SnCl2-catalyzed selective atom economic imino Diels-Alder reaction: Synthesis of 2-(1 H-pyrrolo[2,3-b ]pyridin-3-yl)quinolines

Article abstract of DOI:10.1021/jo202256z

The synthesis of 2-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinolines by a SnCl ₂-catalyzed multicomponent reaction has been described. The reaction proceeds chemo- and regioselectively in an atom-economic way, generating a library of 24 quinoline derivatives.

Full text of DOI:10.1021/jo202256z

Article
pubs.acs.org/joc
SnCl2-Catalyzed Selective Atom Economic Imino Diels−Alder
Reaction: Synthesis of 2-(1H-Pyrrolo[2,3-b]pyridin-3-yl)quinolines
Rajendran Suresh,†,‡ Shanmugam Muthusubramanian,*,† Rajendran Senthilkumaran,‡
and Govindaswamy Manickam‡
†Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai, 625 021, India
‡Syngene International Limited, Biocon, Bangalore, 560 099, India
S
* Supporting Information
ABSTRACT: The synthesis of 2-(1H-pyrrolo[2,3-b]pyridin-
3-yl)quinolines by a SnCl2-catalyzed multicomponent reaction
has been described. The reaction proceeds chemo- and regio-
selectively in an atom-economic way, generating a library of
24 quinoline derivatives.
INTRODUCTION
RESULTS AND DISCUSSION
■
■
Heterocyclic compounds embedded with nitrogen are prevalent
in nature and present in numerous natural products and pharm-
aceutical leads. Among the nitrogen heterocycles, quinoline
derivatives are important motifs, widely found in many natural
products, many of them displaying biological activities such as
antimalarial, antimicrobial, antifungal, antineoplastic, anti-HIV,
antituberclosis, anticancer, and antibacterial properties.1−3
Owing to their biological importance, these derivatives attract
the attention of synthetic chemists, and hence, many synthetic
strategies are dedicated to access these frameworks. Skraup
We have planned to link two biologically important nuclei,
quinolines and azaindoles, to generate a new set of compounds,
(1H-pyrrolo[2,3-b]pyridin-3-yl)quinoline analogues, using
Povarov reaction by the cycloaddition of aldimine containing
7-azaindole unit and alkyne. It must be mentioned that usage of
alkyne as a component for Povarov reaction is not as popular as
with alkene.13 The general synthetic strategy of the present
investigation is shown in Scheme 1. Following the literature
procedure, 7-azaindole-3-carboxaldehyde 1 was obtained from
7-azaindole in two steps.15 Treatment of 1 with substituted
aniline 2 under acidic condition would have formed the
intermediate N-aryl aldimine 3, which subsequently undergoes
[4 + 2]-cycloaddition with substituted alkyne 4 followed by
aerobic dehydrogenation to afford directly quinoline derivatives 5.
In order to select the suitable acid to promote this one-pot
Povarov reaction, the reaction has been screened with azaindole
1, 4-methoxyaniline (2b), and phenylacetylene (4a), taken with
different Lewis acids in stoichiometric ratio. The choice between
toluene, ethanol, and acetonitrile as a solvent has also been
optimized. The details are presented in Table 1. It can be seen
that the reaction leads to a mixture of products having quino-
line 5b and the deprotected (1H-pyrrolo[2,3-b]pyridin-3-yl)-
quinoline derivative 6b. Though boron triflouride diethyl etherate
has been widely used for Povarov reactions, it is noticed that
stannous chloride is competent enough as the acid source. When
only 20 mol % of stannous chloride in acetonitrile was used, very
good yield of 5b, with negligible amount of 6b, has been achieved.
It is noteworthy that (i) titanium(IV) chloride in acetonitrile gives
exclusively 6b with no trace of 5b, (ii) when titanium(IV) iso-
propoxide is employed, the reaction does not go at all,
(iii) camphorsulfonic acid is not effective in this conversion,
reaction,4a,b Combes synthesis,4c Friedlander synthesis4d and
̈
Doebner−Miller reaction4e are a few well-recognized synthetic
protocols employed for the preparation of quinoline deriva-
tives.5 Recently, the imino Diels−Alder reaction, known as
Povarov reaction, has become one of the most important
protocols for the synthesis of tetrahydroquinoline derivatives.6
Interestingly, Povarov reaction can be promoted either by
Lewis acid7a−e or protic acid7f−h or by even iodine7i through
cycloaddition of N-aryl aldimine, generated in situ from aniline
and aldehyde, with alkene yielding the tetrahydroquinoline deri-
vatives.8 To get quinoline from tetrahydro/dihydroquinoline,
the latter should be subjected to oxidation under harsh con-
ditions9 or dehydrogenation by hydrogen transfer process10 or
acid-catalyzed elimination reactions.11 On the other hand, one
can utilize acetylene derivative as dienophile to form dihydro-
quinoline, which in situ undergoes aerobic oxidation12 to the
corresponding quinoline.13
Azaindole is yet another nucleus known to be part of many
biologically active compounds, occupying a unique position in
medicinal and pharmaceutical chemistry and serving as a
building block in synthetic chemistry.14
Received: November 17, 2011
Published: January 9, 2012
© 2012 American Chemical Society
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Scheme 1. Synthesis of 4-Substituted-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)quinoline
Table 1. Screening Impact of Solvents and Lewis Acids
a
b
b
entry
Lewis acid (100 mol %)
Solvent at reflux temp
yield of 5b (%)
yield of 6b (%)
1
BF3·OEt2
BF3·OEt2
BF3·OEt2
CSA
EtOH
4
18
42
4
62
36
34
2
toluene
CH3CN
CH3CN
CH3CN
toluene
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
3
4
5
InCl3
31
9
29
33
39
54
67
42
46
76
6
p-TsOH
Sc(OTf)3
FeCl3
7
40
19
13
8
9
10
11
12
13
14
15
16
17
La(OTf)3
ZnCl2
InBr3
29
TiCl4
Ti(OPr)4
AgOTf
SnCl2
28
47
86
45
42
5
c
SnCl2
a
b
c
Reaction time:12 h. Isolated yield. 20 mol % catalyst used.
and (iv) acetonitrile is found to be superior as solvent over
ethanol or toluene. The reaction has been carried out under the
optimized conditions (20 mol % of SnCl2, acetonitrile, 80 °C)
for various combinations of aryl amines and acetylene deriva-
tives to get different 5. Under this condition, 6 was obtained
The substituent of the alkyne occupies the fourth position of
the quinoline and not the third position. It is the double bond
of the N-aryl ring, not that of the 7-azaindole, that plays part of
the diene in this imino Diels−Alder reaction, exhibiting another
selectivity. Another selectivity has been noticed during the
formation of 5d, 5m, and 5o, where it is the triple bond, not the
double bond, of 1-ethynyl cyclohexene that has participated in
the cycloaddition. In addition, the reaction works well, whether
electron-donating or -withdrawing groups are present in the
o- or p-position of the aniline ring.
When m-substituted anilines were used as the amine com-
ponent, both 5- and 7-substituted regioisomers were obtained
in almost equal amounts and have been successfully separated.
It is easy to distinguish between these two isomers from their
NMR data. These two regioisomers could not be isolated in the
case of 5w and 5w′, though the crude NMR spectrum suggests
a nearly 1:1 ratio of these isomers.
only in traces.
The amines employed were ortho-, para-, or meta-substituted
anilines, naphthylamines, and some heterocyclic amines, while a
variety of aryl/heteroaryl and cyclohexenyl acetylenes have
been used as the dienophiles, yielding a range of products with
good yield (Table 2). 2-Aminopyridine, 4-aminopyridine, and
2-aminopyrazine have not undergone this reaction, no matter
which acetylenic component was employed. The reduced
nucleophilicity of the amino group could be the reason for this,
as the imine formation itself would have been difficult in these
cases.
