Cyclisation of 2-(2-aminophenyl)quinazolin-4(3H)-one reexamined: Formation of isomeric angular fused quinazolinoquinazolinones and their spectroscopic identification

Article abstract of DOI:10.1016/j.tetlet.2012.03.055

Cyclisation of 2-(2-aminophenyl)quinazolin-4(3H)-ones on to N₃ and on to N₁ leading to 6-alkyl-(8H)-quinazolino[4,3-b]quinazolin-8- one and 6-alkyl-(13H)-quinazolino[3,4-a]quinazolin-13-one, respectively was described for the first time. The differences in the IR and carbon NMR data of these isomeric fused quinazolinoquinazolinones afford a useful method for distinguishing between the two series.

Full text of DOI:10.1016/j.tetlet.2012.03.055

Tetrahedron Letters 53 (2012) 2643–2646
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Tetrahedron Letters
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Cyclisation of 2-(2-aminophenyl)quinazolin-4(3H)-one reexamined: formation
of isomeric angular fused quinazolinoquinazolinones and their
spectroscopic identification q
Somepalli Venkateswarlu a, , Meka Satyanarayana a, Gandrothu Narasimha Murthy a, Vidavalur Siddaiah b
⇑
a Drug Discovery, Laila Impex Research Centre, No. 1, Phase III, Jawahar Autonagar, Vijayawada 520 007, India
b Department of Organic Chemistry, School of Chemistry, Andhra University, Visakhapatnam 530 003, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Cyclisation of 2-(2-aminophenyl)quinazolin-4(3H)-ones on to N3 and on to N1 leading to 6-alkyl-(8H)-qui-
nazolino[4,3-b]quinazolin-8-one and 6-alkyl-(13H)-quinazolino[3,4-a]quinazolin-13-one, respectively
was described for the first time. The differences in the IR and carbon NMR data of these isomeric fused qui-
nazolinoquinazolinones afford a useful method for distinguishing between the two series.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 30 January 2012
Revised 14 March 2012
Accepted 18 March 2012
Available online 23 March 2012
Keywords:
Nitrogen heterocycles
Cyclisation
Fused quinazolinoquinazolinones
Spectroscopic identification
Over the past decade, synthesis of the heterocyclic compounds
has become the cornerstone of synthetic organic chemistry as a re-
sult of wide variety of their application in medicinal and pharma-
ceutical chemistry.1 The exploration of heterocycles as privileged
structures in drug discovery is the important major area in medic-
inal chemistry.2 Among them, quinazoline ring system is an ubiqui-
tous structural unit and important pharmacophore found in a
number of alkaloids and many biologically active compounds.3
The synthesis of quinazolin-4(3H)-ones has been extensively inves-
tigated,4 as some of the members, for example, 4-anilinoquinazo-
lines, are shown to possess EGFR (epidermal growth factor
receptor) tyrosine kinase inhibitory effects, useful to inhibit tumour
growth.5 For example, IressaÒ and TarcevaÒ are the two selective
EGFR-TK inhibitors approved by the FDA in 2004 for locally ad-
vanced or metastatic non-small cell lung cancer (NSCLC) therapy
and are currently under clinical trials. (8H)-Quinazolino[4,3-b]qui-
nazolin-8-ones (1) and (13H)-quinazolino[3,4-a]quinazolin-13-
ones (2) are two isomeric angularly fused quinazolinoquinazoli-
nones. Although there are a few synthetic methods6–9 reported
for the synthesis of 1, there are only two articles10,11 in the litera-
ture for 2. Ozaki and co-workers10a employed a benzoxazine as
the key intermediate, whereas Marinho et al.10b used o-aminoben-
zonitrile as the starting material. In view of the important biological
activities of the fused quinazolinones, we have investigated the
synthesis and spectroscopic differentiation of the two systems 1
and 2, and herein we present our results.
