Transition-metal-free access to 7-azaindoles

Article abstract of DOI:10.1016/j.tet.2018.06.025

A novel method for transition-metal-free synthesis of 7-azaindoles is developed through a one-pot synthesis involving amination of pyridine N-oxides and intramolecular enamine formation. Remarkable features of the method include simple operation, mild reaction conditions, wide substrate scope, and easily accessible starting materials.

Full text of DOI:10.1016/j.tet.2018.06.025

Accepted Manuscript
Transition-metal-free access to 7-azaindoles
Dong Wang, Jianyong Hu, Junjie Zhao, Meng Shen, Yuxi Wang, Peng Yu
PII:
S0040-4020(18)30714-2
10.1016/j.tet.2018.06.025
TET 29621
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 6 April 2018
Revised Date: 9 June 2018
Accepted Date: 11 June 2018
Please cite this article as: Wang D, Hu J, Zhao J, Shen M, Wang Y, Yu P, Transition-metal-free access
to 7-azaindoles, Tetrahedron (2018), doi: 10.1016/j.tet.2018.06.025.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Transition-Metal-Free Access to 7-
Azaindoles
Leave this area blank for abstract info.
Dong Wang,* Jianyong Hu, Junjie Zhao, Meng Shen, Yuxi Wang, and Peng Yu*
China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal
Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Transition-Metal-Free Access to 7-Azaindoles
Dong Wang,* Jianyong Hu, Junjie Zhao, Meng Shen, Yuxi Wang, and Peng Yu*
a China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University
of Science & Technology, Tianjin 300457, China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A novel method for transition-metal-free synthesis of 7-azaindoles is developed through a one-
pot synthesis involving amination of pyridine N-oxides and intramolecular enamine formation.
Remarkable features of the method include simple operation, mild reaction conditions, wide
substrate scope, and easily accessible starting materials.
Available online
2009 Elsevier Ltd. All rights reserved
.
Keywords:
7-azaindoles
pyridine N-oxides
N-heterocycles
1. Introduction
Similar to the indole synthesis starting from anilines,
common synthetic strategies to prepare 7-azaindoles rely on
the use of 2-amino-3-halidepyridines as starting material under
the catalysis of Pd or Rh (Scheme 1).6 For example, the Larock
indole synthesis (eq 1),7 Heck (eq 2),8 Suzuki (eq 3),9 C-H
activation/annulative coupling (eq 4),10 Buchwald-Heck (eq
5),11 and Buchwald-Sonogashira method reported by Marques
(eq 6).12 These approaches, however, suffer from limited
substrate scope, harsh reaction conditions, or low yields.
7-Azaindoles, indole bioisosteres, are the key scaffold for
variolins family (Figure 1),1 many of which are potent kinase
inhibitors.2 7-Azaindole frameworks exhibit more favorable
physicochemical properties and enhanced potency than the
corresponding indoles because of the additional nitrogen
atom,3 which serves as efficient hydrogen bond acceptors.
Accordingly, they have been widely used as key scaffolds for
a variety of drug candidates4 and chemical probes.5 There are
one on market drug (vemurafenib, Figure 1) and several drugs
(fevipiprant and pexidartinib) in clinical phase III containing
this structure.
Scheme 1. Synthetic Approaches to 7-Azaindoles.
Figure 1. Representative Bioactive Molecules bearing 7-
Azaindoles.
First, aminopyridines are challenging starting materials in
metal-catalyzed reactions13 due to the strong chelating
properties and the low reactivity. Second, transition-metal-
catalyzed reactions are problematic in terms of their

2
Tetrahedron
ACCEPTED MANUSCRIPT
environmental impact and operational costs.14 On the other
hand, metal-free access to 7-azaindoles has been scarcely
reported.15 The only metal-free method suffers from 3 steps
synthesis, and difficult to access starting material (substituted
2-fluoropyridines). Therefore, the development of new, more
versatile procedures under metal-free conditions is highly
demanded.
temperature (entry 11) or more concentrated conditions (entry
12) led to decreased product yield.
Table 1. Reaction optimization for the Cascade
Amination/Enamine Formation Reactiona.
Due to the electronic-deficient nature of pyridines, the
majority of synthetic approaches to complex pyridine
derivatives largely rely on the manipulation of
prefunctionalized building blocks. Completely different from
the conventional methods, our group has been exploring
reaction conditions that will enable the direct functionalization
of pyridines through substrate design and mechanism study,
utilizing easily accessible pyridine N-oxides as substrates. For
example, concise synthetic methods for azacoumarins16 and
azachromones17 have been established. Herein, we report a
transion-metal-free synthetic method to prepare 7-azaindoles,
from the easily accessible pyridine N-oxides (1) and amines
(2) via a cascade amination of N-oxides/enamine formation
sequence (Scheme 2). It was expected that 1 and 2 would react
to give 4 under PyBrop activation conditions,18 after which the
enamine would be formed to afford 3. To the best of our
knowledge, this general synthetic method based on N-oxides
chemistry is unprecedented.
entry
act.
base
DIEA
NaOAc
solvent
DCM
DCM
[M]
0.25
0.25
yield, %
31
1
2
PyBroP
PyBroP
28
0.25
0.25
0.25
0.20
0.20
0.25
0.25
1.0
3
4
PyBroP
PyBroP
PyBroP
PyBroP
PyBroP
Ac2O
Na2CO3
Na2CO3
Na2CO3
K2CO3
Cs2CO3
Na2CO3
n/a
DCM
THF
42
19
37
56
21
n/a
n/a
n/a
30
49
5
EA
6
DCM
DCM
DCM
PhCF3
THF
7
8b
9 b
10 b
11c
12
Ts2O
BF3
Na2CO3
K2CO3
K2CO3
0.20
0.80
PyBroP
PyBroP
DCE
DCM
a
Unless otherwise noted, all reactions were conducted at 0.20 M
concentration with N-oxide (120 mg, 1.0 equiv), activation agent (1.3
b
equiv), base (3.0 equiv) and 4Å molecular sieves at r.t. 3.0 equiv of
activation agent was used. c Reaction temperature was 85
.
Scheme 2. Transition-Metal-Free Access to 7-Azaindoles.
2. Results and Discussion
In order to establish the reaction conditions, 3-(2-
oxopropyl) pyridine N-oxide (1a) and benzyl amine were
selected
as
model
substrates
using
PyBrop
(bromotripyrrolidinophosphonium hexafluorophosphate) as
activation agent (Table 1). Gratifyingly, the desired product
was formed in 31% yield using DIEA as base and DCM as
solvent (entry 1). Although several byproducts, including the
regioisomeric amination byproduct (3a’), were detected, 3a
could be easily separated by a flash column because its
polarity was much less than other products. It is worth noting
that 4a was not observed, indicating that the enamine
formation reaction is fast. A careful screen of base/solvent pair
(entries 2 to 7) led to the identification of K2CO3/DCM as the
optimum combination for this reaction (56% yield, entry 6).
Those aforementioned byproducts were still produced under
the optimum reaction conditions. The molar ratio of 3a/3a’≈
Scheme 3. Preparation of 3a.
It’s worth noting that 3a was delivered in only 2 steps with
49% overall yield using commercially available 1-(pyridin-3-
yl)propan-2-one (10a), compared with the known method,
which resulted in 30% overall yield after five steps (Scheme
3).20 Besides, this reported procedure requires using very toxic
CuCN. Therefore, this newly developed one-pot reaction is
likely to be a very useful method for the preparation of 7-
azaindoles.