Products have been adequately characterized by 1H, 13C, and
mass spectral data. The reaction proceeds regioselectively,
and the regiochemistry of the product formed has been
unambiguously assigned by the single crystal X-ray analysis
of 5b (see the Supporting Information for more details).
The suitability of this protocol to this class of compounds has
been tested with another reaction. 7-Azaindole-2-caroxaldehyde 7,
which was prepared from 7-azaindole by a literature method,16
underwent smooth Povarov reaction with 2b and 4a (Scheme 2).
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However, only the deprotected quinoline derivatives 8 were
obtained, in this case in 76% yield. It is not understood why the
cycloadduct originating from azaindole 2-aldehyde 7 undergoes total
deprotection giving 8, while that is not the case with 5. The possible
hydrogen bonding of N−H with the quinoline nitrogen may be a
stabilizing factor in 8.
Table 2. Synthesis of 4-Substituted-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)quinoline 5
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Table 2. continued
a
The mixture of regioisomers could not be separated.
It must be mentioned that the reaction proceeded even with
the unprotected 7-azaindole 9a, but the yield was relatively
poor. When unprotected 7-azaindole-3-carboxaldehyde 9a
reacted with differently substituted acetylenes and anilines, a
few derivatives of 6 (6b, 6c, 6d, 6j, and 6n) have been prepared
and characterized (Table 3). In order to check the role of the
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Scheme 2. Synthesis of 6-Methoxy-4-phenyl-2-(1H-pyrrolo[2,3-b]pyridin-2-yl)quinoline
Table 3. Synthesis of 4-Substituted-2-(1-(substituted)-1H-pyrrolo[2,3-b]pyridin-3-yl)quinoline 5
protecting group in this aza Diels−Alder reaction, the reaction
has been carried out with N-methyl-17 and N-benzyl-derived18
azaindoles (9b and 9c). The reaction went on smoothly in
these cases too, with appreciable yields of 10 and 11, respectively
(Table 3).
the first time. The reaction has been found to be chemo- and
regioselective with good atom efficiency.
EXPERIMENTAL SECTION
■
General Remarks. Nuclear magnetic resonance (1H and 13C
NMR) spectra were recorded on a 400 MHz spectrometer in CDCl3
using TMS as internal standard. Chemical shifts are reported in parts
per million (δ), coupling constants (J-values) are reported in hertz
(Hz), and spin multiplicities are indicated by the following symbols: s
(singlet), d (doublet), t (triplet), q (quartet), m (multiplet), bs (broad
singlet). 13C NMR spectra were routinely run with broadband
decoupling.
CONCLUSION
■
In summary, a facile and efficient method is described for the
one-pot synthesis of a range of quinoline derivatives linked
to azaindole by a Povarov reaction in good yields. SnCl2, a
cheap Lewis acid, has been used to promote the reaction for
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General Procedure for the Synthesis of 4-Substituted-
2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)quinoline.
The mixture of 7-azaindole-3-carboxaldehyde 1 (1.0 mmol), amine 2
(1.05 mmol) in acetonitrile, and stannous chloride (0.2 mmol) was
stirred at room temperature for 10 min, and then alkyne 4 (1.5 mmol)
was added to the above mixture. The stirring was then continued at
80 °C for 12 h. The reaction mixture was then quenched with
ammonium chloride solution and extracted with ethyl acetate. The
organic layer was washed with water and brine, dried over sodium
sulfate, and concentrated in vacuum. Crude product was purified by
column chromatography using ethyl acetate−hexane as the solvent to
get quinoline derivative 5.
4-Phenyl-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-
3-yl)quinoline (5a). Isolated as orange solid: mp 236−239 °C;
1H NMR (400 MHz, CDCl3) δ 7.37 (dd, J = 8.0, 4.8 Hz, 1H, Ar−H),
7.48 (t, J = 8.0 Hz, 2H, Ar−H), 7.48 (s, 1H, Ar−H), 7.53−7.61
(m, 6H, Ar−H), 7.77 (t, J = 7.6 Hz, 1H, Ar−H), 7.77 (s, 1H, Ar−H),
7.92 (d, J = 7.6 Hz, 1H, Ar−H), 8.21 (d, J = 7.2 Hz, 1H, Ar−H), 8.26
(d, J = 7.6 Hz, 2H, Ar−H), 8.37 (bs, 1H, Ar−H), 8.53 (dd, J = 4.8,
1.6 Hz, 1H, Ar−H), 9.15 (d, J = 7.2, Hz, 1H, Ar−H); 13C NMR
(100 MHz, CDCl3) δ 118.9, 119.8, 121.6, 121.9, 125.5, 125.6, 125.8,
126.4, 127.2, 128.1, 128.6, 128.7, 128.9, 129.0, 129.3, 129.5, 129.7,
132.4, 134.2, 137.9, 138.0, 145.6, 147.9, 152.1; UPLC (M + 1) 462.3.
Anal. Calcd for C28H19N3O2S: C, 72.87; H, 4.15; N, 9.10. Found: C,
72.80; H, 4.19; N, 9.18.
6-Methoxy-4-phenyl-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]-
pyridin-3-yl)quinoline (5b). Isolated as pale yellow solid: mp 222−
224 °C; 1H NMR (400 MHz, CDCl3) δ 3.81 (s, 3H, −OMe), 7.20 (d,
J = 2.8 Hz, 1H, Ar−H), 7.35 (dd, J = 8.0, 4.8 Hz, 1H, Ar−H), 7.40
(dd, J = 9.2, 2.8 Hz, 1H, Ar−H), 7.48 (t, J = 8.0 Hz, 2H, Ar−H),
7.50−7.60 (m, 6H, Ar−H), 7.69 (s, 1H, Ar−H), 8.11 (d, J = 8.8 Hz,
1H, Ar−H), 8.24 (d, J = 8.0 Hz, 2H, Ar−H), 8.30 (s, 1H, Ar−H), 8.52
(d, J = 4.4 Hz, 1H, Ar−H), 9.10 (d, J = 8.0 Hz, 1H, Ar−H); 13C NMR
(100 MHz, CDCl3) δ 55.2, 103.7, 118.69, 119.7, 120.1, 120.9, 121.5,
125.7, 126.9, 127.6, 128.6, 128.7, 129.5, 129.6, 131.1, 132.6, 134.9,
137.4, 137.5, 143.8, 145.3, 146.8, 147.2, 149.9, 157.4; UPLC (M + 1)
492.4. Anal. Calcd for C29H21N3O3S: C, 70.86; H, 4.31; N, 8.55.
Found: C, 70.73; H, 4.26; N, 8.62.
6-Methoxy-4-(2-methoxyphenyl)-2-(1-(phenylsulfonyl)-1H-
pyrrolo[2,3-b]pyridin-3-yl)quinoline (5c). Isolated as orange solid:
mp 211−213 °C; 1H NMR (400 MHz, CDCl3) δ 3.77 (s, 3H,
−OMe), 3.78 (s, 3H, −OMe), 6.88 (d, J = 2.8 Hz, 1H, Ar−H), 7.12
(d, J = 8.4 Hz, 1H, Ar−H), 7.16 (t, J = 7.6 Hz, 1H, Ar−H), 7.32−7.38
(m, 3H, Ar−H), 7.46−7.57 (m, 4H, Ar−H), 7.70 (s, 1H, Ar−H), 8.08
(d, J = 9.2 Hz, 1H, Ar−H), 8.22 (dd, J = 7.2, 1.6 Hz, 2H, Ar−H), 8.27
(s, 1H, Ar−H), 8.51 (dd, J = 4.8, 1.6 Hz, 1H, Ar−H), 9.08 (dd, J =
8.0, 1.6.Hz, 1H, Ar−H); 13C NMR (100 MHz, CDCl3) δ 55.4, 55.5,
104.4, 111.2, 119.6, 120.0, 120.2, 120.9, 121.6, 121.7, 124.7, 126.8,
127.2, 128.0, 129.0, 130.1, 131.0, 131.2, 132.3, 134.1, 138.2, 144.4,
145.1, 145.5, 147.9, 149.7, 156.7, 157.6; UPLC (M + 1) 522.4. Anal.