Cyclisation of 2-(2-aminophenyl)quinazolin-4(3H)-one (3) with
triethyl orthoformate12 and auto-redox based cyclisation of
2-(2-nitrophenyl)quinazolin-4(3H)-one with tin(II) chloride in
the presence of alcohols13 on to N3-nitrogen to give (8H)-quinazo-
lino[4,3-b]quinazolin-8-ones (1) and 5,6-dihydro-quinazolino[4,3-
b]quinazolin-8-ones, respectively, via path a, are well established.
However, the cyclisation of 3 through path b, that is, on to the
N1-nitrogen for the generation of 2 is not reported in the literature
(Scheme 1). The selective formation of 1 from 3, via path a, is sur-
prising, and prompted us to re-examine the reaction employing
different reagents and conditions. The required 2-(2-aminophe-
nyl)quinazolin-4(3H)-one 3 was obtained from 2-aminobenzamide
and 2-nitrobenzoic acid in three steps.13,14 Compound 3 was then
treated with various reagents and the results are summarised in
Table 1.
First, the reaction was examined with one-carbon equivalent
reagents such as dimethylformamide–dimethylacetal (DMF–
DMA), triethyl orthoformate, formic acid and ethyl formate, which
resulted in the formation of only compound 1 (Table 1, entries 1–7)
as reported earlier.12 The structure of 1 has been established from
the spectroscopic data and confirmed by comparing with that de-
scribed in the literature.8 In a similar manner, reaction with the
two-carbon equivalent reagent such as triethyl orthoacetate, pro-
ceeded selectively through path a, and resulted in compound 1 in
q
Laila Communication #97.
⇑
Corresponding author. Tel.: +91 866 2546185; fax: +91 866 2546216.
E-mail addresses: somepalli01@rediffmail.com, drvsomepalli@gmail.com
(S. Venkateswarlu).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.03.055

2644
S. Venkateswarlu et al. / Tetrahedron Letters 53 (2012) 2643–2646
Table 1
O
8
Reaction of 3 with various reagentsa
9
6
7
5
10
11
Yieldb (%)
N
N
Entry
Reagent
Solvent/catalyst
Conditions
1
2
4
3
N
a
O
12
13
1
2
3
4
5
6
7
8
DMF–DMA
DMF–DMA
CH(OEt)3
CH(OEt)3
HCOOH
Toluene/AcOH
Toluene/AcOH
Toluene/AcOH
Toluene/AcOH
Toluene
HCOOH
HCOOEt
Toluene/AcOH
Toluene/AcOH
AcOH
rt, 30 min
Reflux, 10 min
rt, 24 h
Reflux, 2 h
rt, 24 h
Reflux, 30 min
Reflux, 24 h
rt, 1.5 h
Reflux, 15 min
rt, 16 h
91
86
50
90
—
82
86
91
91
—
—
—
—
—
—
a
h
1
t
1
a
p
NH NH2
3
2
1
O
N
p
a
1
t
13
h
HCOOH
b
12
2
3
N
HCOOEt
H3CC(OEt)3
H3CC(OEt)3
AcOH
AcOH
Ac2O
—
—
—
—
b
11
8
3
10
9
N
9
5
4
10
11
12
13
14
6
N
7
AcOH
Ac2O
Ac2O/pyridine
(C2H5CO)2O
Reflux, 4 h
Reflux, 2 h
Reflux, 2 h
Reflux, 2 h
—
—
2
49
50
55
32
29
23
Ac2O
(C2H5CO)2O
Scheme 1. Cyclisation of 3 via paths a and b.
a
All the reactions were performed with 3 (10 mmol), reagent (20 mmol) and
optionally acid or base.
91% yield (entries 8, 9), although no product was formed with ace-
tic acid (entries 10, 11). Contrary to these results, we were pleased
to observe that with acetic anhydride, the reaction proceeded to
give both the compounds 1 and 2 in good yield (entries 12, 13).15
Similarly with three-carbon equivalent reagent such as propionic
anhydride also gave two isomeric fused quinazolinoquinazolinones
1 and 2 (entry 14). To the best of our knowledge, this is the first re-
port on the formation of isomeric angular fused quinazolinoqui-
nazolinones 1 and 2 by the competitive cyclisation of 2-(2-
aminophenyl)quinazolin-4(3H)-one 3.
b
Isolated yields.
fused quinazolinoquinazolinones 1a–f and 2a–f, which were sepa-
rated by column chromatography on silica gel. The yield of com-
pounds 1a–f is found to be more (49–56%) than the
corresponding isomeric compounds 2a–f (20–32%) indicating that
the cyclisation on to N3-nitrogen is more favourable, which might
be due to better stability of system 1 (having complete p-conjuga-
tion from the carbonyl group to the carbon-6, which is absent in 2).
