NIS-mediated regioselective amidation of indole with quinazolinone and pyrimidone

Article abstract of DOI:10.1039/c4ra02417f

A mild, metal-free condition was developed for the direct regioselective C2 amidation of indoles and pyrroles with quinazolinone and pyrimidone derivatives in intermolecular fashion, which led to novel indolyl/pyrrolyl quinazolinone and pyrimidone derivatives in moderate to good yields. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4ra02417f

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NIS-mediated regioselective amidation of indole
with quinazolinone and pyrimidone†
Cite this: RSC Adv., 2014, 4, 20136
*
Suman Kr Ghosh and Rajagopal Nagarajan
Received 31st January 2014
Accepted 3rd April 2014
A mild, metal-free condition was developed for the direct regioselective C2 amidation of indoles and
pyrroles with quinazolinone and pyrimidone derivatives in intermolecular fashion, which led to novel
indolyl/pyrrolyl quinazolinone and pyrimidone derivatives in moderate to good yields.
DOI: 10.1039/c4ra02417f
www.rsc.org/advances
biologically active natural products contain C–N amide linkage
at the C2 position of indole, such as asperazine and chetomin
Introduction
Indole1 and pyrrole2 structural motifs are considered as ‘privi-
leged’ skeletons in numerous biologically active natural prod-
ucts. Hence, there is continual interest among chemists for the
direct functionalization of indoles and pyrroles in regioselective
fashion.3 A large number of reports by various groups have
focused on forming C–C bonds regioselectively at C2 position of
indole4 as well as pyrrole;5 however, only few reports are avail-
able on formation of C–N bond at the C2 position. In most
cases, regioselective amination of indole has been achieved by
using metal or other harsh conditions by different research
groups.6 However, reports for C2 amination by using mild
conditions without metal are scarce. Recently, Huang's group
demonstrated C–N bond formation at indole C2 with azole in
the presence of iodine.7 However, regioselective amidation of
indole and pyrrole has always remained a challenge to the
scientic community. Very few reports regarding amidation at
C2 of indoles8 and pyrroles9 are available. Our group also
reported the palladium-catalysed Buchwald cross-coupling
reaction at the C2 position of indole.10 Very recently, Li's group
presented direct amidation on indole by using the CDC
process.11 However, to date, reports for metal-free direct ami-
dation at indole C2 are limited. In 2008, Baran's group reported
a C2 amidation in indole in an intramolecular fashion to
synthesize psychotrimine.12 Very recently, Ji and coworkers also
reported intramolecular amidation at the indole C2 with sul-
phonamides.13 Liang's group also described iodine-mediated
intermolecular amidation of N-protected indoles with tosyl-
benzenamine.14 However, to the best of our knowledge, there is
no report for metal-free direct C2 amidation of indole with
cyclic amides in an intermolecular manner to date. Numerous
(Fig. 1). Most of these natural products contain cyclic amide
linkage, but direct amidation with cyclic amides at the C2
position of indole still remains unexplored.
Quinazolinone15 and pyrimidones16 are very important
classes of heterocycles, due to their diverse range of biological
properties like anticancer, anti-inammatory, diuretic, anti-
convulsant, and antihypertensive properties. Studies have
shown that the functionalization of quinazolinone's amide N–H
with alkyl, aryl groups increases the activity of quinazolinone
motif.17 However, heterocycles like indoles, pyrroles and other
cyclic amides have not been explored elaborately as a func-
tionality to date.18 Thus, indolylquinazolinone product may
possess some novel biological activity, which can be further
explored. Therefore, in this letter, we wish to report a novel N-
iodosuccinimide-mediated protocol for direct C2 amidation of
indoles and pyrroles with cyclic amides like pyrimidone/qui-
nazolinone derivatives.
Results and discussion
To develop a metal-free condition for selective amidation in an
indole moiety, we began our study with the reaction of 3-
methylindole (1a; 1.1 equiv.) and quinazolinone (2a; 1.0 equiv.)
with an iodination source such as N-iodosuccinimide (NIS; 1.2
School of Chemistry, University of Hyderabad, Hyderabad-500046, India. E-mail:
rnsc@uohyd.ernet.in; Fax: +91-40-23012460
† Electronic supplementary information (ESI) available: Copies of 1H NMR and
13C NMR spectra and crystal data. CCDC 956409–956412. For ESI and
crystallographic data in CIF or other electronic format See DOI:
10.1039/c4ra02417f
Fig. 1 Naturally occurring indole and pyrrole alkaloids containing C–N
amide linkage.
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equiv.) in CH3CN solvent at room temperature. Aer 16 h, we like CuI, CuBr, DIB, KI in 10 mol%, led to no improvement of
were delighted to nd the desired product 3-(3-methyl-1H-indol- the reaction performance.
2-yl)-3H-quinazolin-4-one (3a) in 30% yield. The relative struc-
To verify the role of NIS, i.e., whether it was catalytic or
ture of compound 3a was determined by detailed spectroscopic stoichiometric, we carried out two reactions, in which NIS had
analysis and X-ray crystallographic study (Table 1). Next, to been used in 2 equiv. (entry 20) and 30 mol% (entry 21). The use
improve the yield of the desired product 3a, we screened a of catalytic amounts of NIS decreased the yield of the product,
variety of both polar and nonpolar solvents (entries 1–12). Polar whereas higher loading of NIS failed to furnish more than 70%
solvents such as CH3CN, THF, DMSO and EtOAc (entries 1–4) of the desired product.
gave only moderate yields of the desired product. Interestingly,
when CHCl3 was used as the solvent, which is relatively equiv. of quinazolinone 2a, with 1.1 equiv. of indole 1a, using
nonpolar in nature, the yield of 3a was 70% (entry 5). 1.2 equiv. of NIS in CHCl3 solvent at RT for 16 h was deemed to
From the summarized results in Table 1, the reaction of 1.0
As a result, we used nonpolar solvents like toluene, benzene, be the optimum condition (entry 5). With these optimized
p-xylene, but unfortunately they were inferior to CHCl3 in terms conditions in hand, the generality and scope of the reaction was
of yields (entries 6–8). Therefore, we assumed that chlorinated explored for a range of 3-substituted indole, as well as 1,3
solvents might give a better yield compared with CHCl3. Thus, disubstituted indole, with quinazolinone derivatives and pyr-
we used some chlorine-containing solvents like DCM, DCE and imidone (Scheme 1). A variety of functional groups such as
1,2-dichlorobenzene (entries 9–11); however, among them, only moderate electron-withdrawing and electron-releasing groups
DCE was able to give a maximum yield of 64%. Moreover, using in substituted indoles were well tolerated to give moderate to
water and neat-reaction conditions also failed to improve the good yield of indolylquinazolinone and indolylpyrimidone
yield (entries 12–13). Thus, considering CHCl3 as the optimized products (3a–n). When electron-donating substituents at indole
solvent, we varied other parameters. When N-bromosuccini- C3 were coupled with quinazolinones and pyrimidones, a good
mide (entry 14) was used instead of NIS, the yield decreased, yield of the corresponding products was obtained (3a,d).