1
6:1 according to H NMR of the crude product. It’s found that
other activation agents, including Ac2O, Ts2O and BF3, are
ineffective for this transformation (entries 8 to 10). Although
Ts2O has been proved to be an effective activation agent for
the amination of pyridine N-oxides,19 no reaction could be
detected for this transformation. Moreover, higher reaction

3
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groups in the pyridine N-oxides part. Furthermore, pyridine
rings carrying ester groups (3u), chloro (3w, 3x), C2- (3aa,
3ab), C3- (3y) and C4- methyl (3z) substituents are compatible
with the reaction, thus providing additional handles for further
functionalization at the halogenated and benzylic positions
using cross coupling reactions or nucleophilic aromatic
substitutions. It seems that the reaction is very sensitive to R2
groups. Low yields were observed for both 3r and 3t, probably
due to steric hindrance. Surprisingly, in sharp contrast to most
electron neutral or poor substrates, the regioisomeric
amination byproduct (3ae’) predominates (59% yield, Scheme
4) for methoxy substituted substrate, indicating that this new
synthetic method is not suitable for those strong EDG
substituted pyridine N-oxides.
Scheme
4.
Substrate
Scope
for
the
Cascade
Amination/Enamine Formation Reactiona.
Scheme 5. Mechanism Investigations. a The ratio is
determined by 1H NMR of the crude product.
In order to determine the reaction sequence of this cascade
transformation, compound 1a was subjected to enamine
formation conditions (Scheme 5a). However, both 1a and
benzyl amine remained in the mixture and no reaction could be
detected. In contrast, the reaction was triggered once PyBrop
was added. Moreover, it has been confirmed that PyBrop
cannot trigger the formation of enamine because no reaction
could be detected with 10a under the reaction conditions
(Scheme 5a). These observations indicate that the amination of
N-oxides occurs first, followed by the intramolecular enamine
formation. Since pyridine N-oxides are known to react via
SEAr in some reactions,21 a competition experiment was
performed to verify if this pathway was operative. Benzyl
amine was reacted in the presence of both electron-rich
pyridine N-oxide (1m) and electron-deficient pyridine N-oxide
(1q) under the standard conditions (Scheme 5b). It was found
that product 3z predominates, indicating a complex reaction
manifold, and the rate-determining step is governed by SEAr.
a Unless otherwise noted, all reactions were conducted at 0.20 M
concentration with N-oxide (1.0 equiv), amines (1.5 equiv),
PyBrop (1.3 equiv), K2CO3 (3.0 equiv) and 4Å molecular sieves
b
in DCM at r.t.
The reaction were conducted at 0.20 M
concentration with N-oxide (1.0 equiv), amines (2.0 equiv),
PyBrop (2.0 equiv), K2CO3 (3.0 equiv) and 4Å molecular sieves
in DCE at reflux.
Based on the above observations and the reactivity of N-
oxides, the proposed mechanism for this transformation is
outlined in Scheme 6. Replacement of the bromine atom of
PyBrop with 1 produces the activated pyridine complex 8.
Nucleophilic attack of amines 2 to the C2 position of 8 yields
With the optimized conditions in hand, we then investigated
the scope of this cascade amination/enamine formation and
found that a variety of pyridine and quinoline N-oxides can be
successfully converted to the desired product in modest to
good yields (up to 91%, Scheme 4). Excellent regioselectivity
(C2 vs. C4) was also observed. With regard to the scope of
amines, ammonia (3b, 3l), alkyl and aryl amines (3g, 3i, 3m)
are all good substrates. Generally, aryl amines afforded better
yields than alkyl amines (i.e., 3i > 3h, 3m > 3n). Moreover,
the reaction works for those steric hindered amines (3f, 3j, 3o),
although slightly lower yields were observed. The reaction can
well tolerate alkyl, cycloalkyl, and aryl groups for R2 and R3
9, followed by basic rearomatization to yield
4 and
phosphoryltripyrrolidine. Nucleophilic attack of the amino
group to the carbonyl group produces 5. Finally, elimination of
water affords product 3.
3. Conclusions
In conclusion, an efficient and tranisition-metal-free
synthesis of 7-azaindoles is developed through a one-pot

4
Tetrahedron
ACCEPTED MANUSCRIPT
operation, involving amination of pyridine N-oxides and
intramolecular enamine formation. The present reaction has
broad substrate scope, including alkyl amines, aryl amines and
pyridines carrying various substituents. Moreover, most of the
substrates required in this methodology, without any C2-amino
group, is cheap and easy to access. The reaction had only
moderate overall yield (46% average yield) but it was
nevertheless remarkably effective given that it generated three
new bonds (~77% average yield per bond formation). This
new method would also refresh strategy to prepare complex
pyridine derivatives via conventional methods.
Scheme 6. Proposed Reaction Mechanism.
4. Experimental section
7~8 with ammonia, then diluted with water and extracted with
EA. The combined organic phase was washed with brine,
dried over Na2SO4, concentrated in vacuo and
chromatographed gradiently on silica gel with PE/EA
(10:1~1:1) to afford the product.
General Remarks. The preparation experiments were
performed under air or an argon atmosphere in oven dried
glassware. Solvents used as reaction media were distilled
immediately before use: THF was distilled from
Na/benzophenone ketyl, DCM and DCE were distilled from
calcium hydride. All reagents were purchased at the highest
commercial quality and used without further purification.
Reactions were monitored by thin layer chromatography
(TLC) using ultra violet light (UV) as the visualizing agent.
Nuclear magnetic resonance spectra (NMR) were recorded on
Bruker AV-400 instruments and were calibrated using residual
undeuterated solvent as an internal reference (1H NMR:
CHC13 7.26 ppm, 13C NMR: CHC13 77.16 ppm). High
resolution mass spectra (HRMS) were recorded on a hybrid
IT-TOF mass spectrometer (Shimadzu LCMS-IT-TOF, Kyoto,
Japan). The following abbreviations were used to indicate
multiplicities: s = singlet, d = doublet, t = triplet, q = quartet,
quin = quintet, sex = sextet, sep = septet, dd = doublet of
doublets, dt = doublet of triplets, ddd = doublet of doublet of
doublets, ddt = doublet of doublet of triplets, m = multiplet).
General Procedure III (for the Preparation of 1a-q):
Compound 10 (1.0 eq) was dissolved in DCM (0.3 M) and
mCPBA (1.2 eq) was added and stirred at room temperature
overnight until the reaction was complete as indicated by TLC.
The reaction mixture was concentrated in vacuo and
chromatographed gradiently on silica gel with DCM/MeOH
(100:1~30:1) to afford product 1.
General Procedure IV (for the Preparation of 3a-ad): To a
solution of compound 1 (1.0 eq.) and compound 2 (1.5 eq.) in
dry DCM (0.2 M) was added K2CO3 (3.0 eq.), 4Å molecular
sieves (same weight as cpd.1), and PyBrop (1.3 eq.) in this
order. The resulting mixture was stirred at r.t. for several hours
until the reaction was complete as indicated by TLC. The
reaction mixture was filtrated. The mother liquor was diluted
with sat. aqueous NH4Cl and extracted with EA. The
combined organic phase was dried over Na2SO4, concentrated
in vacuo and the crude product was purified by flash column
chromatography using PE/EA (50:1~10:1) to afford product 3.
See the Supplenmentary Data for general reaction schemes.
General Procedure I (for the Preparation of 9a-c): To a
stirred solution of compound 8 (1.0 eq.) in deoxygenated DMF
(1 M) was added CuI (0.05 eq.), Et3N (4.0 eq.), alkyne (1.2
eq.) and Pd(PPh3)2Cl2 (0.05 eq.), the resulting mixture was
stirred at r.t. overnight. After filtration through Celite, the
organic layer was diluted with H2O and extracted with DCM.