All the products have been characterized by their analytical and
spectroscopic data.16 The carbonyl absorptions in IR spectra of the
isomeric fused quinazolinoquinazolinones 1 and 2 are presented
in Table 2. It was found that the two compounds can easily be dif-
ferentiated by the carbonyl absorption band in IR spectra; the value
of 1 is between 1699 and 1709 cmÀ1 and 2 is between 1647 and
1660 cmÀ1. Similarly, the chemical shift of the carbonyl carbon in
the 13C NMR spectrum (Table 3) was also found to be diagnostic.
The value of 1 is in the range of d 160.2–161.6 ppm and the corre-
sponding carbon in 2 is in the range of d 166.0–167.5 ppm.
Encouraged by these results, generality of the reaction was
investigated with various 2-(2-aminophenyl)quinazolin-4(3H)-
ones (3) with acetic anhydride as the reagent. The substituted
derivatives of 3 were prepared from the corresponding 2-aminob-
enzamides and 2-nitrobenzoic acids as depicted in Scheme 2.
Thus, the reaction of 2-aminobenzamides with 2-nitrobenzoyl
chlorides in the presence of triethylamine gave 2-[(2-nitro-
phenyl)carbonylamino]benzamides 4. Ring closure of the com-
pounds 4 using aqueous potassium hydroxide in ethanol provided
2-(2-nitrophenyl)quinazolin-4(3H)-ones 513,14 in good yields. The
nitro functionality was then reduced using iron powder to generate
the key intermediates 3. Refluxing a solution of the compounds 3 in
acetic anhydride furnished a mixture of the isomeric angularly
A tentative mechanism is given in Scheme 3. First step is the
formation of RNHCOCH3 derivative 6. Intramolecular nucleophilic
O
R1
R2
CONH2
NH2
R1
R1
R2
CONH2
NH NO2
O
NO2
a
b
c
R2
N
77-85%
N
H
79-92%
83-90%
R3
R3
5
4
R4
R4
O
O
N
O
R5
R1
R2
R1
R2
R1
R2
N
N
NH NH2
N
N
d
+
R4
R3
N
N
72-81%
R5
R3
R3
3
R4
R4
1
2
(49-56%)
(20-32%)
a: R1=R2=R3=R4=H, R5=CH3
b: R1=R2=OCH3, R3=R4=H, R5=CH3
c: R1=R2=H, R3=R4=OCH3, R5=CH3
d: R1=R3=R4=H, R2=Cl, R5=CH3
e: R1=Br, R2=R3=R4=H, R5=CH3
f: R1=R2=R3=R4=H, R5=C2H5
Scheme 2. Reagents and conditions: (a) 2-nitrobenzoic acids, SOCl2, reflux, 2 h; THF, NEt3, rt, 2 h; (b) 10% aq KOH, EtOH, reflux, 30 min; (c) Fe/AcOH, 60–70 °C, 1 h; (d) Ac2O,
reflux, 2 h.

S. Venkateswarlu et al. / Tetrahedron Letters 53 (2012) 2643–2646
2645
Table 2
Organic Chemistry, Indian Institute of Science, Bangalore, India for
helpful discussions.
C@O absorption band of the compounds 1 and 2
Compd No.
C@O (
m
max/cmÀ1
)
References and notes
1
2
a
b
c
d
e
f
1701
1699
1700
1709
1701
1709
1660
1651
1647
1651
1655
1658
1. (a) Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V. Comprehensive Heterocyclic
Chemistry II; Pergamon: Oxford, 1996; (b) Joule, J. A.; Mills, K. Heterocyclic
Chemistry; Blackwell Science: Oxford, 2000.