whereas in the case of iodine (entry 15), the yield remained However, 6-bromoquinazolinone and benzoquinazolinone,
almost unaffected. Furthermore, the screening of co-catalysts which are electron decient, gave a lower yield of the product
(3b–c), whereas when methyl was substituted with a moderate
Table 1 Screening of reaction parametersa
Entry
Solvent
Reagent/catalyst
Co-catalystb
Yieldsc 3a [%]
1
2
3
4
5
6
7
8
CH3CN
THF
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NBS
I2
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
30
10
40
58
70
15
34
20
53
64
42
40
33
62
67
62
56
20
30
70
20
DMSO
EtOAc
CHCl3
Toluene
Benzene
p-Xylene
DCM
DCE
1,2-DCB
H2O
9
10
11
12
13
14
15
16
17
18
19
20d
21e
Neat
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
NIS
NIS
NIS
NIS
NIS
NIS
CuI
CuBr
DIB
KI
—
—
a
Unless otherwise specied, reaction was performed on 0.34 mmol
scale with 1a (1.1 equiv.), 2a (1.0 equiv.), reagent (1.2 equiv.) and
Scheme
1 Synthesis of indolylquinazolinone derivatives. Unless
b
otherwise specified, the reaction was performed on 0.68 mmol scale
with 1 (1.1 equiv.), 2 (1 equiv.), NIS (1.2 equiv.) in solvent (7 ml) at RT. [A]
Reaction time was 72 h. [B] Reaction time was 48 h. N.R. ¼ no reaction.
solvent (5 ml) at RT. The reaction time was 16 h. Co-catalyst used 10
c
d
e
mol%. Isolated yields. NIS used was 2 equiv. NIS used was 30
mol%.
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electron-withdrawing group like CH2CO2Me, the yields of the regioselective C–N bond formation at the pyrrole C2 were
corresponding products remained almost unaffected (3f–g). limited, we executed our optimized condition over the pyrrole
Surprisingly, when the aldehyde group was placed at C3 of and quinazolinone moiety. Unfortunately, the reaction failed to
indoles, the reaction did not proceed even aer three days (3h). give the desired pyrrolylquinazolinone product aer 48 h of
Aer examining electron-donating as well as electron-with- stirring at room temperature. Next, we replaced NIS with gran-
drawing groups in C3 position of indoles, we tested the feasi- ular iodine in our optimized condition. To our delight, we
bility of the reaction with 1,3-disubstituted indoles. We found obtained 38% of the desired product aer 12 h.
that substituent like methyl and benzyl groups on nitrogen were
Hence, we again sought for an optimum condition with
well tolerated (3i–m). It is worth mentioning that 1,3-dimethy- iodine and different solvents, and it was determined that iodine
lindole gave a better yield with the corresponding indolylqui- is the key component for this reaction to occur. The optimized
nazolinone product compared with the 3-methylindole. When conditions (1.1 equiv. of 6, 1.3 equiv. of I2, CHCl3, RT, 18 h) were
the indole nitrogen was protected with an electron-withdrawing found to be applicable over a range of N-substituted/unsub-
group, Boc, the reaction did not proceed even aer 48 h (3n). stituted pyrrole and quinazolinone derivatives (Scheme 3).
This may be due to the lowering of nucleophilicity on the indole N-substituted/unsubstituted pyrroles reacted smoothly with
nitrogen, which plays a vital role in iodination. Subsequently, quinazolinone derivatives to give corresponding pyrroloquina-
we expanded the scope of the reaction with the C3 unsub- zolinone products (7a–d) in moderate yields (Scheme 3).
stituted indoles and applied our optimized condition on plain
Furthermore, we were eager to see the outcome of the reac-
indoles and quinazolinones. The outcome of this reaction, tion when aliphatic amides/imides were employed as a coupling
which gave the expected product 5a, was not surprising; partner with 3-methylindole. Hence, we took 3-methylindole
however, along with the product a lower percentage of 3- (1.1 equiv.), benzamide (1.0 equiv.), and NBS (1.1 equiv.) at
iodoindolylquinazolinone (5aa) was also obtained. We sus- room temperature in CHCl3, and an unexpected product, 3-
pected that the variation in the amount of NIS may give one of methyl-1,3-dihydro-indol-2-one (8), was formed in 50% yield
the products specically. Thus, we took indoles and quinazoli- aer 4 h (Scheme 4[A]). Next, 3-methylindole (1.1 equiv.) was
nones as the coupling products and used only 1.05 equiv. of NIS treated with benzanilide (1.0 equiv.) and NIS (1.1 equiv.) in
instead of 1.2 equiv. under the same optimized conditions. Aer CHCl3. Again, we obtained another undesired product, 3,30-
16 h, we obtained 3-(1H-indol-2-yl)-3H-quinazolin-4-one (5a), dimethyl-30H-[1,20]biindolyl-30-ol (9), in 22% yield aer 24 h.
whereas when 1.7 equiv. of the NIS was used, the reaction gave This unexpected compound (9) was fully characterized with
only 3-(3-iodo-1H-indol-2-yl)-3H-quinazolin-4-one (5aa) speci- NMR spectral data along with the X-ray crystallographic study.
cally (Fig. 2).
Synthesis of this kind of dimer is already reported in the liter-
Furthermore, this reaction also tolerated 5- and 6-bro- ature using Co-salen complex in the oxygen atmosphere.19 It
moindoles and 5-methoxyindole, as well as afforded the tar-
geted product along with the undesired iodo-substituted
product. The yields of both products depended on the amount
of the NIS and the time of the reaction. The 1H NMR clearly
showed the variation in yield between the desired indolylqui-
nazolinone and the undesired 3-iodoindolylquinazolinone
products (see ESI†). Surprisingly, when 1-methylindole and 1-
butylindoles reacted with quinazolinone, we obtained only our
desired products (5f–g), whereas 1-sulfonylindole and 7-azain-
dole were inactive in this procedure. The reason behind this
observation may be again justied by the lowering and
increasing of the nucleophilicity of the indole nitrogen,
depending upon the electron-withdrawing/releasing group
(Scheme 2).
Aer a successful encounter with indoles, we further
extended the scope to pyrrole heterocycle. Because reports for
Scheme 2 Synthesis of 3-unsubstituted indolylquinazolinone deriva-
tives. Unless otherwise specified, the reaction was performed on 0.68
mmol scale with 4 (1.1 equiv.), 2a (1 equiv.), NIS (1.2 equiv.) in solvent (7
Fig. 2 ORTEP of Compound 3i, 5aa (hydrogens are removed for ml) at RT. [A] 1.05 equiv. of NIS was used, and reaction time 16 h. [B] 1.7
clarity).
equiv. of NIS was used, and reaction time was 24 h. N.R. ¼ no reaction.
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succinimide coupled to the 1,3-dimethylindole (Scheme 4[C]).
The lower yield for the formation of 1-(1,3-dimethyl-1H-indol-2-
yl)-pyrrolidine-2,5-dione (10) can be justied by the in situ
formation of succinimide. Next, when succinimide was used as
a starting material, the yield of the coupled product (10)
increased to 62% (Scheme 4[D]); however, the use of phthali-
mide as a starting material also furnished only a succinimide-
coupled product (10) (Scheme 4[E]). This may be due to the
iminol form, rather than the amide form, which is participating
in the reaction as shown in mechanism (Scheme 5).