The combined organic phase was washed with brine, dried
over Na2SO4, filtered and concentrated under reduced pressure
to afford the crude product, which was purified by flash
column chromatography using PE/EA (50:1~10:1) as eluent.
Methyl 5-(phenylethynyl)nicotinate (9a). Following General
Procedure , using methyl 5-bromonicotinate (4 g, 18.516
mmol), phenylacetylene (2.27 g, 22.220 mmol), the title
compound was obtained (4.05 g, 92% yield) as a yellow solid.
The spectroscopic data are consistent with material from
commercial sources. 1H NMR (400 MHz, d6-DMSO) δ 9.04 (s,
1H), 8.97 (s, 1H), 8.37 (s, 1H), 7.62 (d, J = 3.6 Hz, 2H), 7.47
(d, J = 1.6 Hz, 3H), 3.90 (s, 3H). 13C NMR (100 MHz, d6-
DMSO) δ 164.6, 155.2, 149.0, 138.8, 131.7, 129.6, 128.9,
125.5, 121.4, 119.7, 93.5, 85.1, 52.7.
General Procedure II (for the Preparation of 10h, 10o-q):
A solution of alkyne 9 in toluene and conc. sulfuric acid
(VPhMe/VH2SO4 =1:4, 0.5 M) was heated to 80 for four hours
until the reaction was complete as indicated by TLC. After
cooled down to r.t., the reaction mixture was basified to pH
3-(Phenylethynyl)quinoline (9b).
Following General
Procedure I, using 3-bromoquinoline (2.08 g, 10.0 mmol),
phenylacetylene (1.23 g, 12.0 mmol), the title compound was
obtained (1.66 g, 72% yield) as a yellow solid. The
spectroscopic data are consistent with material from

5
ACCEPTED MANUSCRIPT
commercial sources. 1H NMR (400 MHz, d6-DMSO) δ 9.01 (s,
1H), 8.63 (s, 1H), 8.01-8.06 (m, 2H), 7.82 (t, J = 6.8 Hz, 1H),
7.65-7.69 (m, 3H), 7.47 (s, 3H). 13C NMR (100 MHz, d6-
DMSO) δ 151.6, 146.3, 138.4, 131.5, 130.6, 129.3, 128.9,
128.8, 128.1, 127.6, 126.9, 121.8, 116.4, 92.3, 86.8.
(100 MHz, CDCl3) δ 197.2, 150.1, 148.4, 138.1, 137.0, 136.3,
135.1, 133.5, 129.2, 129.0, 128.9, 128.8, 127.7, 123.5, 56.8.
HRMS (+ESI-TOF) m/z: [M + H]+ calcd for C19H16NO
274.1226; found 274.1222.
methyl 5-(2-oxo-2-phenylethyl)nicotinate (10h). Following
General Procedure Ⅱ, using 9a (2.0 g, 8.43 mmol), compound
3-(phenylethynyl)-4-(trifluoromethyl)pyridine
Following General Procedure using 3-bromo-4-
(trifluoromethyl)pyridine (2.3g, 10.18 mmol) and
(9c).
1
,
10h was obtained (541 mg, 25% yield) as a yellow oil. H
NMR (400 MHz, CDCl3) δ 9.14 (d, J = 1.6 Hz, 1H), 8.68 (d, J
= 2.0 Hz, 1H), 8.22 (d, J = 2.0 Hz, 1H), 8.02-8.04 (m, 2H),
7.60-7.70 (m, 1H), 7.44-7.55 (m, 2H), 4.38 (s, 2H), 3.95 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 195.9, 165.8, 154.6, 149.6,
138.5, 136.3, 133.9, 130.2, 129.0, 128.5, 126.0, 52.6, 42.1.
HRMS (+ESI-TOF) m/z: [M + Na] + calcd for C15H13NO3Na
278.0788, found 278.0784.
phenylacetylene (1.25 g, 12.2 mmol), compound 9c was
obtained (1.75 g, 70% yield) as a yellow solid. 1H NMR (400
MHz, CDCl3) δ 8.93 (s, 1H), 8.69 (d, J = 4.4 Hz, 1H), 7.55-
7.59 (m, 3H), 7.39-7.40 (m, 3H). 13C NMR (100 MHz, CDCl3)
δ 154.3, 149.0, 132.0, 129.6, 128.6, 123.8, 122.1, 121.1, 119.4
(q, J = 4.0 Hz), 117.7, 98.4, 82.3. HRMS (+ESI-TOF) m/z: [M
+ H] + calcd for C14H9NF3 248.0682, found 248.0664.
1-phenyl-2-(5-phenylpyridin-3-yl)ethan-1-one (10i). In a
sealed tube equipped with magnetic stir bar was combined
Pd(OAc)2 (67 mg, 0.3 mmol), P(tBu)3·HBF4 (35 mg, 0.12
mmol), t-BuONa (1.44 g, 14.95 mmol) and degassed
anhydrous THF (31 ml). After stirring for 5 min under argon,
3-bromo-5-phenylpyridine (1.40 g, 5.98 mmol) and
acetophenone (1.08 g, 8.97 mmol) were added. The resulting
mixture was heated to reflux for 15 hours. After cooled down
to r.t., the mixture was diluted with DCM and water, filtered
through Celite, and the filtrate was separated. Water phase was
extracted with DCM. The combined organic phase was dried,
concentrated in vacuo to give the crude product, which was
chromatographed gradiently on silica gel with PE/EA
(30:1~10:1) to afford 10i (750 mg, 46% yield) as a yellow oil.
1H NMR (400 MHz, CDCl3) δ 8.76 (d, J = 2.0 Hz, 1H), 8.51
(d, J = 2.0 Hz, 1H), 8.05 (d, J = 7.2 Hz, 2H), 7.80 (s, 1H),
7.63-7.57 (m, 3H), 7.52-7.45 (m, 4H), 7.40 (d, J = 7.2 Hz, 1H),
4.37 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 196.5, 149.4,
147.1, 137.8, 136.6, 136.4, 135.8, 133.7, 130.2, 129.2, 129.0,
128.6, 128.3, 127.4, 42.4. HRMS (+ESI-TOF) m/z: [M + H] +
calcd for C19H16NO 274.1226; found 274.1217.
1-(pyridin-3-yl)propan-2-one (10a). This compound was
obtained from commercial sources.
1-(quinolin-3-yl)propan-2-one (10b). This compound was
obtained from commercial sources.
1-(pyridin-3-yl)butan-2-one (10c). This compound was
obtained from commercial sources.
1-phenyl-2-(pyridin-3-yl)ethan-1-one (10d). This compound
was obtained from commercial sources.
3-(pyridin-3-yl)butan-2-one (10e). To an ice cold suspension
of NaNH2 (0.79 g, 20.35 mmol) in anhydrous THF (40 ml)
was added a solution of 1-(pyridin-3-yl)propan-2-one (2.5 g,
18.50 mmol) in THF (46 ml) slowly under argon. After stirring
for 1.5 hours at 0 , a solution of iodomethane (3.15 g, 22.19
mmol) in THF (4 ml) was added. The resulting reaction
mixture was warmed to r.t. and stirred for several hours until
the reaction was complete as indicated by TLC. The reaction
was quenched by water, and the water phase was extracted
with EA for three times. The combined organic phase was
washed with brine, dried over Na2SO4, concentrated in vacuo
and chromatographed gradiently on silica gel with PE/EA
(20:1~10:1) to give 10e (1.49 g, 54% yield) as a yellow oil.