2. (a) Nicolaou, K. C.; Vourloumis, D.; Winssinger, N.; Baran, P. S. Angew. Chem.,
Int. Ed. 2000, 39, 44–122; (b) Arya, P.; Chou, D. T. H.; Baek, M.-G. Angew. Chem.,
Int. Ed. 2001, 40, 339–346.
3. (a) Michael, J. P. Nat. Prod. Rep. 2001, 18, 543–559; (b) Reddy, P. S.; Reddy, P. P.;
Vasantha, T. Heterocycles 2003, 60, 183–226; (c) Horton, D. A.; Bourne, G. T.;
Smythe, M. L. Chem. Rev. 2003, 103, 893–930.
4. (a) Connolly, D. J.; Cusack, D.; O’Sullivan, T. P.; Guiry, P. J. Tetrahedron 2005, 61,
10153–10202; (b) Mhaske, S. B.; Argade, N. P. J. Org. Chem. 2004, 69, 4563–
4566; (c) Ahmed, K.; Reddy, K. S.; Prasad, B. R.; Babu, A. H.; Ramana, A. V.
Tetrahedron Lett. 2004, 45, 6517–6521; (d) Takeuchi, H.; Hagiwara, S.; Eguchi, S.
Tetrahedron 1989, 45, 6375–6386; (e) Li, F.; Feng, Y.; Meng, Q.; Li, W.; Li, Z.;
Wang, Q.; Tao, F. ARKIVOC 2007, 1, 40–50; (f) Gupton, J. T.; Correia, K. F.; Hertel,
G. R. Synth. Commun. 1984, 14, 1013–1025.
5. (a) Hennequin, L. F.; Thomas, A. P.; Johnstone, C.; Stokes, E. S. E.; Ple, P. A.;
Lohmann, J.-J. M.; Ogilvie, D. J.; Dukes, M.; Wedge, S. R.; Curwen, J. O.; Kendrew,
J.; Brempt, C. L. J. Med. Chem. 1999, 42, 5369–5389; (b) Seijas, J. A.; Vazquez-
Tato, M. P.; Martinez, M. M. Tetrahedron Lett. 2000, 41, 2215–2217; (c)
Rewcastle, G. W.; Denny, W. A.; Bridges, A. J.; Zhou, H.; Cody, D. R.; McMichael,
A.; Fry, D. W. J. Med. Chem. 1995, 38, 3482–3487; (d) Wang, J.-Q.; Gao, M.;
Miller, K. D.; Sledge, G. W.; Zheng, Q.-H. Bioorg. Med. Chem. Lett. 2006, 16, 4102–
4106.
Table 3
13C NMR data of isomeric fused quinazolinones
Compd No.
C@O (d ppm)
1
2
a
b
c
d
e
f
161.4
160.5
161.6
160.8
160.2
161.4
167.3
167.0
167.4
166.5
166.0
167.5
6. Stephen, T.; Stephen, H. J. Chem. Soc. 1956, 4173–4177.
7. Butler, K.; Partridge, M. W.; Waite, J. A. J. Chem. Soc. 1960, 4970–4976.
8. Alexandre, F.-R.; Berecibar, A.; Wrigglesworth, R.; Besson, T. Tetrahedron 2003,
59, 1413–1419.
H
H3C
O
N
O
O H3C
OH
NH
9. Hu, Z.; Li, S.-d.; Hong, P.-z. ARKIVOC 2010, 9, 171–177.
N
NH
10. (a) Ozaki, K.-I.; Yamada, Y.; Oine, T. Chem. Pharm. Bull. 1984, 32, 2160–2164; (b)
Marinho, E.; Araujo, R.; Proenca, F. Tetrahedron 2010, 66, 8681–8689.
11. In addition, Calestani et al. reported the formation of compound 2 as a minor
product during the reaction of 2-[4-imino-2-thioxa-1,4-dihydro-3(2H)-
quinazolinyl]benzonitrile with Mn(OAc)3; Calestani, G.; Capella, L.; Leardini,
R.; Minozzi, M.; Nanni, D.; Papa, R.; Zanardi, G. Tetrahedron 2001, 57, 7221–
7233.