Aer all of these extensive studies with a variety of
substrates, and from the outcomes we proposed a possible
pathway of the reaction as shown in Scheme 5. Iodination on C3
of indole with NIS produces the intermediate 11, which
undergoes an immediate nucleophilic substitution with the
iminol form (12) to generate the intermediate 13. Then,
subsequent elimination of HI led to the expected product (14)
(Scheme 5).
Scheme 3 Synthesis of pyrrolylquinazolinone derivatives. Reaction
was performed on 0.68 mmol scale with 6 (1.1 equiv.), 2 (1 equiv.), I2
(1.3 equiv.) in solvent (7 ml) at RT.
In the nal part of our study, we synthesised an indolo [1,3]-
diazepine skeleton fused with quinazolinone. Diazepines are a
very important class of heterocycles having considerable
applications in pharmaceutical industry. However, among
them, 1,4-diazepine has the maximum applications, whereas,
1,3-diazepine systems are very rarely known because of their
biological activity. Some 1,3-diazepine-fused heterocycles show
anticancer and anti-AIDS activity as well as inhibition of HIV
protease.20 Thus, we synthesised a 1,3-diazpine containing a
novel indolylquinazolinone heterocycle, which may possess
some interesting biological properties. We took compound 3a
and treated with 1,3-dibromopropane in the presence of K2CO3
and DMF solvent at room temperature, which led to the
formation of 3-[1-(3-bromo-propyl)-3-methyl-1H-indol-2-yl]-3H-
quinazolin-4-one (15). Next, the treatment of compound 15 with
LDA in presence of HMPA at ꢀ78 ꢁC furnished the desired
macrocyclic compound 16 in 42% yields (Scheme 6).
Scheme 4 Reaction between indoles and aliphatic amides/imides. [A]
1a (0.98 mmol), benzamide (0.82 mmol) and NBS (0.98 mmol) in a
solvent at RT for 4 h. [B] 1a (0.51 mmol), benzanilide (0.51 mmol), NIS
(0.61 mmol) in a solvent at RT for 24 h. [C] 1i (0.35 mmol), benzanilide
(0.35 mmol), NIS (0.35 mmol) in a solvent at RT for 24 h. [D] 1i (1 mmol),
succinimide (1 mmol), NIS (1 mmol) in a solvent at RT for 24 h. [E] 1i
(0.68 mmol), phthalimide (0.68 mmol), NIS (0.82 mmol) in a solvent at
RT for 24 h.
Scheme 5 Possible mechanism.
may be that the indole nitrogen is more nucleophilic, in
comparison with the nitrogen of benzanilide, which led to the
formation of the unexpected product (9). Thus, we suspected
that protection of the indole nitrogen would be able to furnish
our expected coupled product. Therefore, we used the same
reaction condition with 1,3-dimethylindole. However, this time
we obtained a coupled product, but instead of benzanilide,
Scheme 6 Synthesis of the indolo [1,3]-diazepine skeleton.
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C
C
17H12Br79N3O (M
+
H) 354.0242, found 354.0240;
Conclusions
17H12Br81N3O (M + H) 356.0222, found 354.0219.
3-(3-Methyl-1H-indol-2-yl)-3H-pyrimidin-4-one (3d). Compound
In summary, we have developed an efficient, metal-free meth-
odology for direct amidation regioselectively at C2 in indoles
and pyrroles with quinazolinones and pyrimidones. A series of
novel indolylquniazolinones/pyrimidones and pyrrolylquina-
zolinones were prepared with free or protected indoles and
pyrroles. Further, we prepared a highly functionalized 1,3-dia-
zepine compound, which may have useful biological properties.
ꢁ
was obtained as grayish solid (102 mg, 67%); m.p. ¼ 138 C; IR
(KBr) 3336, 3063, 1671, 1589, 1221, 991, 750 cmꢀ1; 1H NMR (400
MHz, DMSO-d6) d 11.50 (1H, s), 8.52 (1H, s), 8.04 (1H, dd, J ¼ 6.4
Hz, J ¼ 2.0 Hz), 7.58 (1H, d, J ¼ 8.0 Hz), 7.38 (1H, dd, J ¼ 8.0 Hz, J ¼
0.8 Hz), 7.22–7.18 (1H, m), 7.11–7.07 (1H, m), 6.60 (1H, dd, J ¼ 6.0
Hz, J ¼ 0.8 Hz), 2.11 (3H, s); 13C NMR (100 MHz, DMSO-d6) d 160.3,
154.3, 153.3, 134.3, 127.6, 127.4, 123.1, 119.6, 119.5, 116.2, 111.9,
106.2, 8.0; HRMS (ESI-MS) calcd for C13H11N3O (M + H) 226.0980,
found 226.0980.
Experimental
General experimental procedure for preparation of
[2-(4-Oxo-4a,8a-dihydro-4H-quinazolin-3-yl)-1H-indol-3-yl]-
acetic acid methyl ester (3e). Compound was obtained as light
indolylquinazolinone
An oven dried Schlenk tube was charged with indole or its yellow solid (163 mg, 72%); m.p. ¼ 102 ꢁC; IR (KBr) 3260, 2926,
derivative (1, 0.74 mmol), quinazolinone derivatives (2, 0.68 1731, 1676, 1605, 1276, 975, 739 cmꢀ1 1H NMR (500 MHz,
;
mmol), NIS (0.81 mmol) and distilled CHCl3 (7 ml). The Schlenk DMSO-d6) d 11.76 (1H, s), 8.35 (1H, s), 8.25 (1H, dd, J ¼ 8.0 Hz,
tube was then ushed with nitrogen. The reaction mixture was J ¼ 1.0 Hz), 7.96–7.92 (1H, m), 7.80 (1H, d, J ¼ 8.0 Hz), 7.67–
stirred at RT for 16 h. It was then diluted with water, and the 7.64 (1H, m), 7.62 (1H, d, J ¼ 8.0 Hz), 7.43 (1H, d, J ¼ 8.5 Hz),
aqueous phase was extracted with DCM (30 ml). The combined 7.26–7.22 (1H, m), 7.14–7.11 (1H, m), 3.72 (2H, s), 3.50 (3H, s);
organic layer was dried over Na2SO4 and concentrated using a 13C NMR (125 MHz, DMSO-d6) d 171.6, 160.4, 147.9, 147.6,
rotary evaporator under reduced pressure. The resulting residue 135.6, 134.1, 129.2, 128.3, 128.0, 127.0, 126.8, 123.2, 122.1,
was puried by column chromatography on silica gel (ethyl 120.0, 119.6, 112.1, 104.2, 52.1, 29.3; HRMS (ESI-MS) calcd for
acetate–hexane ¼ 3 : 7) to afford the desired product.
C
19H15N3O3 (M + H) 334.1192, found 334.1187.
