI): m/z
066.61, 2929.67, 1666.38, 1610.45 cm . H NMR (400 MHz, [C H F N O + H ] 353.3157, found 353.3155.
¼
352.307, HRMS (ESI) calcd for
ꢂ1
1
+
3
17 16 3 2 3
DMSO-d
6
): d 8.66–8.64 (d, J ¼ 4.8 Hz, 1H), 8.32 (s 1H), 8.09–8.07
6,7-Dimethoxy-2-(3,4,5-trimethoxyphenyl)-2,3-dihydro-
ꢀ
(
d, J ¼ 8.4 Hz, 2H), 7.95–7.93 (d, J ¼ 8 Hz, 1H), 7.88–7.84 (tt, quinazolin-4(1H)-one (3i). Light red solid; m.p.: 242–244 C. IR
J ¼ 1.6 Hz, 1H), 7.62–7.58 (m 3H), 7.35–7.32 (m, 1H), 7.26–7.22 (KBr) n
3353.98, 3197.76, 2937.38, 2837.09, 1654.81, 1620.09,
max
1
ꢂ1
(
6
tt, J ¼ 8.4 Hz, 1H), 7.15 (s, 1H), 6.76–6.74 (d, J ¼ 8 Hz, 1H), 6.69– cm . H NMR (400 MHz, DMSO-d ): d 7.49 (s, 1H), 7.13 (s, 1H),
6
1
3
.52 (tt, J ¼ 8 Hz, 1H), 5.8 (s, 1H) ppm; C NMR (100 MHz, 6.85 (s, 2H), 6.7 (s, 1H), 6.4 (s, 1H), 5.64 (s, 1H), 3.78 (s, 3H) ppm;
13
DMSO-d
6
): d 163.52, 155.57, 149.54, 147.76, 142.41, 138.8, 137.2,
C NMR (100 MHz, DMSO-d ): d 163.82, 153.78, 152.83, 152.64,
6
133.3, 127.34, 127.22, 126.45, 122.68, 120.29, 117.13, 114.97, 143.75, 141.55, 137.48, 136.52, 109.79, 108.24, 104.96, 104.80,
1
14.42, 66.18 ppm; MS(ESI): m/z ¼ 301.122, HRMS (ESI) calcd 97.99, 67.30, 59.91, 55.87, 55.77, 55.69, 55.35 ppm; MS(ESI): m/z
+
+
for [C19
H
15
N
3
O + H ] 302.3498, found 302.3495.
¼ 374.387, HRMS (ESI) calcd for [C H N O + H ] 375.3957,
1
9
23 2 6
2
-(4-tert-Butylphenyl)-6-chloro-2,3-dihydroquinazolin-4(1H)- found 375.3954.
ꢀ
one (3f). Light yellow solid; m.p.: 180–182 C; IR (KBr) n
3
2-(2-Bromo-5-chlorophenyl)-7-chloro-2,3-dihydroquinazolin-
max
ꢂ1 1
ꢀ
328.91, 3257.55, 2929.67, 1741.60, 1612.38 cm . H NMR (400 4(1H)-one (3j). White solid; m.p.: 197–198 C; IR (KBr) nmax
MHz, DMSO-d
6
): d 8.38 (s, 1H), 7.53–7.52 (d, J ¼ 2.4 Hz, 1H), 7.42– 3353.98, 3288.4, 3182.33, 3051.18, 2921.96, 2854.45, 1694.02,
ꢂ1
1
7
.38 (m, 4H), 7.27–7.24 (m, 2H), 6.75–6.73 (d, J ¼ 8.4 Hz, 1H), 5.73 1610.45 cm ; H NMR (400 MHz, DMSO-d ): d 8.33 (s, 1H), 7.74–
6
1
3
(s, 1H), 1.26 (S, 9H) ppm; C NMR (100 MHz, DMSO-d
6
): 7.7 (m, 1H), 7.63 (s, 1H), 7.41–7.38 (dd, J ¼ 2.6 Hz, 1H), 7.29–7.22
d 162.40, 151.13, 146.62, 138.18, 132.96, 126.59, 126.35, 126.20, (m, 2H), 6.81–6.8 (d, J ¼ 1.2 Hz, 1H), 6.75–6.72 (dd, J ¼ 1.8 Hz, 1H),
13
125.11, 120.61, 116.31, 116, 66.27, 34.28, 31.04 ppm; MS(ESI): 6.1 (s, 1H) ppm; C NMR (100 MHz, DMSO-d ): d 162.57, 160.13,
6
+
m/z ¼ 314.119. HRMS (ESI) calcd for [C H ClN O + H ] 148.35, 141.02, 138.01, 134.65, 129.35, 117.92, 117.6, 116.58,
1
8
20
2
315.8172 found 315.8170.