12. Azizian, J.; Mohammadi, A. A.; Karimi, A. R.; Mohammadizadeh, M. R. J. Chem.
Res. 2004, 435–437.
13. (a) Roy, A. D.; Subramanian, A.; Roy, R. J. Org. Chem. 2006, 71, 382–385; (b) Roy,
A. D.; Subramanian, A.; Mukhopadhyay, B.; Roy, R. Tetrahedron Lett. 2006, 47,
6857–6860.
14. (a) Waibel, M.; Hasserodt, J. Tetrahedron Lett. 2009, 50, 2767–2769; (b)
Hanusek, J.; Sedlak, M.; Simunek, P.; Sterba, V. Eur. J. Org. Chem. 2002, 1855–
1863; (c) Gardner, B.; Kanagasoorian, A. J. S.; Smyth, R. M.; Williams, A. J. Org.
Chem. 1994, 59, 6245–6250; (d) Kabri, Y.; Gellis, A.; Vanelle, P. Green Chem.
2009, 11, 201–208; (e) Wang, G.-W.; Miao, C.-B.; Kang, H. Bull. Chem. Soc. Jpn.
2006, 79, 1426–1430.
N
3
-H2O
1
N
N
H
O
O
N
O
N
N
-H2O
2
NH
H3C
HO
N
H
H3C
6
Scheme 3. Probable mechanism for the formation of 1 and 2.
15. General procedure for 1 and 2: A solution of 3 (500 mg) in acetic anhydride
(10 mL) was refluxed for 2 h and allowed to cool to rt. The solution was poured
into ice cold water and stirred for 10 min. The solution was extracted with
chloroform (3 Â 100 mL) and the combined layer was washed with water,
brine dried over sodium sulfate and filtered. The solution was evaporated and
the residue was chromatographed over silica gel column using chloroform/
methanol (95:5) as eluents to give the products.
addition of either nitrogen N3 or N1 in 6 on to the amide, followed
by the loss of water molecule generates 1 or 2, respectively.
In summary, we have described an approach for the synthesis of
isomeric angularly fused quinazolinoquinazolinones 1 and 2. With
acid anhydrides, 2-(2-aminophenyl)quinazolin-4(3H)-ones 3 were
competitively cyclised to generate 6-alkyl-(8H)-quinazolino[4,3-
b]quinazolin-8-ones 1 and 6-alkyl-(13H)-quinazolino[3,4-a]qui-
nazolin-13-ones 2, via intramolecular nucleophilic addition of
either N3-nitrogen or N1-nitrogen, respectively. The methodology
provides an entry for the isomeric angularly fused quinazolinones
from a common intermediate and can be useful for the creation of
libraries in a short time. The two series of compounds were found
to be easily distinguishable from their IR and 13C NMR data. The
carbonyl absorptions in IR spectra of 1 are at higher value (be-
tween 1699 and 1709 cmÀ1) than those of 2 (between 1647 and
1660 cmÀ1). The carbonyl absorption in carbon NMR spectra of 1
appeared at higher field and the value is lower than that of 2 (ca.
5–6 ppm).
16. Spectroscopic data—Compound 1a: Off-white color solid (49%), mp 180–182 °C
(Lit.12 mp 180–181 °C). IR (KBr)
m
max 1701, 1624, 1601, 1375, 1338, 1252, 1209,
1082, 1024 cmÀ1
;
1H NMR (400 MHz, CDCl3): d 8.75 (1H, d, J = 8.0 Hz), 8.35
(1H, d, J = 7.6 Hz), 7.79–7.86 (2H, m), 7.73 (1H, td, J = 7.6, 1.2 Hz), 7.67 (1H, d,
J = 7.6 Hz), 7.55 (1H, td, J = 7.5, 1.0 Hz), 7.49 (1H, td, J = 7.4, 1.2 Hz), 3.12 (3H, s);
13C NMR (100 MHz, CDCl3): d 161.4, 150.4, 146.7, 146.2, 142.2, 135.3, 133.4,
127.9, 127.5, 127.1, 126.9, 126.3, 126.1, 121.6, 120.7, 27.3; LC–MS (positive ion
mode): m/z 262 (M+H)+.