Calcd for C30H23N3O4S: C, 69.08; H, 4.44; N, 8.06. Found: C, 69.01;
H, 4.48; N, 8.02.
4.8 Hz, 1H, Ar−H), 7.61−7.64 (m, 4H, Ar−H), 7.72 (t, J = 7.6 Hz,
1H, Ar−H), 8.08 (d, J = 8.8 Hz, 1H, Ar−H), 8.18 (d, J = 8.0 Hz, 2H,
Ar−H), 8.20 (s, 1H, Ar−H), 8.46 (d, J = 4.8 Hz, 1H, Ar−H), 9.03
(s, 1H, Ar−H), 9.25 (dd, J = 8.0, 0.8 Hz, 1H, Ar−H), 9.73 (s, 1H,
−OH); 13C NMR (100 MHz, DMSO-d6) δ 21.4, 115.4, 116.4, 118.6,
119.1, 120.1, 120.3, 120.9, 124.1, 124.8, 127.3, 127.6, 129.3, 129.6,
129.7, 131.7, 132.6, 134.8, 136.0, 137.4, 138.7, 145.3, 146.4, 147.2,
147.7, 151.4, 157.5; UPLC (M + 1) 492.3. Anal. Calcd for
C29H21N3O3S: C, 70.86; H, 4.31; N, 8.55. Found: C, 70.75; H, 4.27;
N, 8.62.
4-(4-Ethylphenyl)-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]-
pyridin-3-yl)-6-(trifluoromethyl)quinoline (5f). Isolated as orange
1
solid: mp 212−214; °C H NMR (400 MHz, CDCl3) δ 1.38 (t, J =
7.6 Hz, 3H, −CH3), 2.83 (q, J = 7.6 Hz, 2H, −CH2), 7.38 (dd, J =
8.0, 4.8 Hz, 1H, Ar−H), 7.44−7.53 (m, 6H, Ar−H), 7.60 (t, J =
7.6 Hz, 1H, Ar−H), 7.83 (s, 1H, Ar−H), 7.91 (d, J = 8.8 Hz, 1H,
Ar−H), 8.26−8.32 (m, 4H, Ar−H), 8.43 (s, 1H, Ar−H), 8.54 (d, J =
8.4 Hz, 1H, Ar−H), 9.13 (d, J = 8.0 Hz, 1H, Ar−H); 13C NMR (100
MHz, CDCl3) δ 15.5, 28.7, 119.9, 120.9, 121.3, 123.8, 123.9, 124.8,
125.4, 125.5, 126.2, 127.8, 128.1, 128.2, 128.5, 129.1, 129.4, 130.7,
132.4, 134.2, 134.3, 137.9, 145.5, 145.8, 147.8, 149.9, 154.2; UPLC
(M + 1) 558.3. Anal. Calcd for C31H22F3N3O2S: C, 66.78; H, 3.98; N,
7.54. Found: C, 66.81; H, 4.02; N, 7.59.
4-(Biphenyl-4-yl)-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]-
pyridin-3-yl)-6-(trifluoromethyl)quinoline (5g). Isolated as pale
yellow solid: mp 195−197 °C; 1H NMR (400 MHz, CDCl3) δ 7.39−
7.56 (m, 6H, Ar−H), 7.61 (t, J = 7.6 Hz, 1H, Ar−H), 7.68 (d, J =
8.0 Hz, 2H, Ar−H), 7.75 (d, J = 9.2 Hz, 2H, Ar−H), 7.87 (dd, J = 6.4,
1.6 Hz, 2H, Ar−H),7.89 (s, 1H, Ar−H), 7.93 (dd, J = 8.8, 2.0 Hz, 1H,
Ar−H), 8.27−8.30 (m, 2H, Ar−H), 8.33 (d, J = 8.8 Hz, 1H, Ar−H),
8.46 (s, 1H, Ar−H), 8.55 (dd, J = 4.8, 1.6 Hz, 2H, Ar−H), 9.16
(dd, J = 8.0, 1.6 Hz, 1H, Ar−H); 13C NMR (100 MHz, CDCl3)
δ 118.9, 119.8, 119.9, 121.4, 122.6, 123.7, 123.8, 124.7, 125.4, 126.2,
127.2, 127.7, 127.9, 128.2, 129.0, 129.1, 129.9, 130.8, 132.4, 134.3,
135.8, 137.9, 140.2, 142.1, 145.8, 147.8, 149.6, 149.8, 154.2; UPLC
(M + 1) 606.3. Anal. Calcd for C35H22F3N3O2S: C, 69.41; H, 3.66; N,
6.94. Found: C, 69.37; H, 3.69; N, 6.87.
6-Nitro-4-phenyl-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]-
pyridin-3-yl)quinoline (5h). Isolated as orange solid: mp 228−
230 °C; 1H NMR (400 MHz, CDCl3) δ 7.40 (dd, J = 8.0, 4,8 Hz, 1H, Ar−
H), 7.52 (t, J = 8.0 Hz, 2H, Ar−H), 7.58−7.67 (m, 6H, Ar−H), 7.89
(s, 1H, Ar−H), 8.27−8.31 (m, 3H, Ar−H), 8.48 (s, 1H, Ar−H), 8.49
(dd, J = 7.6, 2.4 Hz, 1H, Ar−H), 8.55 (dd, J = 8.4, 0.8 Hz, 1H, Ar−H),
8.84 (d, J = 2.4 Hz, 1H, Ar−H), 9.15 (dd, J = 8.4, 0.8 Hz, 1H, Ar−H);
13C NMR (100 MHz, CDCl3) δ 118.6, 120.0, 120.3, 121.2, 122.9,
123.3, 124.6, 126.9, 128.3, 129.2, 129.3, 129.4, 129.6, 131.2, 132.4,
134.5, 136.5, 137.8, 145.4, 146.0, 147.8, 150.9, 151.0, 155.5; UPLC
(M + 1) 507.4. Anal. Calcd for C28H18N4O4S: C, 66.39; H, 3.58; N,
11.06. Found: C, 66.29; H, 3.52; N, 11.10.
4-(2-Methoxyphenyl)-6-nitro-2-(1-(phenylsulfonyl)-1H-
pyrrolo[2,3-b]pyridin-3-yl)quinoline (5i). Isolated as orange solid:
1
mp 237−239 °C; H NMR (400 MHz, DMSO-d6) δ 3.72 (s, 3H,
−OCH3), 7.25 (t, J = 7.6 Hz, 1H, Ar−H), 7.34 (d, J = 8.4 Hz, 1H, Ar−
H), 7.49−7.52 (m, 2H, Ar−H), 7.65 (t, J = 7.6 Hz, 3H, Ar−H), 7.75
(t, J = 7.6 Hz, 1H, Ar−H), 8.21 (d, J = 7.2 Hz, 2H, Ar−H), 8.31
(s, 1H, Ar−H), 8.35 (d, J = 9.2 Hz, 1H, Ar−H), 8.45−8.50 (m, 3H,
Ar−H), 9.20 (s, 1H, Ar−H), 9.27 (d, J = 7.6 Hz, 1H, Ar−H); 13C
NMR (100 MHz, DMSO-d6) δ 56.1, 112.3, 118.4, 120.8, 121.1, 121.5,
122.2, 123.1, 123.4, 125.0, 125.2, 128.2, 129.8, 130.2, 131.5, 131.6,
131.8, 133.2, 135.5, 137.7, 145.0, 146.1, 147.7, 148.4, 150.2, 156.5,
156.7; UPLC (M + 1) 537.4. Anal. Calcd for C29H20N4O5S: C, 64.92;
H, 3.76; N, 10.44. Found: C, 64.87; H, 3.72; N, 10.38.