[2-(4-Oxo-4a,10a-dihydro-4H-benzo[g]quinazolin-3-yl)-1H-indol-
3-(3-Methyl-1H-indol-2-yl)-4a,8a-dihydro-3H-quinazolin-4-one
(3a). Compound was obtained as yellow solid (131 mg, 70%); 3-yl]-acetic acid methyl ester (3f). Compound was obtained as
m.p. ¼ 222 ꢁC; IR (KBr) 3274, 2921, 2853, 1708, 1662, 1600, 1257, yellow solid (150 mg, 58%); m.p. ¼ 106 ꢁC; IR (KBr) 3441, 3046,
1
1014, 738 cmꢀ1; H NMR (400 MHz, DMSO-d6) d 11.48 (1H, s), 1731, 1676, 1276, 745 cmꢀ1
;
1H NMR (500 MHz, DMSO-d6) d
8.40 (1H, s), 8.24 (1H, d, J ¼ 7.6 Hz), 7.93 (1H, t, J ¼ 7.2 Hz), 7.79 11.79 (1H, s), 9.00 (1H, s), 8.38 (1H, s), 8.32 (1H, s), 8.30 (1H, d, J
(1H, d, J ¼ 8.0 Hz), 7.64 (1H, t, J ¼ 7.2 Hz), 7.59 (1H, d, J ¼ 7.6 Hz), ¼ 8.0 Hz), 8.20 (1H, d, J ¼ 8.5 Hz), 7.76–7.73 (1H, m), 7.68–7.62
7.38 (1H, d, J ¼ 8.0 Hz), 7.20 (1H, t, J ¼ 7.2 Hz), 7.09 (1H, t, J ¼ 7.2 (2H, m), 7.44 (1H, d, J ¼ 8.0 Hz), 7.26–7.23 (1H, m), 7.15–7.12
Hz), 2.14 (3H, s); 13C NMR (100 MHz, DMSO-d6) d 160.5, 147.9, (1H, m), 3.75 (2H, s), 3.50 (3H, s); 13C NMR (125 MHz, DMSO-d6)
135.6, 134.3, 128.3, 128.0, 127.5, 127.0, 122.9, 122.1, 119.5, 119.5, d 171.6, 160.9, 146.6, 143.2, 136.7, 134.1, 131.9, 129.9, 129.5,
111.8, 106.4, 8.1; HRMS (ESI-MS) calcd for C17H13N3O (M + H) 129.4, 128.8, 128.5, 127.4, 126.9, 125.8, 123.1, 120.90, 119.99,
276.1137, found 276.1139.
119.6, 112.1, 104.2, 52.1, 29.4; HRMS (ESI-MS) calcd for
3-(3-Methyl-1H-indol-2-yl)-4a,10a-dihydro-3H-benzo[g]qui-
nazolin-4-one (3b). Compound was obtained as pale yellow
C
23H17N3O3 (M + H) 384.1348, found 384.1349.
[2-(6-Oxo-6H-pyrimidin-1-yl)-1H-indol-3-yl]-acetic
acid
solid (115 mg, 52%); m.p. ¼ 228 ꢁC; IR (KBr) 3271, 2920, 1671, methyl ester (3g). Compound was obtained as red solid (125 mg,
1605, 1265, 739, 706 cmꢀ1
;
1H NMR (500 MHz, DMSO-d6) d 65%); m.p. ¼ 92 ꢁC; IR (KBr) 3221, 2947, 1736, 1698, 1600, 1238,
11.51 (1H, s), 9.00 (1H, s), 8.39 (1H, s), 8.38 (1H, s), 8.30 (1H, d, 827, 761 cmꢀ1; H NMR (400 MHz, DMSO-d6) d 11.78 (1H, s),
J ¼ 8.0 Hz), 8.20 (1H, d, J ¼ 8.5 Hz), 7.76–7.73 (1H, m), 7.68– 8.46 (1H, s), 8.03 (1H, dd, J ¼ 8.8 Hz, J ¼ 2.0 Hz), 7.60 (1H, d, J ¼
7.65 (1H, m), 7.61 (1H, d, J ¼ 7.5 Hz), 7.40 (1H, d, J ¼ 8.5 Hz), 7.6 Hz), 7.40 (1H, d, J ¼ 8.0 Hz), 7.22 (1H, t, J ¼ 8.0 Hz), 7.11 (1H,
7.24–7.20 (1H, m), 7.13–7.10 (1H, m), 2.18 (3H, s); 13C NMR t, J ¼ 8.0 Hz), 6.58 (1H, d, J ¼ 6.8 Hz), 3.65 (2H, s), 3.52 (3H, s);
(125 MHz, DMSO-d6) d 160.9, 146.9, 143.3, 136.7, 134.3, 131.9, 13C NMR (100 MHz, DMSO-d6) d 171.5, 160.1, 154.2, 152.9,
129.9, 129.5, 128.8, 128.5, 128.2, 127.5, 127.4, 125.8, 122.9, 134.1, 128.7, 126.7, 123.3, 120.0, 119.6, 116.2, 112.1, 103.9, 52.2,
120.9, 119.5, 119.4, 111.8, 106.4, 8.1; HRMS (ESI-MS) calcd for 29.3; HRMS (ESI-MS) calcd for C15H13N3O3 (M + H) 284.1035,
1
C
21H15N3O (M + H) 326.1293, found 326.1294.
found 284.1031.
6-Bromo-3-(3-methyl-1H-indol-2-yl)-4a,8a-dihydro-3H-quina-
3-(1,3-Dimethyl-1H-indol-2-yl)-4a,8a-dihydro-3H-quinazolin-
zolin-4-one (3c). Compound was obtained as yellow solid (120 4-one (3i). Compound was obtained as yellow solid (145 mg,
mg, 50%); m.p. ¼ 220 ꢁC; IR (KBr) 3276, 2958, 1665, 1600, 1265, 74%); m.p. ¼ 156 ꢁC; IR (KBr) 3068, 2920, 1693, 1605, 1249, 920,
1
832, 739 cmꢀ1; H NMR (500 MHz, DMSO-d6) d 11.48 (1H, s), 750 cmꢀ1; 1H NMR (500 MHz, DMSO-d6) d 8.37 (1H, s), 8.26 (1H,
8.47 (1H, s), 8.33 (1H, d, J ¼ 2.5 Hz), 8.10 (1H, dd, J ¼ 8.5 Hz, J ¼ dd, J ¼ 8.0 Hz, J ¼ 1.0 Hz), 7.98–7.94 (1H, m), 7.82 (1H, d, J ¼ 8.0
2.5 Hz), 7.76 (1H, d, J ¼ 8.5 Hz), 7.60 (1H, d, J ¼ 8.0 Hz), 7.40 Hz), 7.68–7.65 (1H, m), 7.64 (1H, d, J ¼ 8.0 Hz), 7.52 (1H, d, J ¼
(1H, d, J ¼ 7.8 Hz), 7.23–7.20 (1H, m), 7.12–7.09 (1H, m), 2.15 8.5 Hz), 7.31–7.28 (1H, m), 7.15 (1H, t, J ¼ 8.0 Hz), 3.54 (3H, s),
(3H, s); 13C NMR (125 MHz, DMSO-d6) d 159.4, 148.6, 147.0, 2.14 (3H, s); 13C NMR (125 MHz, DMSO-d6) d 160.8, 148.1, 147.9,
138.4, 134.3, 130.5, 129.0, 127.7, 127.4, 123.7, 123.1, 120.8, 135.8, 135.3, 129.4, 128.4, 128.1, 127.1, 126.5, 123.2, 122.0,
119.6, 119.5, 111.9, 106.6, 8.1; HRMS (ESI-MS) calcd for
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119.8, 119.6, 110.4, 106.7, 29.6, 8.1; HRMS (ESI-MS) calcd for 8.0 Hz), 7.46 (1H, d, J ¼ 8.0 Hz), 7.20 (1H, t, J ¼ 8.0 Hz), 7.09 (1H,
C
18H15N3O (M + H) 290.1293 found 290.1291.