115.99, 115.75, 113.27, 66.24 ppm; MS(ESI): m/z ¼ 355.589,
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+
HRMS(ESI) calcd for [C14
H
10BrClFN
2
O + H ] 356.5974, found 126.82, 125.16, 119.96, 116.40, 115.28, 115.07, 113.88, 65.75
3
56.5971.
ppm; MS (ESI): m/z ¼ 400.04, HRMS (ESI) calcd for [C H -
1
4
10
+
7-Chloro-2-(5-phenylpyridin-2-yl)-2,3-dihydroquinazolin-4(1H)- Br FN O + H ] 401.0484, found 401.0481.
2 2
ꢀ
one (3k). Brown solid; m.p.: 208–210 C; IR (KBr) n
3
NMR (400 MHz, DMSO-d
3193.9,
2-(4-(Tetrahydro-2H-pyran-2-yloxy)phenyl)-2,3-dihydroquinazolin-
max
ꢂ1
1
ꢀ
068.53, 2923.88, 2854.45, 2813.95, 1666.38, 1610.45 cm ; H 4(1H)-one (3p). White solid; m.p.: 136–138 C; IR (KBr) nmax
ꢂ1
1
6
): d 8.66–8.65 (d, J ¼ 4.4 Hz, 1H), 8.45 3327, 3028, 2932, 1738, 1615 cm ; H NMR (400 MHz, DMSO-
(
1
s, 1H), 8.11–8.09 (d, J ¼ 8.4 Hz, 1H), 7.95–7.93 (d, J ¼ 8 Hz,
d
6
): d 8.16 (s, 1H), 7.59–7.57 (d, J ¼ 8 Hz, 1H), 7.39–7.37 (d, J ¼ 8
H), 7.89–7.84 (tt, J ¼ 1.46 Hz, 1H), 7.62–7.56 (m, 4H), 7.43 (s, Hz, 2H), 7.23–7.19 (t, J ¼ 7.6 Hz, 1H), 7.02–6.98 (m, 3H), 6.72–
H), 7.36–7.33 (m, 1H), 6.8–6.79 (d, J ¼ 2 Hz, 1H), 6.69–6.67 6.63 (m, 2H) 5.67 (s, 1H), 5.45 (s, 1H), 3.72–3.67 (m, 1H), 3.52–
1
1
3
13
(
dd, J ¼ 2 Hz, 1H), 5.86 (s, 1H) ppm; C NMR (100 MHz, 3.48 (m, 1H), 1.88–1.69 (m, 3H), 1.60–1.48 (m, 4H) ppm;
C
DMSO-d ): d 162.63, 155.48, 149.53, 148.66, 142.04, 138.94, NMR (100 MHz, DMSO-d ): 164.13, 157.07, 148.43, 134.88,
6
6
1
1
3
37.81, 137.37, 137.21, 129.32, 128.35, 127.1, 126.54, 122.69, 134.86, 133.69, 128.54, 127.78, 117.52, 116.63, 115.39, 114.83,
20.29, 117.04, 113.62, 113.42, 66.07 ppm; MS(ESI): m/z ¼ 96.04, 66.79, 61.91, 30.21, 25.11, 18.98 ppm; MS (ESI): 324.14,
+
+
35.787, HRMS (ESI) calcd for [C19
H15ClN
3
O + H ] 336.7949, HRMS (ESI) calcd for [C19
H
20
N
2
O
3
+H ] 325.1552, found
found 336.7945.