4-Cyclohexenyl-6-methoxy-2-(1-(phenylsulfonyl)-1H-
pyrrolo[2,3-b]pyridin-3-yl)quinoline (5d). Isolated as orange
1
solid: mp 231−233; °C H NMR (400 MHz, CDCl3) δ 1.83−1.87
(m, 2H), 1.89−1.94 (m, 2H), 2.34−2.35 (m, 2H), 2.45−2.46 (m, 2H),
3.94 (s, 3H, −OMe), 5.93 (bs, 1H, −CH), 7.27−7.39 (m, 3H, Ar−H),
7.49 (t, J = 8.0 Hz, 2H, Ar−H),7.56−7.60 (m, 2H, Ar−H), 8.05
(bs, 1H, Ar−H), 8.25−8.31 (m, 3H, Ar−H), 8.51 (dd, J = 4.8, 1.6 Hz,
1H, Ar−H), 9.05 (bs, 1H, Ar−H); 13C NMR (100 MHz, CDCl3) δ
22.1, 23.0, 25.5, 30.1, 55.5, 104.0, 117.5, 119.7, 119.9, 121.4, 121.7,
124.7, 126.5, 128.0, 128.8, 129.0, 131.1, 132.3, 134.2, 135.8, 138.2,
144.5, 145.5, 147.9, 149.9, 150.7, 157.5; UPLC (M + 1) 496.4. Anal.
Calcd for C29H25N3O3S: C, 70.28; H, 5.08; N, 8.48. Found: C, 70.24;
H, 5.05; N, 8.52.
4-Phenyl-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-
yl)quinoline-6-carbonitrile (5j). Isolated as off white solid: mp
236−238 °C; 1H NMR (400 MHz, CDCl3) δ 7.38 (dd, J = 8.0, 4.8 Hz,
1H, Ar−H), 7.49−7.56 (m, 4H, Ar−H), 7.59−7.65 (m, 4H, Ar−H),
7.86−7.89 (m, 2H, Ar−H), 8.27−8.29 (m, 4H, Ar−H), 8.46 (s, 1H,
Ar−H), 8.55 (dd, J = 4.4, 1.2 Hz, 1H, Ar−H), 9.13 (dd, J = 8.0, 1.2 Hz,
1H, Ar−H); 13C NMR (100 MHz, CDCl3) δ 109.7, 118.6, 118.9,
120.0, 120.2, 121.2, 125.2, 126.7, 128.3, 129.2, 129.3, 129.4, 129.5,
3-(6-Methyl-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-
3-yl)quinolin-4-yl)phenol (5e). Isolated as orange solid: mp 214−
216 °C; 1H NMR (400 MHz, DMSO-d6) δ 2.44 (s, 3H, −CH3), 6.95
(dd, J = 8.0, 2.0 Hz, 1H, Ar−H), 6.99 (s, 1H, Ar−H), 7.03 (d, J =
7.6 Hz, 1H, Ar−H), 7.40 (t, J = 8.0 Hz, 1H, Ar−H), 7.47 (dd, J = 8.0,
1473
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130.5, 130.9, 132.3, 132.4, 134.4, 136.5, 137.8, 145.9, 147.8, 149.6,
149.7, 154.9; UPLC (M + 1) 487.4. Anal. Calcd for C29H18N4O2S: C,
71.59; H, 3.73; N, 11.52. Found: C, 71.50; H, 3.68; N, 11.47.
6-Bromo-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-
yl)-4-(thiophen-3-yl)quinoline (5k). Isolated as off white solid: mp
239−241 °C; 1H NMR (400 MHz, CDCl3) δ 7.48−7.50 (m, 2H, Ar−
H), 7.50 (t, J = 7.6 Hz, 2H, Ar−H), 7.57−7.61 (m, 3H, Ar−H), 7.79
(s, 1H, Ar−H), 7.80 (dd, J = 7.6, 2.4 Hz, 1H, Ar−H), 8.05(d, J = 8.8
Hz, 1H, Ar−H), 8.18 (d, J = 2.0 Hz, 1H, Ar−H), 8.27 (d, J = 8.4 Hz,
2H, Ar−H), 8.38 (s, 1H, Ar−H), 8.52 (dd, J = 4.8, 1.6 Hz, 1H, Ar−H),
9.09 (dd, J = 8.0, 1.6 Hz, 1H, Ar−H), 13C NMR (100 MHz, CDCl3)
δ 119.1, 119.3, 119.8, 120.5, 121.4, 125.4, 125.7, 126.8, 126.9, 127.8,
128.2, 128.6, 129.0, 131.3, 132.4, 133.2, 134.3, 137.7, 138.0, 143.0,
145.7, 147.3, 147.9, 152.6; UPLC (M + 1) 548.3. Anal. Calcd for
C26H16BrN3O2S2: C, 57.15; H, 2.95; N, 7.69. Found: C, 57.08; H,
2.99; N, 7.62.
2-(1-(Phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-4-(thio-
phen-3-yl)benzo[h]quinoline (5l). Isolated as off white solid: mp
218−220 °C; 1H NMR (400 MHz, CDCl3) δ 7.44−7.63 (m, 7H, Ar−
H), 7.73−7.77 (m, 3H, Ar−H), 7.81−7.98 (m, 3H, Ar−H), 8.29 (dd,
J = 1.4 Hz, 2H, Ar−H), 8.42 (s, 1H, Ar−H), 8.58 (dd, J = 4.8, 1.6 Hz,
1H, Ar−H), 9.21 (dd, J = 8.0, 1.6 Hz, 1H, Ar−H), 9.41 (d, J = 8.2 Hz,
1H, Ar−H); 13C NMR (100 MHz, CDCl3) δ 119.0, 119.4, 119.6,
121.2, 122.4, 122.9, 124.4, 124.6, 124.7, 126.0, 126.7, 127.0, 127.4,
127.7, 127.9, 128.6, 128.7, 131.2, 131.6, 133.3, 133.8, 137.7, 138.4,
143.5, 145.2, 146.5, 147.5, 150.3; UPLC (M + 1) 518.4. Anal. Calcd
for C30H19N3O2S2: C, 69.61; H, 3.70; N, 8.12. Found: C, 69.55; H,
3.75; N, 8.07.
239−241 °C; 1H NMR (400 MHz, CDCl3) δ 7.01−7.13 (m, 3H, Ar−H),
7.33−7.59 (m, 6H, Ar−H), 7.81 (s, 1H, Ar−H), 7.90 (d, J = 7.4 Hz,
2H, Ar−H), 8.08 (d, J = 8.4 Hz, 1H, Ar−H), 8.26 (d, J = 7.6 Hz, 2H,
Ar−H), 8.40 (s, 1H, Ar−H), 8.55 (d, J = 4.8 Hz, 1H, Ar−H), 9.58
(d, 1H, J = 8.0 Hz); Sample is not sufficiently soluble to record
13C NMR spectrum; UPLC (M + 1) 558.3. Calcd for C28H18BrN3O3S:
C, 60.44; H, 3.26; N, 7.55. Found: C, 60.49; H, 3.21; N, 7.50.