Compound 2a: Pale brown color solid (32%), mp 224–226 °C (Lit.10a mp 227–
230 °C). IR (KBr) mmax 1660, 1616, 1604, 1595, 1346, 1328, 1273, 1240, 1215,
1114, 1070, 1041, 771, 754 cmÀ1 1H NMR (400 MHz, CDCl3): d 8.72 (1H, dd,
;
J = 8.0, 0.8 Hz), 8.41 (1H, d, J = 7.6 Hz), 7.83 (1H, td, J = 7.6, 1.6 Hz), 7.74–7.76
(2H, m), 7.71 (1H, d, J = 8.0 Hz), 7.63–7.67 (1H, m), 7.58 (1H, td, J = 7.6, 1.2 Hz),
3.00 (3H, s); 13C NMR (100 MHz, CDCl3): d 167.3, 153.3, 148.2, 143.4, 136.8,
134.9, 131.9, 128.4, 128.2, 128.1, 126.8, 126.3, 123.1, 120.4, 119.9, 26.0; LC–MS
(positive ion mode): m/z 262 (M+H)+.
Compound 1b: Off-white color solid (50%), mp 228–230 °C. IR (KBr)
mmax 1699,
1620, 1597, 1396, 1292, 1242, 1126, 1080, 1006, 775 cmÀ1 1H NMR (400 MHz,
;
CDCl3): d 8.61 (1H, d, J = 8.0 Hz), 7.68 (1H, t, J = 7.4 Hz), 7.62 (1H, d, J = 7.6 Hz),
7.59 (1H, s), 7.50 (1H, t, J = 7.2 Hz), 7.11 (1H, s), 4.04 (3H, s), 4.00 (3H, s), 3.12
(3H, s); 13C NMR (100 MHz, CDCl3): d 160.5, 156.1, 150.4, 149.0, 145.3, 143.2,
142.0, 133.0, 127.8, 126.9, 125.7, 121.6, 113.8, 107.3, 106.2, 56.4, 56.3, 27.6;
LC–MS (positive ion mode): m/z 322 (M+H)+; HRMS-(EI) (m/z) (M+H)+ calcd for
Acknowledgments
We sincerely thank Sri G. Ganga Raju, Chairman, and Mr. G.
Rama Raju, Director, Laila Impex, for support and encouragement.
We are also thankful to Professor A. Srikrishna, the Department of
C
18H16N3O3 322.1192, found 322.1192.
Compound 2b: Off-white color solid (25%), mp 282–284 °C. IR (KBr)
1604, 1280, 1250, 1203, 1006, 763 cmÀ1 1H NMR (400 MHz, CDCl3): d 8.69
mmax 1651,
;

2646
S. Venkateswarlu et al. / Tetrahedron Letters 53 (2012) 2643–2646
(1H, d, J = 8.0 Hz), 7.80 (1H, t, J = 7.4 Hz), 7.76 (1H, s), 7.68 (1H, d, J = 8.0 Hz),
166.5, 153.6, 147.7, 143.3, 138.5, 137.6, 135.2, 130.0, 128.7, 128.3, 126.9, 126.4,
121.5, 120.4, 119.7, 26.0; LC–MS (positive ion mode): m/z 296, 298 (M+H)+;
HRMS-(EI) (m/z) (M+H)+ calcd for C16H11ClN3O 296.0591, found 296.0594.
7.56 (1H, t, J = 7.6 Hz), 7.15 (1H, s), 4.04 (3H, s), 4.03 (3H, s), 3.02 (3H, s); 13C
NMR (100 MHz, CDCl3): d 167.0, 152.5, 152.4, 149.6, 147.6, 143.1, 134.5, 131.7,
128.0, 126.6, 126.2, 119.9, 117.1, 108.0, 103.2, 56.5, 56.5, 26.4; LC–MS (positive
ion mode): m/z 322 (M+H)+; HRMS-(EI) (m/z) (M+H)+ calcd for C18H16N3O3
322.1192, found 322.1190.