3-(1,3-Dimethyl-1H-indol-2-yl)-4a,10a-dihydro-3H-benzo[g] 147.7, 147.4, 135.6, 134.9, 131.9, 128.3, 127.9, 126.9, 122.7,
t, J ¼ 8.0 Hz), 6.69 (1H, s); 13C NMR (100 MHz, DMSO-d6) d 160.3,
quinazolin-4-one (3j). Compound was obtained as light yellow 121.9, 120.9, 120.2, 112.1, 98.1; HRMS (ESI-MS) calcd for
solid (137 mg, 60%); m.p. ¼ 164 ꢁC; IR (KBr) 3310, 2894, 1682,
C
16H11N3O (M + H) 262.0980, found 262.0981.
3-(3-Iodo-1H-indol-2-yl)-3H-quinazolin-4-one
1249, 942, 756 cmꢀ1; 1H NMR (400 MHz, DMSO-d6) d 8.99 (1H,
(5aa).
s), 8.39 (1H, s), 8.31 (1H, s), 8.27 (1H, d, J ¼ 8.4 Hz), 8.18 (1H, Compound was obtained as bright yellow solid; (144 mg, 55%);
d, J ¼ 8.4 Hz), 7.73 (1H, t, J ¼ 7.6 Hz), 7.66–7.62 (2H, m), 7.51 m.p. ¼ 205 ꢁC; IR (KBr) 3342, 3063, 1682, 1254, 904, 767 cmꢀ1
;
(1H, d, J ¼ 8.4 Hz), 7.28 (1H, t, J ¼ 7.6 Hz), 7.14 (1H, t, J ¼ 7.2 1H NMR (400 MHz, DMSO-d6) d 12.34 (1H, s), 8.42 (1H, s), 8.26
Hz), 3.56 (3H, s), 2.16 (3H, s); 13C NMR (100 MHz, DMSO-d6) d (1H, d, J ¼ 8.0 Hz), 7.96 (1H, t, J ¼ 8.0 Hz), 7.81 (1H, d, J ¼ 8.0
161.4, 146.9, 143.4, 136.8, 135.3, 131.9, 129.9, 129.6, 128.9, Hz), 7.67 (1H, t, J ¼ 7.2 Hz), 7.48 (1H, d, J ¼ 8.0 Hz), 7.39 (1H, d, J
128.5, 127.4, 126.5, 125.9, 123.1, 120.8, 119.8, 119.6, 110.4, ¼ 7.6 Hz), 7.30 (1H, t, J ¼ 7.2 Hz), 7.21 (1H, t, J ¼ 7.6 Hz); 13C
106.7, 29.6, 8.2; HRMS (ESI-MS) calcd for C22H17N3O (M + H) NMR (100 MHz, DMSO-d6) d 160.2, 147.9, 147.8, 136.0, 135.3,
340.1450, found 340.1450.
133.2, 129.3, 128.6, 128.2, 127.1, 124.2, 121.8, 121.2, 121.1,
112.8, 58.8; HRMS (ESI-MS) calcd for C16H10IN3O (M + H)
3-(1-Benzyl-3-methyl-1H-indol-2-yl)-4a,8a-dihydro-3H-quina-
zolin-4-one (3k). Compound was obtained as light grayish solid 387.9947, found 387.9946.
(169 mg, 68%); m.p. ¼ 106 ꢁC; IR (KBr) 3364, 3024, 2909, 1687,
3-(5-Methoxy-1H-indol-2-yl)-3H-quinazolin-4-one (5b)
3-(3-Iodo-5-methoxy-1H-indol-2-yl)-3H-quinazolin-4-one (5bb).
1610, 1249, 920, 739 cmꢀ1; 1H NMR (500 MHz, DMSO-d6) d 8.23
(1H, d, J ¼ 8.0 Hz), 8.14 (1H, s), 7.92 (1H, t, J ¼ 7.5 Hz), 7.74 (1H, Compounds were obtained as bright yellow solid mixture with
d, J ¼ 8.0 Hz), 7.68 (1H, d, J ¼ 8.0 Hz), 7.64 (1H, t, J ¼ 7.5 Hz), ratio of (5b : 5bb ¼ 1 : 0.41); (overall 108 mg, 45%); IR (KBr)
7.45 (1H, d, J ¼ 8.0 Hz), 7.24 (1H, t, J ¼ 7.5 Hz), 7.18–7.14 (4H, 3358, 3260, 2991, 2926, 1682, 1654, 1254, 1210, 767, 690 cmꢀ1
;
m), 6.96–6.94 (2H, m), 5.43 (1H, d, J ¼ 17 Hz), 5.05 (1H, d, J ¼ 17 1H NMR (400 MHz, DMSO-d6) d 12.20 (0.396H, s), 11.62 (1.00H,
Hz), 2.15 (3H, m). 13C NMR (125 MHz, DMSO-d6) d 160.8, 147.9, s), 8.46 (1.040H, s), 8.38 (0.443H, s), 8.25–8.23 (1.428H, m), 7.97–
147.7, 137.9, 135.7, 135.1, 129.2, 128.9, 128.4, 128.0, 127.7, 7.89 (1.433H, m), 7.82–7.76 (1.390H, m), 7.68–7.61 (1.392H, m),
127.1, 126.9, 126.7, 123.5, 121.9, 120.1, 119.9, 110.9, 107.9, 46.6, 7.39–7.32 (1.459H, m), 7.102 (1.063H, s), 6.94–6.92 (0.446H, m),
8.2; HRMS (ESI-MS) calcd for C24H19N3O (M + H) 366.1606, 6.84–6.82 (1.387H, m), 6.59 (0.978H, s), 3.81 (1.184H, s), 3.76
found 366.1606.
(2.961H, s); 13C NMR (100 MHz, DMSO-d6) d 160.3, 155.0, 154.2,
3-(1-Benzyl-3-methyl-1H-indol-2-yl)-4a,10a-dihydro-3H-benzo 147.7, 147.4, 135.6, 132.1, 129.9, 128.4, 127.9, 127.4, 126.9,
[g]quinazolin-4-one (3l). Compound was obtained as light yellow 121.9, 113.0, 112.9, 102.5, 97.9, 55.8; HRMS (ESI-MS) calcd for
solid (130 mg, 46%); m.p. ¼ 130 ꢁC; IR (KBr) 3052, 2920, 1687, 5b C17H13N3O2 (M + H) 292.1086, found 292.1079; for 5bb
1600, 1265, 898, 750 cmꢀ1; 1H NMR (400 MHz, DMSO-d6) d 8.96
(1H, s), 8.31 (1H, s), 8.27 (1H, d, J ¼ 8.4 Hz), 8.16 (1H, d, J ¼ 8.4
C
17H12IN3O2 (M + H) 418.0052, found 418.0051.
3-(5-Bromo-1H-indol-2-yl)-3H-quinazolin-4-one
(5c).