The spectroscopic data are consistent with data previously
reported.22 1H NMR (400 MHz, CDCl3) δ 8.53 (s, 2H), 7.54 (d,
J = 8.0 Hz, 1H), 7.29 (t, J = 3.6 Hz, 1H), 3.80 (q, J = 7.2 Hz,
1H), 2.10 (s, 3H), 1.43 (d, J = 7.2 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 207.8, 149.7, 148.9, 136.1, 135.0, 123.9, 51.0,
28.7, 17.4.
1-(6-chloropyridin-3-yl)propan-2-one (10j). This compound
was obtained from commercial sources.
1-(6-chloropyridin-3-yl)butan-2-one (10k). To a solution of
2-(6-chloropyridin-3-yl)-N-methoxy-N-methylacetamide (2 g,
9.3 mmol) in dry tetrahydrofuran (20 ml) at 0 °C was added
ethylmagnesium bromide (1.36 g, 10.2 mmol) and stirred for 1
h at r.t. The reaction mixture was quenched with aqueous
ammonium chloride solution and then extracted thrice with
ethyl acetate. The combined organic layer was dried over
Na2SO4, filtered, concentrated, and purified by flash column
chromatography using PE/EA (10:1~3:1) as eluent. The title
compound was obtained (776 mg, 45% yield) as a yellow oil.
1H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 2.4 Hz, 1H), 7.51
(dd, J = 8.0, 2.4 Hz, 1H), 7.29 (d, J = 8.4 Hz, 1H), 3.69 (s, 2H),
2.54 (q, J = 7.2 Hz, 2H), 1.08 (t, J = 7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 207.0, 150.4, 150.3, 140.0, 128.9, 124.2,
45.4, 36.1, 7.8. HRMS(+ESI-TOF) m/z: [M + H]+ calcd for
C9H11ClNO 184.0524, found 184.0517.
2-(pyridin-3-yl)cyclohexan-1-one (10f). This compound was
obtained from commercial sources.
1,2-diphenyl-2-(pyridin-3-yl)ethan-1-one
(10g).
This
compound was prepared following a known procedure23 with
slightly modification. To a suspension of PdCl2(DtBPF) (223
mg, 5mol%), t-BuONa (987 mg, 10.27 mmol) in degassed
anhydrous toluene (27 ml) was added 1-phenyl-2-(pyridin-3-
yl)ethan-1-one（1.35 g, 6.85 mmol）and iodobenzene (1.54 g,
7.54 mmol) under argon. The resulting mixture was heated to
reflux for 16 hurs. After cooled down to r.t., the mixture was
diluted with EA, filtered through Celite, and the filtrate was
concentrated in vacuo, which was chromatographed gradiently
on silica gel with PE/EA (15:1~5:1) to afford 10g (1.08 g,
58% yield) as a brown oil. 1H NMR (400 MHz, CDCl3) δ 8.51
(d, J = 2.0 Hz, 1H), 8.46 – 8.45 (m, 1H), 7.99 (d, J = 7.6 Hz,
2H), 7.61 (d, J = 8.0 Hz, 1H), 7.51 (t, J = 7.2 Hz, 1H), 7.40 (t,
J = 8..0 Hz, 2H), 7.35 – 7.21 (m, 6H), 6.03 (s, 1H); 13C NMR
2-(5-methylpyridin-3-yl)-1-phenylethan-1-one (10l). This
compound was obtained from commercial sources.
2-(4-methylpyridin-3-yl)-1-phenylethan-1-one
(10m).
Following the procedure for 10i, using 3-bromo-4-
methylpyridine (2 g, 11.627 mmol), the title compound was
obtained (646 mg, 26%) as a black solid. The spectroscopic
1
data are consistent with material from commercial sources. H

6
Tetrahedron
ACCEPTED MANUSCRIPT
NMR (400 MHz, CDCl3) δ 8.41 (d, J = 4.8 Hz, 1H), 8.34 (s,
1H), 8.03-8.06 (m, 2H), 7.60-7.63 (m, 1H), 7.49-7.53 (m, 2H),
7.14 (d, J = 4.8 Hz, 1H), 4.34 (s, 2H), 2.24 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 196.2, 150.9, 148.5, 146.9, 136.5, 133.7,
129.8, 128.9, 128.4, 125.4, 40.7, 19.4. HRMS (+ESI-TOF)
m/z: [M + H] + calcd for C14H14NO 212.1070, found 212.1066.
127.9, 125.8, 46.7, 30.0. HRMS (+ESI-TOF) m/z: [M + H] +
calcd for C8H10NO2 152.0706, found 152.0709.
3-(2-oxopropyl)quinoline 1-oxide (1b). Following General
Procedure , using 10b (444 mg, 2.397 mmol), compound 1b
1
was obtained (367 mg, 76% yield) as a yellow solid. H NMR
(400 MHz, CDCl3) δ 8.71 (d, J = 8.8 Hz, 1H), 8.44 (s, 1H),
7.83 (d, J = 8.0 Hz, 1H), 7.74 (t, J = 7.2 Hz, 1H), 7.64 (t, J =
7.6 Hz, 1H), 7.58 (s, 1H), 3.83 (s, 2H), 2.29 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 203.6, 140.6, 137.0, 130.4, 130.2, 129.2,
128.0, 127.9, 126.6, 119.8, 47.4, 30.0. HRMS (+ESI-TOF)
m/z: [M + H] + calcd for C12H12NO2 202.0863, found 202.0856.
1-(6-methylpyridin-3-yl)propan-2-one
(10n).
This
compound was obtained from commercial sources.
2-(6-methylpyridin-3-yl)-1-phenylethan-1-one
(10o).
Following Following General Procedure , using 2-methyl-5-
(phenylethynyl)pyridine (2.30 g, 11.9 mmol), the title
compound was obtained (880 mg, 35% yield) as a yellow oil.
The spectroscopic data are consistent with material from
3-(2-oxobutyl)pyridine 1-oxide (1c). Following General
Procedure , using 1-(pyridin-3-yl)butan-2-one (430 mg, 2.88
mmol), compound 1c was obtained (343 mg, 72% yield) as a
yellow oil. 1H NMR (400 MHz, CD3OD) δ 8.25 (s, 2H), 7.51 –
7.45 (m, 2H), 3.92 (s, 2H), 2.63 (q, J = 7.2 Hz, 2H), 1.06 (t, J
= 7.2 Hz, 3H); 13C NMR (100 MHz, CD3OD) δ 208.3, 141.2,
138.6, 136.8, 132.9, 127.4, 45.5, 36.6, 7.9. HRMS (+ESI-
TOF) m/z: [M + Na]+ calcd for C9H11NO2Na 188.0682; found
188.0677.
1
commercial sources. H NMR (400 MHz, CDCl3) δ 8.40 (d, J
= 2.0 Hz, 1H), 8.02-7.99 (m, 1H), 7.60-7.56 (m, 1H), 7.50-
7.45 (m, 3H), 7.13 (d, J = 8.0 Hz, 1H), 4.26 (s, 2H), 2.54 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 196.8, 157.1, 149.9, 137.6,
136.4, 133.5, 128.9, 128.5, 127.1, 123.2, 42.1, 24.1. HRMS
+
(+ESI-TOF) m/z: [M + H] calcd for C14H14NO 212.1070,
found 212.1078.