8-Nitro-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-
4-(thiophen-3-yl)quinoline (5q). Isolated as orange solid: mp 246−
1
248 °C; H NMR (400 MHz, CDCl3) δ 7.39−7.42 (m, 2H, Ar−H),
7.48−7.63 (m, 6H, Ar−H), 7.92 (s, 1H, Ar−H), 8.05 (d, J = 7.6 Hz,
1H, Ar−H), 8.25 (t, J = 8.4 Hz, 3H, Ar−H), 8.42 (s, 1H, Ar−H), 8.52
(d, J = 4.8 Hz, 1H, Ar−H), 9.09 (d, J = 7.6 Hz, 1H, Ar−H); 13C NMR
(100 MHz, CDCl3) δ 118.8, 119.7, 120.5, 121.3, 123.9, 124.7, 125.8,
126.3, 127.2, 128.2, 128.5, 129.1, 129.8, 133.0, 134.4, 137.3, 137.9,
144.1, 146.0, 148.3, 154.4, 160.0, 164.2, 166.6; UPLC (M + 1) 513.2.
Calcd for C26H16N4O4S2: C, 60.93; H, 3.15; N, 10.93. Found: C,
60.82; H, 3.11; N, 10.85.
4-(4-Ethylphenyl)-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]-
pyridin-3-yl)-8-(trifluoromethyl)quinoline (5r). Isolated as off
1
white solid: mp 205−207 °C; H NMR (400 MHz, CDCl3) δ 1.37
(t, J = 7.6 Hz, 3H), 2.82 (q, J = 7.6 Hz, 2H), 7.39−7.52 (m, 8H, Ar−
H), 7.59 (t, J = 6.8 Hz, 1H, Ar−H), 7.86 (s, 1H, Ar−H), 8.09 (d, 1H,
J = 7.6 Hz), 8.14 (d, 1H, J = 6.8 Hz), 8.26 (d, J = 7.6 Hz, 2H, Ar−H),
8.41 (s, 1H, Ar−H), 8.53 (dd, J = 4.8, 1.6 Hz, 1H, Ar−H), 9.33 (dd,
J = 8.0, 1.6 Hz, 1H, Ar−H); 13C NMR (100 MHz, CDCl3) δ 15.2,
28.3, 118.8, 118.9, 119.8, 121.1, 124.2, 125.6, 125.8, 126.2, 127.6,
127.7, 127.8, 127.9, 128.7, 129.1, 130.1, 132.5, 133.9, 134.3, 137.6,
144.7, 144.8, 145.4, 147.5, 148.9, 152.3; LCMS (M + 1) 558.2. Calcd
for C31H22F3N3O2S: C, 66.78; H, 3.98; N, 7.54. Found: C, 66.71; H,
3.93; N, 7.60.
4-Cyclohexenyl-8-methoxy-2-(1-(phenylsulfonyl)-1H-
pyrrolo[2,3-b]pyridin-3-yl)quinoline (5m). Isolated as orange
1
solid: mp 230−232 °C; H NMR (400 MHz, CDCl3) δ 1.81−1.84
(m, 2H), 1.87−1.91 (m, 2H), 2.32−2.33 (m, 2H), 2.44−2.45 (m, 2H),
4.10 (s, 3H, −OMe), 5.90 (t, 1H, J = 1.6 Hz, −CH), 7.05 (d, J =
8.0 Hz, 1H, Ar−H), 7.34−7.48 (m, 5H, Ar−H), 7.55 (t, J = 1.2 Hz,
1H, Ar−H), 7.60 (s, 1H, Ar−H), 8.21 (d, 2H, J = 8.0 Hz, Ar−H), 8.31
(s, 1H, Ar−H), 8.50 (dd, J = 4.8, 1.6 Hz, 1H, Ar−H), 9.05 (dd, J =
8.0, 1.6 Hz, 1H, Ar−H); 13C NMR (100 MHz, CDCl3) δ 21.6,
22.5, 25.0, 29.9, 55.7, 107.4, 116.9, 117.3, 119.6, 120.1, 121.6, 124.5,
125.5, 126.3, 127.6, 128.5, 128.6, 132.0, 133.7, 135.4, 137.7, 140.0,
145.1, 147.6, 150.4, 151.5, 155.3; UPLC (M + 1) 496.4. Anal. Calcd
for C29H25N3O3S: C, 70.28; H, 5.08; N, 8.48. Found: C, 70.21; H,
5.02; N, 8.54.
5-Methoxy-4-phenyl-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-
b]pyridin-3-yl)quinoline (5s). Isolated as orange solid: mp 220−
1
223 °C; H NMR (400 MHz, CDCl3) δ 4.02 (s, 3H, −OMe), 7.11
(dd, J = 8.4, 2.0 Hz, 1H, Ar−H), 7.37 (dd, J = 7.6, 4.8 Hz, 1H, Ar−H),
7.48−7.62 (m, 10H, Ar−H), 7.80 (d, J = 8.8 Hz, 1H, Ar−H), 8.25
(d, J = 8.0 Hz, 2H, Ar−H), 8.34(s, 1H, Ar−H), 8.53(d, J = 4.4 Hz, 1H,
Ar−H), 9.09 (d, J = 8.0 Hz, 1H, Ar−H); Sample is not sufficiently
soluble to record 13C NMR spectrum; UPLC (M + 1) 492.4. Anal.
Calcd for C29H21N3O3S: C, 70.86; H, 4.31; N, 8.55. Found: C, 70.92; H,
4.28; N, 8.49.
7-Methoxy-4-phenyl-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-
b]pyridin-3-yl)quinoline (5s′). Isolated as orange solid: mp 214−
4-(2-Methoxyphenyl)-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-
1
b]pyridin-3-yl)quinoline-8-carbonitrile (5n). Isolated as orange
216 °C; H NMR (400 MHz, CDCl3) δ 3.55 (s, 3H, −OMe), 7.14
1
solid: mp 218−220 °C; H NMR (400 MHz, CDCl3) δ 3.75 (s, 3H,
(dd, J = 9.2, 2.8 Hz, 1H, Ar−H), 7.37 (dd, J = 7.6, 6.4 Hz, 1H, Ar−H),
7.48−7.62 (m, 10H, Ar−H), 7.83 (d, J = 8.4 Hz, 1H, Ar−H), 8.24
(d, J = 8.0 Hz, 2H, Ar−H), 8.32 (s, 1H, Ar−H), 8.52 (dd, J = 4.8,
1.6 Hz, 1H, Ar−H), 9.12 (d, J = 8.0 Hz, 1H, Ar−H); Sample is not
sufficiently soluble to record 13C NMR spectrum; UPLC (M + 1)
492.4. Anal. Calcd for C29H21N3O3S: C, 70.86; H, 4.31; N, 8.55.
Found: C, 70.78; H, 4.35; N, 8.51.
OMe), 7.11−7.20 (m, 3H, Ar−H), 7.33−7.60 (m, 6H, Ar−H), 7.82
(d, J = 8.4 Hz, 1H, Ar−H), 7.87 (s, 1H, Ar−H), 8.10 (d, J = 7.2 Hz,
1H, Ar−H), 8.26 (d, J = 8.0 Hz, 2H, Ar−H), 8.42 (s, 1H, Ar−H), 8.54
(d, J = 8.6 Hz, 1H, Ar−H), 9.55 (d, J = 8.2 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 55.5, 111.2, 112.7, 118.1, 118.9, 120.6, 120.7,
121.0, 121.4, 124.9, 125.6, 126.2, 126.3, 128.2, 129.1, 130.7, 131.0,
131.4, 133.6, 134.4, 135.2, 137.9, 145.8, 145.9, 147.1, 147.8, 154.2,
156.6; UPLC (M + 1) 517.2. Calcd for C30H20N4O3S: C, 69.75; H,
3.90; N, 10.85. Found: C, 69.81; H, 3.84; N, 10.91.