Hz), 8.08 (1H, s), 7.72 (1H, t, J ¼ 7.2 Hz), 7.68–7.62 (2H, m), 7.45 Compound was obtained as bright yellow solid (70 mg, 30%);
(1H, d, J ¼ 8.0 Hz), 7.30 (1H, d, J ¼ 6.4 Hz), 7.24 (1H, t, J ¼ 7.6 m.p. ¼ 188 ꢁC; IR (KBr) 3221, 2926, 1682, 1654, 904, 772 cmꢀ1
;
Hz), 7.17–7.14 (3H, m), 6.99–6.96 (2H, m), 5.45 (1H, d, J ¼ 16.8 1H NMR (400 MHz, DMSO-d6) d 12.03 (1H, s), 8.48 (1H, s), 8.25
Hz), 5.09 (1H, d, J ¼ 16.8 Hz), 2.17 (3H, s); 13C NMR (100 MHz, (1H, d, J ¼ 8.0 Hz), 7.92 (1H, t, J ¼ 7.6 Hz), 7.81 (1H, s), 7.77 (1H,
DMSO-d6) d 161.3, 146.6, 143.2, 138.1, 136.7, 135.1, 131.9, 129.9, d, J ¼ 8.0 Hz), 7.64 (1H, t, J ¼ 7.6 Hz), 7.42 (1H, d, J ¼ 8.8 Hz),
129.5, 129.3, 129.1, 128.9, 128.4, 127.7, 127.6, 127.4, 126.9, 7.30 (1H, d, J ¼ 8.8 Hz), 6.69 (1H, s); 13C NMR (100 MHz, DMSO-
126.8, 125.8, 123.4, 120.7, 120.0, 119.8, 110.9, 107.9, 46.61, 8.2; d6) d 160.2, 147.7, 147.2, 135.7, 133.5, 133.2, 128.8, 128.4, 128.0,
HRMS (ESI-MS) calcd for C28H21N3O (M + H) 416.1763, found 126.9, 125.3, 123.2, 121.8, 114.2, 112.6, 97.7; HRMS (ESI-MS)
416.1764.
3-(1-Benzyl-3-methyl-1H-indol-2-yl)-3H-pyrimidin-4-one (3m). C16H10Br81N3O (M + H) 342.0065, found 342.0085.
3-(5-Bromo-3-iodo-1H-indol-2-yl)-3H-quinazolin-4-one
calcd for C16H10Br79N3O (M + H) 340.0085, found 340.0082;
Compound was obtained as yellow solid (132 mg, 62%); m.p. ¼
(5cc).
102 ꢁC; IR (KBr) 3079, 2915, 1731, 1698, 1282, 843, 739 cmꢀ1; 1H Compound was obtained as bright yellow solid (111 mg, 35%);
NMR (400 MHz, DMSO-d6) d 8.22 (1H, s), 7.99 (1H, d, J ¼ 6.8 Hz), m.p. ¼ 218 ꢁC; IR (KBr) 3407, 2932, 1675, 1601, 1455, 1008, 938
7.66 (1H, d, J ¼ 7.6 Hz), 7.48 (1H, d, J ¼ 8.0 Hz), 7.26–7.13 (5H, cmꢀ1; 1H NMR (500 MHz, DMSO-d6) d 12.59 (1H, s), 8.43 (1H, s),
m), 6.97–6.95 (2H, m), 6.59 (1H, dd, J ¼ 6.8 Hz, J ¼ 0.8 Hz), 5.43 8.26 (1H, dd, J ¼ 8.0 Hz, J ¼ 1.0 Hz), 7.99–7.95 (1H, m), 7.82 (1H,
(1H, d, J ¼ 16.4 Hz), 4.94 (1H, d, J ¼ 16.8 Hz), 2.11 (3H, s); 13C d, J ¼ 8.0 Hz), 7.68 (1H, t, J ¼ 8.0 Hz), 7.55 (1H, d, J ¼ 1.5 Hz),
NMR (100 MHz, DMSO-d6) d 160.5, 154.4, 153.3, 137.8, 135.2, 7.49 (1H, d, J ¼ 9.0 Hz), 7.43 (1H, dd, J ¼ 8.5 Hz, J ¼ 2.0 Hz); 13
C
129.0, 128.8, 127.8, 126.9, 126.6, 123.6, 120.1, 119.9, 116.3, 110.8, NMR (100 MHz, DMSO-d6) d 160.1, 147.8, 147.5, 136.1, 134.5,
107.7, 46.6, 8.1; HRMS (ESI-MS) calcd for C20H17N3O (M + H) 134.1, 131.1, 128.7, 128.2, 127.1, 126.9, 123.2, 121.7, 115.0,
316.1450, found 316.1451.
113.6, 58.1; HRMS (ESI-MS) calcd for C16H9Br79IN3O (M + H)
3-(1H-indol-2-yl)-3H-quinazolin-4-one (5a). Compound was 465.9052, found 465.9049, C16H9Br81IN3O (M + H) 467.9031,
obtained as yellow solid (89 mg, 50%); m.p. ¼ 140 ꢁC; IR (KBr) found 467.9028.
3276, 2920, 1660, 1600, 1265, 1008, 734 cmꢀ1
;
1H NMR (400
3-(6-Bromo-1H-indol-2-yl)-3H-quinazolin-4-one (5d)
MHz, DMSO-d6) d 11.81 (1H, s), 8.49 (1H, s), 8.23 (1H, d, J ¼ 8.0
3-(6-Bromo-3-iodo-1H-indol-2-yl)-3H-quinazolin-4-one
Hz), 7.92–7.88 (1H, m), 7.77 (1H, d, J ¼ 8.0 Hz), 7.63 (2H, t, J ¼ Compounds were obtained as bright yellow solid mixture with
(5dd).
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ratio of (5d : 5dd ¼ 0.3 : 1); (overall 160 mg, 54%); IR (KBr) 3342, Hz), 7.22–7.21 (3H, m), 7.00–6.96 (2H, m), 6.82 (1H, s), 6.30–6.28
2915, 1676, 1610, 1413, 1260, 772, 701 cmꢀ1; 1H NMR (400 MHz, (1H, m), 6.25–6.24 (1H, m), 5.00–4.92 (2H, m); 13C NMR (100
DMSO-d6) d 12.48 (1H, s), 11.96 (0.304H, s), 8.49 (0.326H, s), 8.41 MHz, CDCl3) d 161.4, 147.7, 147.1, 136.8, 134.8, 128.8, 128.0,
(0.994H, s), 8.26–8.24 (1.35H, m), 7.98–7.90 (1.48H, m), 7.82– 127.7, 127.6, 127.2, 127.0, 125.2, 122.0, 121.9, 107.7, 107.1, 50.9;
7.76 (1.356H, m), 7.72 (1.048H, s), 7.68–7.62 (1.672H, m), 7.59– HRMS (ESI-MS) calcd for C19H15N3O (M + H) 302.1293, found
7.57 (0.334H, m), 7.35 (2.14H, s), 7.22–7.20 (0.346H, m), 6.73 302.1293.
(0.298H, s); 13C NMR (100 MHz, DMSO-d6) d 160.1, 147.9, 147.5,
3-(1-Methyl-1H-pyrrol-2-yl)-3H-benzo[g]quinazolin-4-one (7d).