1-phenyl-2-(quinolin-3-yl)ethan-1-one (10p). Following
General Procedure , using 9b (1.0 g, 4.36 mmol), compound
10p was obtained (450 mg, 42% yield) as a yellow solid. The
spectroscopic data are consistent with material from
commercial sources. 1H NMR (400 MHz, d6-DMSO) δ 8.83 (d,
J = 2.0 Hz, 1H), 8.21 (d, J = 1.6 Hz, 1H), 8.11-8.13 (m, 2H),
8.02 (d, J = 8.4 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.71-7.76
(m, 1H), 7.68 (t, J = 7.2 Hz, 1H), 7.56-7.62 (m, 3H), 4.70 (s,
2H). 13C NMR (100 MHz, d6-DMSO) δ 197.3, 152.7, 146.4,
136.3, 136.1, 133.5, 129.0, 128.8, 128.7, 128.5, 128.3, 127.7,
127.6, 126.6, 42.0. HRMS (+ESI-TOF) m/z: [M + H] + calcd
for C17H14NO 248.1070, found 248.1072.
3-(2-oxo-2-phenylethyl)pyridine 1-oxide (1d). Following
General Procedure , using 10d (600 mg, 3.042 mmol),
compound 1d was obtained (465 mg, 72% yield) as a yellow
1
solid. H NMR (400 MHz, d6-DMSO) δ 8.19 (s, 1H), 8.13 (d,
J = 6.4 Hz, 1H), 8.04-8.06 (m, 2H), 7.69 (t, J = 7.6 Hz, 1H),
7.57 (t, J = 8.0 Hz, 2H), 7.38 (t, J = 8.0 Hz, 1H), 7.24 (d, J =
8.0 Hz, 1H), 4.49 (s, 2H). 13C NMR (100 MHz, d6-DMSO) δ
196.2, 139.7, 136.9, 136.1, 134.7, 133.6, 128.8, 128.2, 127.3,
-
125.8, 41.3. HRMS (-ESI-TOF) m/z: [M - H] calcd for
C13H10NO2 212.0717, found 212.0719.
3-(3-oxobutan-2-yl)pyridine 1-oxide (1e). Following General
Procedure , using 10e (1.49 g, 10 mmol), the title compound
1
1-phenyl-2-(4-(trifluoromethyl)pyridin-3-yl)ethan-1-one
(10q). Following General Procedure , using 9c (1.75 g, 7.079
mmol), compound 10q was obtained (1.7 g, 91% yield) as a
yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.73 (d, J = 4.8 Hz,
1H), 8.62 (s, 1H), 8.03 (d, J = 7.6 Hz, 2H), 7.63 (t, J = 7.2 Hz,
1H), 7.56 (d, J = 5.2 Hz, 1H), 7.52 (t, J = 7.6 Hz, 2H), 4.52 (s,
2H). 13C NMR (100 MHz, CDCl3) δ 195.2, 154.1, 149.5, 136.9
(q, J = 32.0 Hz), 136.2, 133.9, 129.0, 128.3, 127.7, 124.6 (q, J
1e was obtained (1.38 g, 86% yield) as a yellow oil. H NMR
(400 MHz, CDCl3) δ 8.22 (s, 1H), 8.18 (d, J = 6.0 Hz, 1H),
7.30 (d, J = 6.0 Hz, 1H), 7.18 (d, J = 7.6 Hz, 1H), 3.75 (q, J =
6.8 Hz, 1H), 2.17 (s, 3H), 1.45 (d, J = 6.8 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 206.2, 139.8, 139.1, 138.1, 126.1, 125.9,
50.5, 28.7, 17.2. HRMS (+ESI-TOF) m/z: [M + H]+ calcd for
C9H12NO2 166.0836; found 166.0859.
3-(2-oxocyclohexyl)pyridine 1-oxide (1f). Following General
Procedure , using 2-(pyridin-3-yl)cyclohexan-1-one (500 mg,
2.85 mmol), the title compound was obtained (360 mg, 66%
yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.13 (d,
J = 6.4 Hz, 1H), 8.04 (s, 1H), 7.25 (t, J = 8.0 Hz, 1H), 7.08 (d,
J = 8.0 Hz, 1H), 3.57 (dd, J = 12.0, 5.2 Hz, 1H), 2.46-2.60 (m,
2H), 2.29-2.34 (m, 1H), 2.19-2.23 (m, 1H), 2.05-2.06 (m, 1H),
1.79-2.04 (m, 3H). 13C NMR (100 MHz, CDCl3) δ 207.7,
139.5, 138.2, 137.7, 127.1, 125.5, 54.6, 42.2, 35.0, 27.7, 25.4.
HRMS (+ESI-TOF) m/z: [M + Na] + calcd for C11H13NO2Na
214.0839, found 214.0832.
= 273.0 Hz), 119.7 (q, J = 4.0 Hz), 40.0. HRMS (+ESI-TOF)
+
m/z: [M + H]
calcd for C14H11NOF3 266.0787, found
266.0777.
2-(4-methoxypyridin-3-yl)-1-phenylethan-1-one
(10r).
Following the procedure for 10i, using 3-bromo-4-
methoxypyridine (4 g, 21.27 mmol), the title compound was
1
obtained (1.45 g, 30%) as a yellow oil. H NMR (400 MHz,
CDCl3) δ 8.47 (d, J = 5.6 Hz, 1H), 8.31 (s, 1H), 8.03 (d, J =
7.6 Hz, 2H), 7.59 (t, J = 7.2 Hz, 1H), 7.49 (t, J = 7.2 Hz, 2H),
6.83 (d, J = 5.6 Hz, 1H), 4.27 (s, 2H), 3.82 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 196.3, 164.1, 151.4, 150.7, 136.7, 133.4,
128.8, 128.4, 120.1, 106.3, 55.5, 37.6. HRMS (+ESI-TOF)
m/z: [M + H] + calcd for C14H14NO2 228.1019, found 228.1016.
3-(2-oxo-1,2-diphenylethyl)pyridine 1-oxide (1g). Following
General Procedure , using 10g (1.5 g, 5.49 mmol) and m-
CPBA (1.23 g, 6.04 mmol, 85%), the title compound was
1
3-(2-oxopropyl)pyridine 1-oxide (1a). Following General
Procedure , using 10a (2 g, 14.8 mmol), compound 1a was
obtained (947 mg, 60% yield) as a yellow oil. H NMR (400
MHz, CDCl3) δ 8.02 – 8.00 (m, 2H), 7.88 (d, J = 8.0 Hz, 2H),
7.45 (t, J = 7.6 Hz, 1H), 7.33 (t, J = 8.0 Hz, 2H), 7.28 (t, J =
8.0 Hz, 2H), 7.22 – 7.19 (m, 3H), 7.12 (d, J = 4.0 Hz, 2H),
5.88 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 196.0, 140.1,
139.1, 137.7, 136.4, 135.8, 133.7, 129.6, 129.0, 128.9, 128.8,
1
obtained (1.97 g, 88% yield) as a yellow solid. H NMR (400
MHz, CDCl3) δ 8.16 (d, J = 6.4 Hz, 1H), 8.12 (s, 1H), 7.29 (d,
J = 8.0 Hz, 1H), 7.15-7.16 (m, 1H), 3.73 (s, 2H), 2.28 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 203.0, 140.0, 137.9, 133.5,

7
ACCEPTED MANUSCRIPT
128.2, 127.3, 125.4, 56.4. HRMS (+ESI-TOF) m/z: [M + H]+
calcd for C19H16NO2 290.1176; found 290.1170.
solid. 1H NMR (400 MHz, CDCl3) δ 8.15 (s, 1H), 7.23 (d, J =
8.0 Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H), 3.66 (s, 2H), 2.51 (s,
3H), 2.24 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 203.6, 147.7,
139.8, 130.7, 127.5, 126.3, 46.5, 29.9, 17.5. HRMS (+ESI-
TOF) m/z: [M + H] calcd for C9H12NO2 166.0863; found
166.0871.