4-(Biphenyl-4-yl)-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]-
pyridin-3-yl)quinoline-5-carbonitrile (5t). Isolated as off white
1
solid: mp 228−230 °C; H NMR (400 MHz, CDCl3) δ 7.27−7.61
(m, 9H, Ar−H), 7.73−7.81 (m, 5H, Ar−H), 7.86 (s, 1H, Ar−H), 7.97
(d, J = 7.2 Hz, 1H, Ar−H), 8.28 (d, J = 8.0 Hz, 2H, Ar−H), 8.45
(s, 1H, Ar−H), 8.50 (d, J = 8.4 Hz, 1H, Ar−H),8.55 (dd, J = 4.8,
1.6 Hz, 1H, Ar−H), 9.12 (d, J = 8.0 Hz, 1H, Ar−H); Sample was not
sufficiently soluble to record 13C NMR spectrum; UPLC (M + 1)
563.5. Anal. Calcd for C35H22N4O2S: C, 74.71; H, 3.94; N, 9.96.
Found: C, 74.65; H, 3.89; N, 9.99.
8-Chloro-4-cyclohexenyl-2-(1-(phenylsulfonyl)-1H-pyrrolo-
[2,3-b]pyridin-3-yl)quinoline (5o). Isolated as orange solid: mp
1
226−228 °C; H NMR (400 MHz, CDCl3) δ 1.80−1.85 (m, 2H),
1.88−1.94 (m, 2H), 2.32−2.34 (m, 2H), 2.42−2.44 (m, 2H), 5.91 (bs,
1H, −CH), 7.37−7.41 (m, 2H, Ar−H), 7.49 (t, J = 8.0 Hz, 2H, Ar−
H), 7.58 (t, J = 7.6 Hz, 1H, Ar−H), 7.66 (s, 1H, Ar−H), 7.82 (d, 1H,
J = 8.4 Hz, Ar−H), 7.92 (d, 1H, J = 8.4 Hz, Ar−H), 8.25 (d, J =
8.4 Hz, 2H, Ar−H), 8.38 (s, 1H, Ar−H), 8.52 (dd, J = 4.8, 1.6 Hz, 1H,
Ar−H), 9.05 (dd, J = 8.0, 1.6 Hz, 1H, Ar−H); 13C NMR (100 MHz,
CDCl3) δ 21.9, 22.9, 25.4, 30.4, 117.4, 119.7, 120.2, 121.6, 124.6,
125.5, 125.6, 127.0, 128.1, 129.0, 129.5, 129.6, 133.3, 133.9, 134.3,
135.3, 138.1, 144.7, 145.7, 147.9, 152.4, 152.6; UPLC (M + 1) 500.4.
Anal. Calcd for C28H22ClN3O2S: C, 67.26; H, 4.43; N, 8.40. Found: C,
67.20; H, 4.39; N, 8.33.
4-(Biphenyl-4-yl)-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]-
pyridin-3-yl)quinoline-7-carbonitrile (5t′). Isolated as off white
1
solid: mp 210−211 °C; H NMR (400 MHz, CDCl3) δ 7.27−7.36
(m, 1H, Ar−H), 7.47 (d, J = 7.6 Hz, 1H, Ar−H), 7.51 (d, J = 6.8 Hz,
2H, Ar−H), 7.55 (d, J = 6.8 Hz, 2H, Ar−H), 7.60−7.68 (m, 3H,
Ar−H), 7.74 (d, J = 8.4 Hz, 2H, Ar−H), 7.90 (d, J = 8.0 Hz, 2H,
Ar−H), 7.93 (s, 1H, Ar−H), 8.11 (d, J = 8.8 Hz, 2H, Ar−H), 8.30 (d, J =
7.6 Hz, 2H, Ar−H), 8.50 (s, 1H, Ar−H), 8.56 (dd, J = 4.8, 1.6 Hz,
1H, Ar−H), 8.65 (d, J = 0.8 Hz, 1H, Ar−H), 9.11(dd, J = 8.0, 1.6 Hz,
3-(8-Bromo-2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-
3-yl)quinolin-4-yl)phenol (5p). Isolated as off white solid: mp
1474
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1H, Ar−H); Sample is not sufficiently soluble to record 13C NMR
spectrum; UPLC (M + 1) 563.5. Anal. Calcd for C35H22N4O2S: C,
74.71; H, 3.94; N, 9.96. Found: C, 74.66; H, 3.97; N, 9.99.
Anal. Calcd for C32H22N4O2S: C, 72.98; H, 4.21; N, 10.64. Found: C,
72.89; H, 4.25; N, 10.59.
6-Methoxy-4-phenyl-2-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
quinoline (6b). Isolated as pale brown solid: mp 248−250 °C;
(1H NMR 400 MHz, DMSO-d6) 3.75 (s, 3H, −OCH3), 7.24−7.27
(m, 2H, Ar−H), 7.43 (d, J = 8.0 Hz, 1H, Ar−H), 7.54−7.67 (m, 5H,
Ar−H), 7.98 (s, 1H, Ar−H), 8.08 (d, J = 9.2 Hz, 1H, Ar−H), 8.32
(d, J = 4.0 Hz, 1H, Ar−H), 8.52 (s, 1H, Ar−H), 9.17 (d, J = 7.2 Hz,
1H, Ar−H), 12.10 (br s, 1H, −NH); 13C NMR (100 MHz, DMSO-d6)
δ 55.6, 104.4, 114.7, 117.1, 118.5, 119.5, 121.4, 125.5, 127.9, 128.9,
129.2, 129.8, 131.1, 131.2, 138.4, 143.8, 144.6, 146.8, 149.9, 152.9,
157.1; UPLC (M + 1) 352.3. Anal. Calcd for C23H17N3O: C, 78.61; H,
4.88; N, 11.96. Found: C, 78.53; H, 4.83; N, 11.99.
6-Methoxy-4-(2-methoxyphenyl)-2-(1H-pyrrolo[2,3-b]-
pyridin-3-yl)quinoline (6c). Isolated as brown solid: mp 232−
235 °C; (1H NMR 400 MHz, CDCl3) 3.85 (s, 6H, −OCH3), 6.87
(d, J = 2.8 Hz, 1H, Ar−H), 7.13−7.53 (m, 6H, Ar−H), 7.71 (s, 1H,
Ar−H), 8.02 (s, 1H, Ar−H), 8.13 (d, J = 8.8 Hz, 1H, Ar−H), 8.42 (dd,
J = 4.8, 1.4 Hz, 1H, Ar−H), 9.14 (dd, J = 8.0, 1.4 Hz, 1H, Ar−H),
11.56 (br s, 1H, −NH); 13C NMR (100 MHz, CDCl3) δ 55.4, 55.6,
104.5, 111.2, 116.3, 118.7, 119.2, 120.2, 120.8, 121.2, 124.9, 126.6,
127.4, 129.8, 130.8, 131.3, 131.6, 143.2, 144.5, 144.6, 149.6, 151.9,
156.8, 156.9; UPLC (M + 1) 382.3. Anal. Calcd for C24H19N3O2: C,
75.57; H, 5.02; N, 11.02. Found: C, 75.63; H, 4.97; N, 10.97.