325.1550.
7
-Chloro-2-(2,5-dimethoxyphenyl)-2,3-dihydroquinazolin-4(1H)-
2-(4-(tert-Butyldimethylsilyloxy)phenyl)-2,3-dihydroquinazolin-
ꢀ
ꢀ
one (3l). Light yellow solid; m.p.: 208–210 C; IR (KBr) nmax 4(1H)-one (3q). White solid; m.p.: 139–141 C; IR (KBr) nmax
330.84, 3298.05, 3234.4, 3060.82, 2962.46, 2867.95, 1643.24, 3329.86, 3032.60, 2928.72, 1740.30, 1612.30 cm ; H NMR (400
ꢂ1
1
3
1
7
6
ꢂ1
1
610.45 cm ; H NMR (400 MHz, DMSO-d ): d 8.11 (s, 1H), MHz, DMSO-d ): d 8.17 (s, 1H), 7.64–7.62 (dd, J ¼ 1.6 Hz, 1H),
6
6
.61–7.59 (d, J ¼ 8.4 Hz, 1H), 7.04 (s, 1H), 6.99–6.96 (m, 1H), 7.41–7.39 (dd, J ¼ 2 Hz, 2H), 7.28–7.24 (m, IH), 7.02 (s, 1H),
.9–6.87 (m, 2H), 6.817–6.813 (d, J ¼ 1.6 Hz, 1H), 6.67–6.65 (dd, 6.89–6.87 (dd, J ¼ 2 Hz, 2H), 6.77–6.75 (d, J ¼ 8.4 Hz, 1H) 6.71–
1
3
J ¼ 2 Hz, 1H), 5.99 (s, 1H), 3.77 (s, 3H), 3.66 (s, 3H) ppm;
C
6.67 (m, 1H), 5.72 (s, 1H), 1.02–0.92 (m, 9H), 0.25–0.15 (m, 6H)
1
3
6 6
NMR (100 MHz, DMSO-d ): d 162.91, 152.85, 150.36, 148.71, ppm; C NMR (100 MHz, DMSO-d ): 164.07, 155.77, 148.45,
1
1
37.74, 129.58, 129.21, 124.74, 116.92, 113.61, 113.5, 113.34, 134.8, 133.69, 128.78, 127.77, 119.97, 117.50, 115.32, 114.81,
12.24, 61.07, 55.99, 55.36 ppm; MS(ESI): m/z ¼ 318.754. 66.85, 26.0, 18.38, ꢂ4.08 ppm; MS (ESI): 354.17, HRMS (ESI)
+
+
HRMS (ESI) calcd for [C H ClN O +H ] 319.7628, found calcd for [C H N O Si + H ] 355.1852, found 358.1948.
1
6
16
2
3
20 26 2 2
319.7628.
2
-(4-tert-Butylphenyl)-7-chloro-2,3-dihydroquinazolin-4(1H)-
ꢀ
Acknowledgements
one (3m). Light yellow solid; m.p.: 110–112 C; IR (KBr) nmax
3
332.76, 3170.76, 3031.89, 2925.81, 2831.31, 1656.74, 1608.52
KHN is grateful to UGC, RFSMS Govt. of India for nancial
support, KSR is grateful to DST, CSIR, for the nancial assis-
tance under different projects: no. DST/INT/SA/P-05/2011-12,
dated 10-01-12; INT/Indo-Korea/122/2011-12, dated 13.09.2011.
no. 01 (2434)/10/EMR-II, dated 28.12.2010; IFCPAR Sanction no.
IFC/4303-1/2010-11 dated 22/12/2010.