Compound 1e: Colorless solid (56%), mp 190–192 °C. IR (KBr)
m
max 1701, 1624,
1334, 1253, 1141, 771 cmÀ1 1H NMR (400 MHz, CDCl3):
;
d 8.70 (1H, d,
J = 8.0 Hz), 8.45 (1H, d, J = 1.6 Hz), 7.88 (1H, dd, J = 8.4, 1.6 Hz), 7.74 (1H, t,
J = 7.2 Hz), 7.64–7.67 (2H, m), 7.55 (1H, t, J = 7.4 Hz), 3.10 (3H, s); 13C NMR
(100 MHz, CDCl3): d 160.2, 150.0, 146.5, 145.5, 142.2, 138.4, 133.6, 129.9,
128.8, 128.1, 127.0, 126.1, 121.9, 121.3, 119.6, 27.2; LC–MS (positive ion
mode): m/z 340, 342 (M+H)+; HRMS-(EI) (m/z) (M+H)+ calcd for C16H11BrN3O
340.0085, found 340.0082.
Compound 1c: Off-white color solid (50%), mp 238–240 °C. IR (KBr)
m
;
max 1700,
1631, 1601, 1392, 1288, 1253, 1230, 1157, 1022, 864, 771 cmÀ1
1H NMR
(400 MHz, CDCl3): d 8.29 (1H, d, J = 8.0 Hz), 8.05 (1H, s), 7.80 (1H, t, J = 7.4 Hz),
7.74 (1H, d, J = 8.0 Hz), 7.43 (1H, t, J = 7.4 Hz), 7.08 (1H, s), 4.09 (3H, s), 4.01 (3H,
s), 3.10 (3H, s); 13C NMR (100 MHz, CDCl3): d 161.6, 154.4, 149.7, 149.3, 147.1,
146.1, 138.3, 135.2, 127.5, 126.7, 125.6, 120.1, 114.8, 108.0, 105.8, 56.4, 56.3,
27.3; LC–MS (positive ion mode): m/z 322 (M+H)+; HRMS-(EI) (m/z) (M+Na)
calcd for C18H15N3O3Na 344.1011, found 344.1012.
Compound 2e: Off-white color solid (21%), mp 288–290 °C. IR (KBr)
mmax 1655,
1608, 1342, 1269, 1207, 1072, 771 cmÀ1 1H NMR (400 MHz, CDCl3): d 8.71
;
(1H, d, J = 8.0 Hz), 8.55 (1H, d, J = 1.6 Hz), 7.82–7.86 (2H, m), 7.72 (1H, d,
J = 8.0 Hz), 7.57–7.65 (2H, m), 2.98 (3H, s); 13C NMR (100 MHz, CDCl3): d 166.0,
153.5, 147.7, 143.5, 135.7, 135.2, 135.0, 131.1, 128.4, 126.9, 126.4, 124.5, 122.2,
122.0, 119.7, 26.0; LC–MS (positive ion mode): m/z 340, 342 (M+H)+; HRMS-
(EI) (m/z) (M+H)+ calcd for C16H11BrN3O 340.0085, found 340.0087.
Compound 2c: Pale brown color solid (23%), mp 292–294 °C. IR (KBr) mmax
1647, 1601, 1334, 1265, 1238, 1203, 1018, 979, 756 cmÀ1 1H NMR (400 MHz,
;
CDCl3): d 8.40 (1H, d, J = 8.0 Hz), 8.04 (1H, s), 7.71–7.77 (2H, m), 7.61–7.65 (1H,
m), 7.11 (1H, s), 4.05 (3H, s), 4.04 (3H, s), 3.00 (3H, s); 13C NMR (100 MHz,
CDCl3): d 167.4, 155.9, 152.8, 150.0, 147.2, 140.1, 136.8, 131.7, 128.4, 128.0,
123.1, 120.4, 113.3, 107.0, 105.9, 56.7, 56.4, 26.1; LC–MS (positive ion mode):
m/z 322 (M+H)+. HRMS-(EI) (m/z) (M+Na) calcd for C18H15N3O3Na 344.1011,
found 344.1009.