3-(methoxycarbonyl)-5-(2-oxo-2-phenylethyl)pyridine
1-
oxide (1h). Following General Procedure , using 10h (480
mg, 1.880 mmol), compound 1h was obtained (252 mg, 49%
yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.70 (s,
1H), 8.29 (s, 1H), 7.99-8.01 (m, 2H), 7.78 (s, 1H), 7.64 (t, J =
7.6 Hz, 1H), 7.53 (t, J = 7.6 Hz, 2H), 4.32 (s, 2H), 3.96 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 195.9, 165.8, 154.6, 149.6,
138.5, 136.3, 133.9, 130.2, 129.0, 128.5, 126.0, 52.6, 42.1.
+
2-methyl-5-(2-oxo-2-phenylethyl)pyridine 1-oxide (1o).
Following General Procedure , using 10o (400 mg, 1.893
mmol), the title compound was obtained (360 mg, 84% yield)
1
as a white solid. H NMR (400 MHz, CDCl3) δ 8.22 (s, 1H),
+
HRMS (+ESI-TOF) m/z: [M + H] calcd for C15H14NO4
8.00 (s, 1H), 7.98 (t, J = 1.6 Hz , 1H), 7.63-7.59 (m, 1H), 7.52-
7.48 (m, 2H), 7.23 (d, J = 8.0 Hz, 1H), 7.11 (dd, J = 8.0 Hz,
1.2 Hz, 1H), 4.22 (s, 2H), 2.51 (d, J = 7.6 Hz, 3H). 13C NMR
(100 MHz, CDCl3) δ 195.4, 147.6, 140.1, 136.0, 133.9, 131.2,
129.0, 128.5, 127.4, 126.2, 41.7, 17.6. HRMS (+ESI-TOF)
272.0917, found 272.0911.
3-(2-oxo-2-phenylethyl)-5-phenylpyridine 1-oxide (1i).
Following General Procedure , using 10i (370 mg, 1.463
mmol), the title compound was obtained (360 mg, 92% yield)
+
m/z: [M + Na] calcd for C14H13NO2Na 250.0839; found
1
as a white solid. H NMR (400 MHz, CDCl3) δ 8.39 (s, 1H),
250.0830.
8.16 (s, 1H), 8.03-8.00 (m, 2H), 7.65-7.61 (m, 1H), 7.54-7.40
(m, 8H), 4.32 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 195.0,
140.0, 138.4, 136.2, 135.9, 135.1, 134.1, 133.7, 129.5, 129.4,
129.1, 128.5, 127.1, 126.9, 41.9. HRMS (+ESI-TOF) m/z: [M
+ H] + calcd for C19H16NO2 290.1176; found 290.1165.
3-(2-oxo-2-phenylethyl)quinoline 1-oxide (1p). Following
General Procedure , using 10p (450 mg, 1.820 mmol),
compound 1p was obtained (400 mg, 84% yield) as a yellow
solid. 1H NMR (400 MHz, CDCl3) δ 8.72 (d, J = 8.8 Hz, 1H),
8.54 (s, 1H), 8.04 (d, J = 7.6 Hz, 2H), 7.83 (d, J = 8.4 Hz, 1H),
7.74 (t, J = 8.0 Hz, 1H), 7.61-7.67 (m, 3H), 7.52 (t, J = 7.6 Hz,
2H), 4.40 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 195.5, 140.5,
137.3, 136.1, 134.0, 130.4, 130.3, 129.12, 129.10, 128.6, 128.4,
128.1, 127.0, 119.8, 42.4. HRMS (+ESI-TOF) m/z: [M + H] +
calcd for C17H14NO2 264.1019, found 264.1010.
2-chloro-5-(2-oxopropyl)pyridine 1-oxide (1j). Following
General Procedure , using 10j (400 mg, 2.36 mmol), the title
compound was obtained (320 mg, 73% yield) as a white solid.
1H NMR (400 MHz, CDCl3) δ 8.21 (s, 1H), 7.45 (d, J = 8.4 Hz,
1H), 7.05 (d, J = 8.0 Hz, 1H), 3.70 (s, 2H), 2.28 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 202.8, 141.1, 140.7, 131.3, 127.5,
126.7, 46.2, 30.1. HRMS (-ESI-TOF) m/z: [M - H]- calcd for
C8H7NO2Cl 184.0171; found 184.0180.
3-(2-oxo-2-phenylethyl)-4-(trifluoromethyl)pyridine
1-
oxide (1q). Following General Procedure , using 10q (1.7 g,
6.413 mmol), compound 1q was obtained (1.0g, 55% yield) as
2-chloro-5-(2-oxobutyl)pyridine 1-oxide (1k). Following
General Procedure , using 10k (1.1 g, 6.0 mmol), the title
compound was obtained (410 mg, 34% yield) as a yellow solid.
1H NMR (400 MHz, CDCl3) δ 8.21 (s, 1H), 7.43 (d, J = 8.4 Hz,
1H), 7.06 (d, J = 8.0 Hz, 1H), 3.65 (s, 2H), 2.55 (q, J = 7.2 Hz,
2H), 1.09 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
205.6, 141.1, 140.6, 131.6, 127.6, 126.7, 45.0, 36.3, 7.8.
HRMS(+ESI-TOF) m/z: [M + Na]+ calcd for C9H10ClNO2Na
222.0292, found 222.0285.
1
a yellow solid. H NMR (400 MHz, CDCl3) δ 8.16-8.20 (m,
2H), 7.99 (d, J = 7.6 Hz, 2H), 7.64 (t, J = 7.2 Hz, 1H), 7.51-
7.54 (m, 3H), 4.43 (s, 2H). 13C NMR (100 MHz, CDCl3) δ
193.8, 142.5, 138.0, 135.7, 134.1, 132.4, 129.0, 128.3, 125.9
(q, J = 32.0 Hz), 123.3 (q, J = 5.0 Hz), 122.8 (q, J = 271.0 Hz),
+
39.6. HRMS (+ESI-TOF) m/z: [M + Na]
C14H10NO2F3Na 304.0556, found 304.0544.
calcd for
4-methoxy-3-(2-oxo-2-phenylethyl)pyridine 1-oxide 1-oxide
(1r). Following General Procedure , using 10r (640 mg, 2.82
mmol), compound 1r was obtained (300 mg, 44% yield) as a
3-methyl-5-(2-oxo-2-phenylethyl)pyridine 1-oxide (1l).
Following General Procedure , using 10l (400 mg, 1.893
mmol), compound 1l was obtained (356 mg, 83% yield) as a
1
yellow solid. H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 6.8
Hz, 1H), 8.09 (s, 1H), 8.01 (d, J = 8.0 Hz, 2H), 7.60 (t, J = 7.2
Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 6.80 (d, J = 6.8 Hz, 1H),
4.23 (s, 2H), 3.83 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
194.6, 157.0, 141.2, 139.1, 136.2, 133.8, 128.9, 128.4, 123.3,
107.7, 56.5, 37.3. HRMS (+ESI-TOF) m/z: [M + H] + calcd for
C14H14NO3 244.0968, found 244.0953.
1
yellow solid. H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 5.2
Hz, 2H), 7.98-8.00 (m, 2H), 7.61-7.65 (m, 1H), 7.49-7.53 (m,
2H), 7.06 (s, 1H), 4.22 (s, 2H), 2.31 (s, 3H). 13C NMR (100
MHz, CDCl3) δ 195.0, 137.8, 137.3, 136.4, 135.9, 133.9, 133.1,
129.4, 129.0, 128.4, 41.7, 18.3. HRMS (+ESI-TOF) m/z: [M +
Na] + calcd for C14H13NO2Na 250.0839, found 250.0835.