147.2, 136.0, 135.9, 135.7, 134.0, 128.6, 128.4, 128.2, 127.9, Compound was obtained as yellow solid (65 mg, 35%); m.p. ¼
127.0, 125.9, 124.2, 123.0, 121.8, 116.8, 115.3, 114.6, 98.2, 59.1; 152 ꢁC; IR (KBr) 2958, 2926, 1682, 1605, 1265, 756 cmꢀ1; 1H NMR
HRMS (ESI-MS) calcd for 5d C16H10Br79N3O (M + H) 340.0085, (400 MHz, CDCl3) d 8.98 (1H, s), 8.26 (1H, s), 8.10–8.02 (3H, m),
found 340.0075; C16H10Br81N3O (M + H) 342.0065, found 7.67 (1H, t, J ¼ 6.8 Hz), 7.60 (1H, t, J ¼ 7.2 Hz), 6.76–6.75 (1H, m),
342.0056, for 5dd C16H9Br79IN3O (M + H) 465.9052, found 6.26–6.24 (2H, m), 3.53 (3H, s); 13C NMR (100 MHz, CDCl3) d
465.9049; C16H9Br81IN3O (M + H) 467.9031, found 467.9029.
161.8, 146.2, 143.0, 136.7, 131.9, 129.5, 129.1, 128.9, 128.2, 126.9,
3-(1-Methyl-1H-indol-2-yl)-3H-quinazolin-4-one
(5e). 125.8, 125.5, 122.0, 120.4, 107.4, 106.2, 33.4; HRMS (ESI-MS)
Compound was obtained as red solid (84 mg, 45%); m.p. ¼ 178 calcd for C17H13N3O (M + H) 276.1137, found 276.1138.
1
ꢁC; IR (KBr) 3106, 2920, 1676, 1600, 1238, 810, 772 cmꢀ1; H
3-Methyl-1,3-dihydro-indol-2-one (8).21 This compound was
NMR (400 MHz, DMSO-d6) d 8.37 (1H, s), 8.24 (1H, d, J ¼ 7.6 Hz), veried by the literature values.
7.93 (1H, t, J ¼ 8.0 Hz), 7.79 (1H, d, J ¼ 8.0 Hz), 7.66–7.63 (2H,
3,30-Dimethyl-30H-[1,20] biindolyl-30-ol (9).22 Compound was
m), 7.54 (1H, d, J ¼ 8.4 Hz), 7.28 (1H, t, J ¼ 7.6 Hz), 7.14 (1H, t, J obtained as yellow solid (31 mg, 22%); m.p. ¼ 174 ꢁC; IR (KBr)
¼ 7.6 Hz), 6.72 (1H, s), 3.56 (3H, s); 13C NMR (100 MHz, DMSO- 3347, 3052, 1791, 1561, 1205, 942, 745 cmꢀ1; 1H NMR (400 MHz,
d6) d 160.9, 148.1, 147.9, 135.9, 135.7, 133.0, 128.4, 128.0, 127.1, DMSO-d6) d 8.78 (1H, d, J ¼ 8.0 Hz), 8.06 (1H, s), 7.60 (1H, d, J ¼
126.1, 122.9, 121.9, 121.3, 120.4, 110.7, 99.6, 29.8; HRMS (ESI- 7.6 Hz), 7.44–7.28 (5H, m), 7.16 (1H, t, J ¼ 7.6 Hz), 6.68 (1H, s),
MS) calcd for C17H13N3O (M + Na) 298.0956, found 298.0960.
2.31 (3H, s), 1.65 (3H, s); 13C NMR (100 MHz, DMSO-d6) d 170.9,
3-(1-Butyl-1H-indol-2-yl)-3H-quinazolin-4-one
(5f). 151.9, 140.9, 135.9, 130.90, 129.7, 124.9, 124.6, 123.2, 122.1,
Compound was obtained as red solid; (112 mg, 52%); m.p. ¼ 119.3, 117.1, 116.6, 81.9, 26.3, 9.9; HRMS (ESI-MS) calcd for
170 ꢁC; IR (KBr) 3025, 2920, 1670, 1600, 1310, 926, 701 cmꢀ1; 1H
C
18H16N2O (M + H) 277.1341, found 277.1344.
NMR (400 MHz, DMSO-d6) d 8.42 (1H, s), 8.24 (1H, d, J ¼ 7.6 Hz),
1-(1,3-Dimethyl-1H-indol-2-yl)-pyrrolidine-2,5-dione
(10).
7.96–7.92 (1H, m), 7.80 (1H, d, J ¼ 8.0 Hz), 7.67–7.63 (2H, m), Compound was obtained as yellow solid; m.p. ¼ 178 ꢁC; IR (KBr)
7.56 (1H, d, J ¼ 8.0 Hz), 7.27 (1H, t, J ¼ 7.2 Hz), 7.13 (1H, t, J ¼ 2926, 2367, 1720, 1479, 1167, 750 cmꢀ1
;
1H NMR (400 MHz,
7.6 Hz), 6.71 (1H, s), 4.06 (1H, s), 3.86 (1H, s), 1.57 (2H, s), 1.13 DMSO-d6) d 7.54 (1H, d, J ¼ 8.0 Hz), 7.41 (1H, d, J ¼ 8.0 Hz), 7.22
(2H, s), 0.71 (3H, t, J ¼ 7.6 Hz); 13C NMR (100 MHz, DMSO-d6) d (1H, t, J ¼ 7.2 Hz), 7.08 (1H, t, J ¼ 7.2 Hz), 3.48 (3H, s), 2.94 (4H,
160.9, 147.9, 135.8, 135.3, 132.4, 128.5, 128.1, 127.1, 126.3, s), 2.05 (3H, s); 13C NMR (100 MHz, DMSO-d6) d 177.4, 135.4,
123.0, 121.9, 121.4, 120.4, 110.9, 100.2, 42.8, 31.9, 19.8, 13.9; 126.6, 124.5, 122.7, 119.5, 119.3, 110.2, 107.2, 29.5, 29.2, 8.4;
HRMS (ESI-MS) calcd for C20H19N3O (M + H) 318.1606, found HRMS (ESI-MS) calcd for C14H14N2O2 (M + H) 243.1134, found
318.1606.
3-(1H-Pyrrol-2-yl)-3H-quinazolin-4-one (7a). Compound was
243.1133.
3-[1-(3-Bromo-propyl)-3-methyl-1H-indol-2-yl]-3H-quinazolin-
obtained as yellow semisolid (74 mg, 52%); IR (KBr) 3043, 2934, 4-one (15). In the reaction mixture of 3-(3-methyl-1H-indol-2-yl)-
1675, 1420, 863 cmꢀ1; 1H NMR (400 MHz, CDCl3) d 10.01 (1H, s), 4a and 8a-dihydro-3H-quinazolin-4-one (3a) (0.100 g, 0.36 mmol)
8.34 (1H, s), 8.29 (1H, d, J ¼ 8.0 Hz), 7.80–7.72 (2H, m), 7.54–7.50 in dry DMF solvent (5 ml), K2CO3 (0.100 g, 0.72 mmol) was added
(1H, m), 6.84–6.82 (1H, m), 6.29–6.27 (1H, m), 6.26–6.25 (1H, and stirred at RT for 1 h. Then, 1,3-dibromopropane (0.109 g,
m); 13C NMR (100 MHz, CDCl3) d 160.8, 147.0, 144.6, 134.7, 0.54 mmol) was added to the reaction mixture dropwise and
127.9, 127.7, 126.9, 126.4, 121.8, 116.8, 108.1, 100.4; HRMS (ESI- stirred at RT for another 5 h. Then, the reaction mixture was
MS) calcd for C12H9N3O (M + H) 212.0824, found 212.0830.