ꢂ1
1
cm ; H NMR (400 MHz, DMSO-d
6
): d 8.31 (s, 1H), 8.14–8.1 (dd,
J ¼ 2.6 Hz, 1H), 7.6–7.38 (m, 4H), 7.3 (s, 1H), 6.757–6.752 (d, J ¼
1
3
2
Hz, 1H), 6.67–6.65 (dd, J ¼ 2 Hz, 1H), 5.75 (s, 1H) ppm;
C
NMR (100 MHz, DMSO-d ): d 162.71, 151.17, 148.8, 138.24,
6
1
1
37.72, 129.13, 127.68, 126.55, 125.43, 125.3, 116.9, 113.6,
13.31, 66.33, 34.29, 31.04, 30.84 ppm; MS(ESI): m/z ¼ 314.809,
+
HRMS (ESI) calcd for [C18
H
20ClN
2
O + H ] 315.8172, found
3
15.8170.
References
7-Bromo-2-(3,4-dimethoxyphenyl)-2,3-dihydroquinazolin-4(1H)-
ꢀ
one (3n). White solid; m.p.: 137–138 C; IR (KBr) nmax 3298.26,
1 (a) Rexall Drug Co., U.S. Patent 3257397, 1966; (b)
K. Okumura, T. Oine, Y. Yamada, G. Hayashi and
M. Nakama, J. Med. Chem., 1968, 11, 348; (c) E. Cohen,
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3
1
7
182.33, 3070.46, 2956.67, 2923.67, 2923.88, 2852.52, 1700,
ꢂ1
1
610 cm ; H NMR (400 MHz, DMSO-d ): d 8.38 (s, 1H), 7.52–
6
.49 (m, 3H), 7.33 (s, 1H), 7.24–7.2 (m, 1H), 6.94–6.93 (d, J ¼ 2
Hz, 1H), 6.83–6.80 (dd, J ¼ 1.8 Hz, 1H), 5.81 (s, 1H), 3.68 (s, 6H)
1
3
ppm; C NMR (100 MHz, DMSO-d
6
): d 162.65, 148.42, 141.06,
34.75, 129.42, 127, 120.44, 118.16, 117.94, 116.63, 115.98,
15.74, 113.57, 66.20, 55.42, 55.36 ppm; MS(ESI): m/z ¼ 363.205,
1
1
+
2 3
HRMS (ESI) calcd for [C16H16BrN O +H ] 364.2138, found
364.2135.
7
-Bromo-2-(2-bromo-5-uorophenyl)-2,3-dihydroquinazolin-
3 D. A. Erlanson, R. S. McDowell and T. O. Brien, J. Med. Chem.,
2004, 47, 3463.
ꢀ
4
3
1
7
(1H)-one (3o). White solid; m.p.: 206–207 C; IR (KBr) nmax
294.36, 3194.33, 3074.5, 2958.67, 2926.86, 2854.53, 1705.1,
4 Y. Xia, Z. Y. Yang, M. J. Hour, S. C. Kuo, P. Xia, K. F. Bastow,
Y. Nakanishi, P. Nampoothiri, T. Hackl, E. Hamel and
K. H. Lee, Bioorg. Med. Chem. Lett., 2001, 11, 1193.
5 M.-J. Hour, E. Hamel, L.-J. Huang, K.-H. Lee, S.-C. Kuo,
Y. Xia, K. Bastow and Y. Nakanishi, J. Med. Chem., 2000,
43, 4479.
ꢂ1
1
605 cm ; H NMR (400 MHz, DMSO-d
6
): d 8.34 (s, 1H), 7.74–
.7 (m, 1H), 7.57–7.55 (d, J ¼ 8.4 Hz, 1H), 7.40–7.37 (dd, J ¼ 3.2
Hz, 1H),7.28–7.23 (m, 2H), 6.963–6.960 (d, J ¼ 1.2 Hz, 1H), 6.89–
1
3
6
.86 (dd, J ¼ 1.8 Hz, 1H), 6.09 (s, 1H) ppm; C NMR (100 MHz,
DMSO-d ): d 162.69, 160.91, 148.74, 137.49, 129.39, 128.95,
6
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34486 | RSC Adv., 2014, 4, 34479–34486
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