4-Cyclohexenyl-6-methoxy-2-(1H-pyrrolo[2,3-b]pyridin-3-
yl)quinoline (6d). Isolated as orange solid: mp 224−226 °C;
(1H NMR 400 MHz, DMSO-d6) 1.76−1.77 (m, 2H), 1.84−1.95
(m, 2H), 2.29−2.43 (m, 4H), 3.83 (s, 3H, −OMe), 5.90 (bs, 1H,
−CH), 7.21−7.30 (m, 3H, Ar−H), 7.39 (d, J = 9.0 Hz, 1H, Ar−H),
7.81 (s, 1H, Ar−H), 7.99 (d, J = 8.0 Hz, 1H, Ar−H), 8.30 (d, J = 3.2
Hz, 1H, Ar−H), 8.48 (d, J = 2.4 Hz, 1H, Ar−H), 9.12 (d, J = 6.8 Hz,
1H, Ar−H); 13C NMR (100 MHz, DMSO-d6) δ 22.0, 22.9, 25.3, 29.9,
55.7, 104.5, 114.7, 117.2, 117.3, 118.5, 121.1, 125.4, 127.2, 128.6,
131.0, 131.3, 135.7, 143.8, 144.4, 149.4, 149.8, 152.7, 156.8; UPLC
(M + 1) 356.3. Anal. Calcd for C23H21N3O: C, 77.72; H, 5.96; N,
11.82. Found: C, 77.79; H, 6.01; N, 11.76.
4-(2-Methoxyphenyl)-5-nitro-2-(1-(phenylsulfonyl)-1H-
pyrrolo[2,3-b]pyridin-3-yl)quinoline (5u). Isolated as pale yellow
1
solid: mp 198−200 °C; H NMR (400 MHz, CDCl3) δ 3.71 (s, 3H,
−OMe), 6.99 (d, J = 8.4 Hz, 1H, Ar−H), 7.14 (t, J = 7.4 Hz, 1H, Ar−
H), 7.34−7.39 (m, 2H, Ar−H), 7.47−7.62 (m, 4H, Ar−H), 7.74 (t, J =
7.6 Hz, 1H, Ar−H), 7.75 (d, J = 7.6 Hz, 1H, Ar−H), 7.79 (s, 1H, Ar−
H), 8.27 (d, J = 7.6 Hz, 2H, Ar−H), 8.40 (d, J = 7.4 Hz, 1H, Ar−H),
8.41 (s, 1H, Ar−H), 8.54 (d, J = 4.2 Hz, 1H, Ar−H), 9.12 (d, J = 7.8
Hz, 1H, Ar−H); 13C NMR (100 MHz, CDCl3) δ 54.8, 110.2, 117.9,
118.2, 119.5, 120.5, 120.8, 122.1, 123.4, 125.9, 126.3, 127.2, 127.8,
128.7, 129.3, 130.2, 131.9, 133.9, 134.0, 137.4, 143.1, 145.4,
147.4, 148.4, 148.5, 153.0, 155.3; UPLC (M + 1) 537.4. Calcd for
C29H20N4O5S: C, 64.92; H, 3.76; N, 10.44. Found: C, 64.88; H, 3.70;
N, 10.41.
4-(2-Methoxyphenyl)-7-nitro-2-(1-(phenylsulfonyl)-1H-
pyrrolo[2,3-b]pyridin-3-yl)quinoline (5u′). Isolated as yellow
solid: mp 194−197 °C; 1H NMR (400 MHz, CDCl3) δ 3.76 (s,
3H, −OMe), 7.14 (d, J = 8.4 Hz, 1H, Ar−H), 7.20 (t, J = 7.6 Hz, 1H,
Ar−H), 7.36 (dd, J = 7.4, 1.6 Hz, 1H, Ar−H), 7.42 (dd, J = 8.0, 4.8 Hz,
1H, Ar−H), 7.50−7.64 (m, 4H, Ar−H), 7.74 (d, J = 9.2 Hz, 1H, Ar−
H), 7.89 (s, 1H, Ar−H), 8.18 (dd, J = 9.2, 2.4 Hz, 1H, Ar−H), 8.28
(d, J = 7.4 Hz, 2H, Ar−H), 8.42 (s, 1H, Ar−H), 8.56 (dd, J = 4.8,
1.6 Hz, 1H, Ar−H), 9.08 (d, J = 2.4 Hz, 1H, Ar−H), 9.20 (dd, J = 8.0,
1.6 Hz, 1H, Ar−H); 13C NMR (100 MHz, CDCl3) δ 55.5, 111.3,
117.8, 119.4, 120.0, 121.1, 121.2, 122.4, 124.8, 125.2, 127.0, 128.2,
128.3, 129.1, 129.6, 131.0, 131.1, 132.2, 134.4, 137.8, 146.0, 146.6,
147.5, 147.7, 148.3, 154.2, 156.5; UPLC (M + 1) 537.4. Calcd for
C29H20N4O5S: C, 64.92; H, 3.76; N, 10.44%. Found: C, 64.81; H,
3.71; N, 10.50.%.
2-(1-(Phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-4-(thio-
phen-3-yl)-5-(trifluoromethyl)quinoline (5v). Isolated as orange
1
solid: mp 240−242 °C; H NMR (400 MHz, CDCl3) δ 7.22 (d, J =
4.8 Hz, 1H, Ar−H), 7.33−7.44 (m, 3H, Ar−H), 7.51 (dd, J = 9.6, 1.6,
Hz, 2H, Ar−H), 7.59 (t, J = 1.4 Hz, 1H, Ar−H), 7.74 (s, 1H, Ar−H),
7.78 (t, J = 7.8 Hz, 1H, Ar−H), 7.98 (d, J = 7.4 Hz, 1H, Ar−H), 8.27
(dd, J = 7.6, 1.4 Hz, 2H, Ar−H), 8.37 (s, 1H, Ar−H), 8.40 (d, J =
7.4 Hz, 1H, Ar−H), 8.54 (dd, J = 4.6, 1.6 Hz, 1H, Ar−H), 9.12 (dd,
J = 8.0, 1.6 Hz, 1H, Ar−H); 13C NMR (100 MHz, CDCl3) δ 118.3,
119.8, 121.3, 123.2, 123.3, 124.6, 126.0, 127.5, 127.6, 127.7,
127.9, 128.2, 129.1, 129.2, 132.3, 134.3, 135.0, 137.9, 140.4, 140.5,
143.6, 145.8, 147.8, 149.7, 151.9; UPLC (M + 1) 536.3. Calcd for
C27H16F3N3O2S2: C, 60.55; H, 3.01; N, 7.85. Found: C, 60.48; H,
3.06; N, 7.80.
4-Phenyl-2-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinoline-6-
carbonitrile (6j). Isolated as brown solid: mp 253−255 °C; (1H
NMR 400 MHz, DMSO-d6) 7.30 (dd, J = 7.6, 4.8 Hz, 1H, Ar−H),
7.61−7.63 (m, 5H, Ar−H), 8.02−8.36 (m, 5H, Ar−H), 8.75 (s, 1H, Ar−
H), 9.20 (d, J = 8.0 Hz, 1H, Ar−H), 12.36 (br s, 1H, −NH); 13C NMR
(100 MHz, DMSO-d6) δ 107.9, 114.2, 117.7, 118.5, 119.5, 120.5,
124.4, 129.4,* 130.1, 130.6, 130.9,* 131.5, 131.9, 136.9, 144.3, 148.3,
150.0, 150.1, 157.9; UPLC (M + 1) 347.3. Anal. Calcd for C23H14N4:
C, 79.75; H, 4.07; N, 16.17. Found: C, 79.68; H, 4.12; N, 16.24 (* two
carbons merged here).