extracted with EtOAc, dried over Na2SO4 and evaporated in
3-(1-Methyl-1H-pyrrol-2-yl)-3H-quinazolin-4-one
(7b). vacuum. The residue was puried by column chromatography
Compound was obtained as yellow solid (88 mg, 58%); m.p. ¼ on silica gel (EtOAc : hexane ¼ 1 : 9) to afford the desired
112 ꢁC; IR (KBr) 3117, 3073, 1687, 1600, 1320, 772 cmꢀ1 1H product (15) (78 mg; 55% yield). This compound was obtained as
;
NMR (400 MHz, CDCl3) d 8.38 (1H, d, J ¼ 7.6 Hz), 8.10 (1H, s), yellow sticky semisolid with little inseparable impurities; IR
7.84–7.78 (2H, m), 7.58 (1H, t, J ¼ 7.6 Hz), 6.74 (1H, s), 6.232– (KBr) 3052, 2920, 1693, 1610, 1276, 920 cmꢀ1
;
1H NMR (500
6.226 (2H, m), 3.50 (3H, s); 13C NMR (100 MHz, CDCl3) d 161.2, MHz, CDCl3) d 8.42 (1H, d, J ¼ 7.5 Hz), 8.025 (1H, s), 7.89–7.84
147.7, 147.2, 134.9, 127.9, 127.6, 127.3, 125.3, 122.2, 121.9, (2H, m), 7.67 (1H, d, J ¼ 8.0 Hz), 7.63 (1H, t, J ¼ 7.5 Hz), 7.46 (1H,
107.4, 106.3, 33.5; HRMS (ESI-MS) calcd for C13H11N3O (M + H) d, J ¼ 8.0 Hz), 7.38–7.35 (1H, m), 7.24 (1H, t, J ¼ 7.5 Hz), 4.24–
226.0980, found 226.0979.
4.10 (2H, m), 3.39–3.29 (2H, m), 2.33–2.23 (2H, m), 2.24 (3H, s);
3-(1-Benzyl-1H-pyrrol-2-yl)-3H-quinazolin-4-one
(7c). 13C NMR (125 MHz, CDCl3) d 161.1, 147.9, 146.6, 135.1, 133.2,
Compound was obtained as yellow solid (102 mg, 50%); m.p. ¼ 128.1, 127.9, 127.4, 126.9, 123.5, 122.2, 120.0, 119.8, 117.0, 109.8,
178 ꢁC; IR (KBr) 3603, 2920, 1693, 1610, 1276, 723 cmꢀ1 1H 108.5, 41.4, 32.4, 30.5, 8.1; HRMS (ESI-MS) calcd for
;
NMR (400 MHz, CDCl3) d 8.36 (1H, d, J ¼ 8.0 Hz), 7.79 (1H, t, J ¼ C20H18Br79N3O (M
+
H) 396.0711, found 396.0711;
7.2 Hz), 7.69 (1H, d, J ¼ 8.0 Hz), 7.65 (1H, s), 7.56 (1H, t, J ¼ 8.0 C20H18Br81N3O (M + H) 398.0691, found 398.0693.
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14-methyl-7,8-dihydroindolo[20,10:2,3][1,3]diazepino[7,1-b]
RSC Advances
R. Hatley and M. J. Gaunt, J. Am. Chem. Soc., 2006, 128,
2528–2529.
quinazolin-16(6H)-one (16). To a freshly prepared solution ꢁof
LDA (0.054 g, 0.50 mmol) in anhydrous THF (8 ml) at ꢀ78 C
under nitrogen atmosphere, a solution of 3-[1-(3-bromo-propyl)-
3-methyl-1H-indol-2-yl]-3H-quinazolin-4-one (15) (0.100 g, 0.25
mmol) in THF and HMPA (0.180 g, 1.00 mmol) was added
dropwise. The reaction mixture was stirred for another 3 h at
ꢀ78 ꢁC, followed by additional 2 h at RT. Then, the reaction
mixture was quenched with saturated solution of NH4Cl and
extracted with EtOAc. The solvent was dried over Na2SO4 and
evaporated in vacuum. The residue was puried by column
chromatography on silica gel (EtOAc : hexane ¼ 3 : 7) to afford
the desired product 16 (55 mg, 42% yield). This compound was
obtained as yellow solid; m.p. ¼ 158 ꢁC; IR (KBr) 3046, 2958,
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2920, 1693, 1605, 1457, 1260, 739 cmꢀ1 1H NMR (400 MHz,
;
CDCl3 + DMSO-d6) d 8.22 (1H, d, J ¼ 8.0 Hz), 7.89 (1H, t, J ¼ 7.2
Hz), 7.72 (1H, d, J ¼ 8.0 Hz), 7.63–7.56 (3H, m), 7.23 (1H, t, J ¼
7.6 Hz), 7.11 (1H, t, J ¼ 7.2 Hz), 4.62–4.57 (1H, m), 4.02–3.95 (1H,
m), 2.78–2.74 (1H, m), 2.25–2.17 (3H, m), 2.11 (3H, s); 13C NMR
(100 MHz, CDCl3 + DMSO-d6) d 159.6, 156.1, 147.4, 135.4, 133.5,
127.9, 127.6, 127.6, 127.3, 127.0, 122.7, 121.0, 119.8, 119.4,
110.0, 106.2, 39.0, 32.9, 27.6, 9.4; HRMS (ESI-MS) calcd for
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C
20H17N3O (M + H) 316.1450, found 316.1448.
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5229.
Acknowledgements
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Commun., 2012, 48, 2343–2345.
We are grateful to DST for nancial support (project number:
SR/S1/OC-70/2008) and for the single-crystal X-ray diffractom-
eter facility in our school. S.K.G also thanks UGC for the Junior
Research Fellowship.
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Paper
ꢀ
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¼ 106.686(4)ꢁ, g ¼ 110.923(4)ꢁ and space group P1.
Molecular formula: C18H15N3O1, unit cell parameters: a ¼
˚
8.3989(18), b ¼ 12.9656(14), c ¼ 13.6993(18) A, b ¼
101.702(16)ꢁ and space group P21/n. Molecular formula:
C
16H10I1N3O1, unit cell parameters: a ¼ 13.0741(18), b ¼
ꢁ
˚
4.2988(4), c ¼ 24.974(3) A, b ¼ 100.040(11) and space
21 R. G. Alvarez, I. S. Hunter, C. J. Suckling, M. Thomas and
U. Vitinius, Tetrahedron, 2001, 57, 8581–8587.
group P21/n. Molecular formula: C18H16N2O1, unit cell
parameters:
a
a
¼
¼
10.8278(7),
b
b
¼
¼
11.3669(8),
106.227(5)ꢁ,
c
g
¼
¼
100.716(5)ꢁ,
˚
22 Molecular formula: C17H13N3O1, unit cell parameters: a ¼
13.0687(6)A,
ꢁ
ꢁ
˚
ꢀ
10.830(3), b ¼ 12.205(3), c ¼ 12.209(3) A, a ¼ 102.677(4) , b
104.477(6) and space group P1.†
20144 | RSC Adv., 2014, 4, 20136–20144
This journal is © The Royal Society of Chemistry 2014