Compound 1f: Colorless solid (55%), mp 162–164 °C (Lit.12 mp 156–157 oC). IR
(KBr) mmax 1709, 1620, 1597, 1558, 1334, 1238, 1080, 763 cmÀ1 1H NMR
;
(400 MHz, CDCl3): d 8.73 (1H, d, J = 8.0 Hz), 8.34 (1H, d, J = 7.6 Hz), 7.77–7.84
(2H, m), 7.68–7.74 (2H, m), 7.54 (1H, t, J = 6.8 Hz), 7.48 (1H, t, J = 7.0 Hz), 3.51
(2H, q, J = 7.2 Hz), 1.42 (3H, t, J = 7.2 Hz); 13C NMR (100 MHz, CDCl3): d 161.4,
154.7, 146.8, 146.4, 142.3, 135.3, 133.4, 127.9, 127.5, 127.2, 127.0, 126.3, 126.1,
121.5, 120.9, 31.9, 12.4; LC–MS (positive ion mode): m/z 276 (M+H)+.
Compound 1d: Colorless solid (52%), mp 192–194 °C. IR (KBr)
mmax 1709, 1624,
1593, 1338, 1246, 1207, 1105, 925, 779 cmÀ1 1H NMR (400 MHz, CDCl3): d
;
8.64 (1H, d, J = 8.0 Hz), 8.21 (1H, d, J = 8.4 Hz), 7.70–7.74 (2H, m), 7.63 (1H, d,
J = 8.0 Hz), 7.52 (1H, t, J = 7.6 Hz), 7.38 (1H, d, J = 8.0 Hz), 3.08 (3H, s); 13C NMR
(100 MHz, CDCl3): d 160.8, 150.1, 147.6, 147.3, 142.4, 141.7, 133.8, 128.9,
128.0, 127.0, 126.9, 126.5, 126.2, 121.2, 119.0, 27.3; LC–MS (positive ion
mode): m/z 296, 298 (M+H)+; HRMS-(EI) (m/z) (M+H)+ calcd for C16H11ClN3O
296.0591, found 296.0591.
Compound 2f: Colorless solid (23%), mp 188–190 °C. IR (KBr)
mmax 1658, 1620,
1593, 1342, 1240, 1188, 760 cmÀ1 1H NMR (400 MHz, CDCl3): d 8.71 (1H, d,
;
J = 8.0 Hz), 8.39 (1H, d, J = 7.6 Hz), 7.83 (1H, t, J = 7.4 Hz), 7.69–7.75 (3H, m),
7.64 (1H, t, J = 7.2 Hz), 7.57 (1H, t, J = 7.4 Hz), 3.27 (2H, q, J = 7.2 Hz), 1.45 (3H, t,
J = 7.2 Hz); 13C NMR (100 MHz, CDCl3): d 167.5, 153.4, 153.0, 143.7, 136.8,
134.8, 131.8, 128.4, 128.1, 128.0, 126.8, 126.6, 123.3, 120.4, 119.9, 30.7, 13.0;
LC–MS (positive ion mode): m/z 276 (M+H)+; HRMS-(EI) (m/z) (M+Na) calcd for
Compound 2d: Off-white color solid (20%), mp 216–218 °C. IR (KBr)
mmax 1651,
1585, 1261, 1068, 1022, 771 cmÀ1 1H NMR (400 MHz, CDCl3): d 8.68 (1H, d,
;
J = 8.0 Hz), 8.33 (1H, d, J = 8.4 Hz), 7.84 (1H, t, J = 7.4 Hz), 7.76 (1H, br s), 7.70
C17H13N3ONa 298.0956, found 298.0957.
(1H, d, J = 8.0 Hz), 7.56–7.62 (2H, m), 3.00 (3H, s); 13C NMR (100 MHz, CDCl3): d