4-(2-Methoxyphenyl)-2-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
quinoline-8-carbonitrile (6n). Isolated as yellow solid: mp 262−
264 °C; (1H NMR 400 MHz, DMSO-d6) 3.69 (s, 3H, −OCH3), 7.16−
7.68 (m, 7H, Ar−H), 8.19 (s, 1H, Ar−H), 8.28−8.36 (m, 2H, Ar−H), 8.75
(s, 1H, Ar−H), 9.43 (d, J = 7.6 Hz, 1H, Ar−H), 12.35 (br s, 1H,
−NH); 13C NMR (100 MHz, DMSO-d6) δ 55.9, 111.2, 112.0,
114.2, 117.8, 118.6, 118.8, 121.0, 121.3, 125.2, 125.5, 125.9,* 130.4,
131.0, 131.4, 131.6, 135.9, 144.4, 146.6, 148.3, 150.1, 156.9, 157.0;
UPLC (M + 1) 377.3. Anal. Calcd for C24H16N4O: C, 76.58; H,
4.28; N, 14.88. Found: C, 76.51; H, 4.32; N, 14.83 (* two carbons
merged here).
6-Methoxy-4-phenyl-2-(1H-pyrrolo[2,3-b]pyridin-2-yl)-
quinoline (8). Isolated as pale yellow solid: mp 212−214 °C;
(1H NMR 400 MHz, DMSO-d6) 3.78 (s, 3H, −OCH3), 7.11 (dd, J =
7.8, 4.6 Hz, 1H, Ar−H) 7.20 (d, J = 2.8 Hz, 1H, Ar−H), 7.39 (d, J =
2.0 Hz, 1H, Ar−H), 7.51 (dd, J = 9.2, 2.8 Hz, 1H, Ar−H), 7.58−7.72
(m, 5H, Ar−H), 8.02 (d, J = 6.8 Hz, 1H, Ar−H), 8.10 (d, J = 9.2 Hz,
1H, Ar−H), 8.14 (s, 1H, Ar−H), 8.30 (dd, J = 4.6, 1.4 Hz, 1H,
Ar−H), 12.26 (br s, 1H, −NH); sample was not sufficiently soluble
to record 13C NMR spectrum; UPLC (M + 1) 352.3. Anal. Calcd
for C23H17N3O: C, 78.61; H, 4.88; N, 11.96. Found: C, 78.56; H, 4.81;
N, 11.92.
2-(1-(Phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-4-(thio-
phen-3-yl)-7-(trifluoromethyl)quinoline (5v′). Isolated as orange
1
solid: mp 225−227 °C; H NMR (400 MHz, CDCl3) δ 7.38−7.42
(m, 2H, Ar−H), 7.52 (t, J = 7.8 Hz, 2H, Ar−H), 7.59−7.69 (m, 4H,
Ar−H), 7.90 (s, 1H, Ar−H), 8.18 (d, J = 8.8 Hz, 1H, Ar−H), 8.29
(d, J = 8.0 Hz, 2H, Ar−H), 8.42 (s, 1H, Ar−H), 8.49 (s, 1H, Ar−H),
8.55 (d, J = 4.6 Hz, 1H, Ar−H), 9.18 (d, J = 8.0 Hz, 1H, Ar−H); 13C
NMR (100 MHz, CDCl3) δ 118.5, 119.5, 119.7, 120.9, 121.5, 125.0,
125.5, 126.5, 126.6, 126.8, 127.0, 127.1, 127.8, 128.2, 128.7, 130.9,
131.2, 132.1, 133.9, 137.2, 143.4, 145.5, 147.4, 147.5, 153.3; UPLC
(M + 1) 536.3. Calcd for C27H16F3N3O2S2: C, 60.55; H, 3.01; N,
7.85. Found: C, 60.51; H, 2.97; N, 7.90.
2-(1-(Phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-4-p-
tolyl-1,10-phenanthroline (5x). Isolated as orange solid: mp 267−
269 °C; (1H NMR 400 MHz, CDCl3) 2.53 (s, 3H, −CH3), 7.42−7.59
(m, 8H, Ar−H), 7.66 (dd, J = 8.0, 4.4 Hz, 1H, Ar−H), 7.73 (d, J =
9.0 Hz, 1H, Ar−H), 7.95 (d, J = 7.8 Hz, 1H, Ar−H), 7.96 (s, 1H, Ar−
H), 8.22−8.27 (m, 3H, Ar−H), 8.42 (s, 1H, Ar−H), 8.55 (dd, J = 4.8,
1.6 Hz, 1H, Ar−H), 9.25 (dd, J = 4.4, 1.6 Hz, 1H, Ar−H), 9.48 (dd,
J = 8.0, 1.6 Hz, 1H, Ar−H); 13C NMR (100 MHz, CDCl3) δ 21.4,
120.3, 120.5, 120.7, 122.2, 123.1, 124.2, 125.2, 125.6, 125.9, 128.0,
128.6, 129.0, 129.5, 129.6, 132.8, 134.2, 135.0, 135.8, 138.2, 138.6,
145.6, 146.4, 146.7, 148.0, 149.4, 150.5, 151.8; UPLC (M + 1) 527.4.
6-Methoxy-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4-
phenylquinoline (10). Isolated as orange solid: mp 195−197 °C;
(1H NMR 400 MHz, DMSO-d6) 3.75 (s, 3H, −NCH3), 3.89
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The Journal of Organic Chemistry
Article
(s, 3H, −OCH3), 7.13 (d, J = 2.4 Hz, 1H, Ar−H), 7.29 (dd, J = 7.6, 4.4
Hz, 1H, Ar−H), 7.43 (dd, J = 9.2, 2.4 Hz, 1H, Ar−H), 7.54−7.67 (m,
5H, Ar−H), 7.89 (s, 1H, Ar−H), 8.07 (d, J = 9.2 Hz, 1H, Ar−H), 8.37
(d, J = 4.4 Hz, 1H, Ar−H), 8.57 (s, 1H, Ar−H), 9.14 (d, J = 7.6 Hz,
1H, Ar−H); 13C NMR spectrum could not be recorded due to poor
solubility; UPLC (M + 1) 366.4. Anal. Calcd for C24H19N3O: C,
78.88; H, 5.24; N, 11.50. Found: C, 78.83; H, 5.28; N, 11.57.
2-(1-Benzyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-6-methoxy-4-
phenylquinoline (11). Isolated as orange solid: mp 205−207 °C;
(1H NMR 400 MHz, CDCl3) 3.81 (s, 3H, −OCH3), 5.60 (s, 2H,
−CH2), 7.16 (d, J = 2.4 Hz, 1H, Ar−H), 7.28−7.59 (m, 12H, Ar−H),
7.61 (s, 1H, Ar−H), 7.84 (s, 1H, Ar−H), 8.12 (d, J = 9.2 Hz, 1H, Ar−
H), 8.45 (dd, J = 4.8, 1.6 Hz, 1H, Ar−H), 9.09 (d, J = 8.0, 1.6 Hz, 1H,
Ar−H); 13C NMR (100 MHz, DMSO-d6) δ 48.0, 55.4, 104.1, 115.4,
117.2, 119.0, 119.3, 121.3, 125.9, 127.5, 127.6, 127.8, 128.3, 128.6,
128.8, 129.3, 131.0, 131.1, 137.4, 138.7, 143.9, 144.9, 147.2, 148.6,
151.8, 157.2; UPLC (M + 1) 442.3. Anal. Calcd for C30H23N3O: C,
81.61; H, 5.25; N, 9.52. Found: C, 81.70; H, 5.20; N, 9.45.
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ASSOCIATED CONTENT
■
S
* Supporting Information
General experimental procedures, H, 13C NMR and mass
1
spectra for synthesized compounds 5a−x, 6b, 6c, 6d, 6j, 6n, 8,
10, and 11, and crystallographic information file (CIF) of 5b.
This material is available free of cost via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: muthumanian2001@yahoo.com.
■
ACKNOWLEDGMENTS
R. Suresh is grateful to Syngene International Limited, Bangalore
for providing necessary facilities to carry out this work.
■
REFERENCES
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