1-benzyl-2-methyl-1H-pyrrolo[2,3-b]pyridine
Following General Procedure , using 1a (120 mg, 0.794
mmol) and benzylamine (128 mg, 1.191 mmol), compound 3a
(3a).
4-methyl-3-(2-oxo-2-phenylethyl)pyridine 1-oxide (1m).
Following General Procedure , using 10m (600 mg, 2.840
mmol), compound 1m was obtained (469 mg, 73% yield) as a
yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.09-8.11 (m, 2H),
8.01-8.03 (m, 2H), 7.63-7.67 (m, 1H), 7.51-7.55 (m, 2H), 7.14
(d, J = 6.4 Hz, 1H), 4.28 (s, 2H), 2.23 (s, 3H). 13C NMR (100
MHz, CDCl3) δ 194.6, 140.0, 138.4, 137.5, 136.0, 134.1, 133.1,
129.1, 128.4, 127.4, 40.6, 18.6. HRMS (+ESI-TOF) m/z: [M +
Na] + calcd for C14H13NO2Na 250.0839, found 250.0827.
1
was obtained (99 mg, 56% yield) as a white solid. H NMR
(400 MHz, d6-DMSO) δ 8.16 (d, J = 4.8 Hz, 1H), 7.87 (d, J =
7.6 Hz, 1H), 7.26-7.30 (m, 2H), 7.20-7.23 (m, 1H), 7.05 (d, J
= 7.2 Hz, 3H), 6.30 (s, 1H), 5.50 (s, 2H), 2.34 (s, 3H). 13C
NMR (100 MHz, d6-DMSO) δ 148.1, 141.2, 138.4, 137.7,
128.6, 127.1, 127.0, 126.4, 120.0, 115.8, 98.0, 44.0, 12.7. The
spectroscopic data are consistent with data previously
reported.20
2-methyl-5-(2-oxopropyl)pyridine 1-oxide (1n). Following
General Procedure , using 10n (420 mg, 2.815 mmol), the
title compound was obtained (360 mg, 77% yield) as a white
2-methyl-1H-pyrrolo[2,3-b]pyridine
(3b).
Following
General Procedure , using 1a (120 mg, 0.79 mmol) and

8
Tetrahedron
ACCEPTED MANUSCRIPT
ammonia (0.4 M in 1,4-dioxane) (3 ml, 1.2 mmol), compound
3b was obtained (38 mg, 36% yield) as a yellow solid. The
spectroscopic data are consistent with material from
127.2, 120.2, 116.5, 99.2, 13.5. HRMS (+ESI-TOF) m/z: [M +
Na] + calcd for C14H12N2Na 231.0893, found 231.0883.
1-(4-methoxybenzyl)-2-methyl-1H-pyrrolo[2,3-b]pyridine
(3h). Following General Procedure , using 1a (120 mg,
0.794 mmol) and 4-methoxybenzylamine (163 mg, 1.191
mmol), compound 3h was obtained (76 mg, 38% yield) as a
1
commercial sources. H NMR (400 MHz, CDCl3) δ 10.32 (s,
1H), 8.20 (dd, J = 4.8 Hz, 1.2 Hz, 1H), 7.82 (dd, J = 7.6 Hz,
1.2 Hz, 1H), 7.04 (dd, J = 8.0 Hz, 5.2 Hz, 1H), 6.18 (s, 1H),
2.53 (d, J = 0.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 149.1,
140.3, 137.0, 127.8, 122.3, 115.6, 98.2, 14.2.
1
white solid. H NMR (400 MHz, d6-DMSO) δ 8.17 (dd, J =
4.8 Hz, 1.6 Hz, 1H), 7.85 (dd, J = 8.0 Hz, 1.6 Hz, 1H), 7.02-
7.07 (m, 3H), 6.83-6.85 (m, 2H), 6.27 (d, J = 0.8 Hz, 1H), 5.42
(s, 2H), 3.69 (s, 3H), 2.35 (d, J = 0.8 Hz, 3H). 13C NMR (100
MHz, d6-DMSO) δ 158.3, 148.0, 141.2, 137.6, 130.3, 127.9,
127.0, 120.0, 115.7, 114.0, 98.0, 55.0, 43.5, 12.8. HRMS
1-ethyl-2-methyl-1H-pyrrolo[2,3-b]pyridine (3c). Following
General Procedure , using 1a (120 mg, 0.794 mmol) and
ethylamine (2.0 M in THF) (0.6 ml, 1.191 mmol), compound
1
3c was obtained (64 mg, 50% yield) as a yellow solid. H
+
NMR (400 MHz, CDCl3) δ 8.35 (d, J = 5.2 Hz, 1H), 8.31 (d, J
= 7.6 Hz, 1H), 7.41 (t, J = 6.4 Hz, 1H), 6.56 (s, 1H), 4.76 (q, J
= 6.8 Hz, 2H), 2.58 (s, 3H), 1.54 (t, J = 6.8 Hz, 3H). 13C NMR
(100 MHz, CDCl3) δ 142.0, 138.5, 135.3, 131.5, 126.0, 115.2,
101.6, 40.7, 15.7, 13.1. HRMS (+ESI-TOF) m/z: [M + H] +
calcd for C10H13N2 161.1073, found 161.1073.
(+ESI-TOF) m/z: [M + H] calcd for C16H17N2O 253.1335,
found 253.1334.
1-(4-methoxyphenyl)-2-methyl-1H-pyrrolo[2,3-b]pyridine
(3i). Following General Procedure , using 1a (120 mg, 0.794
mmol) and p-anisidine (147 mg, 1.191 mmol), compound 3i
1
was obtained (94 mg, 50% yield) as a white solid. H NMR
1-butyl-2-methyl-1H-pyrrolo[2,3-b]pyridine (3d). Following
General Procedure , using 1a (120 mg, 0.794 mmol) and
butylamine (87 mg, 1.191 mmol), compound 3d was obtained
(400 MHz, d6-DMSO) δ 8.07 (dd, J = 4.8 Hz, 1.6 Hz, 1H),
7.89 (dd, J = 7.6 Hz, 1.6 Hz, 1H), 7.32-7.36 (m, 2H), 7.06-
7.12 (m, 3H), 6.41 (d, J = 0.8 Hz, 1H), 3.84 (s, 3H), 2.28 (s,
3H). 13C NMR (100 MHz, d6-DMSO) δ 158.6, 149.0, 141.6,
138.0, 129.4, 128.8, 127.1, 120.1, 116.3, 114.3, 98.7, 55.4,
13.4. HRMS (+ESI-TOF) m/z: [M + H] + calcd for C15H15N2O
239.1179, found 239.1190.
1
(80 mg, 54% yield) as a colorless oil. H NMR (400 MHz, d6-
DMSO) δ 8.13 (d, J = 4.8 Hz, 1H), 7.80 (dd, J = 7.6 Hz, 1.2
Hz, 1H), 7.00 (dd, J = 7.6 Hz, 4.8 Hz, 1H), 6.22 (s, 1H), 4.21 (t,
J = 7.2 Hz, 2H), 2.45 (s, 3H), 1.63-1.70 (m, 2H), 1.25-1.34 (m,
2H) , 0.90 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, d6-DMSO)
δ 147.8, 140.9, 137.5, 126.7, 119.9, 115.4, 97.5, 40.8, 31.9,
19.6, 13.7, 12.7. HRMS (+ESI-TOF) m/z: [M + H] + calcd for
C12H17N2 189.1386, found 189.1376.
1-cyclohexyl-2-methyl-1H-pyrrolo[2,3-b]pyridine
(3j).
Following General Procedure , using 1a (120 mg, 0.794
mmol) and cyclohexylamine (118 mg, 1.19 mmol), compound
1
3j was obtained (60 mg, 35% yield) as a white solid. H NMR
1-allyl-2-methyl-1H-pyrrolo[2,3-b]pyridine (3e). Following
General Procedure , using 1a (120 mg, 0.794 mmol) and
allylamine (111 mg, 1.191 mmol), compound 3e was obtained
(400 MHz, CDCl3) δ 8.21 (dd, J = 4.8 Hz, 1.6 Hz, 1H), 7.74
(dd, J = 7.6 Hz, 1.6 Hz, 1H), 6.96 (dd, J = 8.0 Hz, 4.8 Hz, 1H),
6.15 (d, J = 0.8 Hz, 1H), 4.43-4.58 (m, 1H), 2.46-2.51 (m, 5H),
1.84-1.95 (m, 4H), 1.76 (d, J = 12.0 Hz, 1H), 1.25-1.54 (m,
3H). 13C NMR (100 MHz, CDCl3) δ 148.7, 141.0, 137.4, 126.9,
120.8, 115.4, 98.8, 55.1, 31.7, 26.6, 25.6, 15.0. HRMS (+ESI-
1
(53 mg, 39% yield) as a colorless oil. H NMR (400 MHz,
CDCl3) δ 8.23 (dd, J = 4.8 Hz, 1.6 Hz, 1H), 7.78 (dd, J = 8.0
Hz, 1.6 Hz, 1H), 7.01 (dd, J = 7.6 Hz, 4.8 Hz, 1H), 6.20 (d, J =
0.8 Hz, 1H), 5.95-6.05 (m, 1H), 5.08-5.12 (m, 1H), 4.89-4.91
(m, 2H), 4.75-4.81 (m, 1H), 4.43 (d, J = 0.4 Hz, 3H). 13C
NMR (100 MHz, CDCl3) δ 148.3, 141.7, 137.7, 134.0, 127.3,
120.7, 115.9, 115.8, 98.2, 43.7, 13.0. HRMS (+ESI-TOF) m/z:
[M + H] + calcd for C11H13N2 173.1073, found 173.1072.
+
TOF) m/z: [M + H] calcd for C14H19N2 215.1543, found
215.1533.
1,2-dimethyl-1H-pyrrolo[2,3-b]quinoline (3k). Following
General Procedure , using 1b (120 mg, 0.6 mmol) and
methylamine (2.0 M in THF) (0.6 ml, 1.2 mmol) in DCE at
reflux conditions, compound 3k was obtained (95 mg, 81%
1-isopropyl-2-methyl-1H-pyrrolo[2,3-b]pyridine
(3f).
1
Following General Procedure , using 1a (100 mg, 0.662
yield) as a yellow solid. H NMR (400 MHz, d6-DMSO) δ
mmol) and isopropylamine (59 mg, 0.993 mmol), compound
3f was obtained (40 mg, 35% yield) as a colorless oil. H
8.35 (s, 1H), 7.95-7.99 (m, 2H), 7.59 (t, J = 7.6 Hz, 1H), 7.38
1
(t, J = 7.6 Hz, 1H), 6.39 (s, 1H), 3.79 (s, 3H), 2.52 (s, 3H). 13
C
NMR (400 MHz, CDCl3) δ 8.21 (dd, J = 4.8 Hz, 1.6 Hz, 1H),
7.74 (dd, J = 7.6 Hz, 1.2 Hz, 1H), 6.97 (dd, J = 7.6 Hz, 4.8 Hz,
1H), 6.15 (d, J = 0.8 Hz, 1H), 5.03 (qui, J = 6.8 Hz, 1H), 2.51
(s, 3H), 1.66 (d, J = 6.8 Hz, 6H). 13C NMR (100 MHz, CDCl3)
δ 147.3, 139.9, 136.1, 125.7, 119.7, 114.2, 97.6, 45.2, 20.6,
13.5. HRMS (+ESI-TOF) m/z: [M + H] + calcd for C11H15N2
175.1230, found 175.1221.
NMR (100 MHz, d6-DMSO) δ 149.8, 143.5, 143.3, 128.1,
127.4, 127.0, 124.9, 124.4, 122.4, 121.9, 96.5, 27.7, 13.2.
+
HRMS (+ESI-TOF) m/z: [M + H] calcd for C13H13N2
197.1073; found 197.1071.
2-methyl-1H-pyrrolo[2,3-b]quinoline
(3l).
Following
General Procedure , using 1b (120 mg, 0.6 mmol) and
ammonia (0.4 M in 1,4-dioxane) (3 ml, 1.2 mmol), compound
1
2-methyl-1-phenyl-1H-pyrrolo[2,3-b]pyridine
(3g).
3l was obtained (42 mg, 38% yield) as a yellow solid. H
Following General Procedure , using 1a (120 mg, 0.794
mmol) and aniline (111 mg, 1.191 mmol), compound 3g was
obtained (85 mg, 53% yield) as a yellow oil. H NMR (400
MHz, d6-DMSO) δ 8.08 (dd, J = 4.8 Hz, 1.2 Hz, 1H), 7.91 (dd,
J = 8.0 Hz, 1.6 Hz, 1H), 7.57 (t, J = 7.2 Hz, 2H), 7.49 (d, J =
7.2 Hz, 1H), 7.43-7.45 (m, 2H), 7.09 (dd, J = 8.0 Hz, 4.8 Hz,
1H), 6.44 (s, 1H), 2.31 (s, 3H). 13C NMR (100 MHz, d6-
DMSO) δ 148.8, 141.7, 137.7, 136.2, 129.1, 128.2, 127.7,
NMR (400 MHz, d6-DMSO) δ 11.41 (s, 1H), 8.29 (s, 1H),
7.95 (d, J = 7.6 Hz, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.54-7.57
(m, 1H), 7.36 (t, J = 8.0 Hz, 1H), 6.28 (s, 1H), 2.47 (s, 3H).
13C NMR (100 MHz, d6-DMSO) δ 150.8, 143.8, 141.9, 128.0,
127.3, 126.7, 124.4, 122.9, 122.3, 97.0, 14.1. HRMS (+ESI-
1
+
TOF) m/z: [M + H] calcd for C12H11N2 183.0917; found
183.0919.

9
ACCEPTED MANUSCRIPT
2-methyl-1-phenyl-1H-pyrrolo[2,3-b]quinoline
(3m).
Following General Procedure , using 1b (120 mg, 0.6 mmol)
and aniline (111 mg, 1.2 mmol) in DCE at reflux conditions,
compound 3m was obtained (140 mg, 91% yield) as a yellow
1-benzyl-2,3-dimethyl-1H-pyrrolo[2,3-b]pyridine
(3r).
Following General Procedure IV, using 1e (120 mg, 0.727
mmol) and benzylamine (117 mg, 1.1 mmol), the title
compound was obtained (45 mg, 26% yield) as a white solid.
1H NMR (400 MHz, CDCl3) δ 8.24 (d, J = 4.4 Hz, 1H), 7.77
(d, J = 7.6 Hz, 1H), 7.25-7.18 (m, 3H), 7.04-7.00 (m, 3H),
5.50 (s, 2H), 2.25 (s, 3H), 2.24 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 148.2, 141.8, 138.6, 133.3, 128.7, 127.2, 126.6,
125.7, 121.2, 115.3, 105.4, 45.0, 10.5, 8.7. HRMS (+ESI-
1
solid. H NMR (400 MHz, d6-DMSO) δ 8.46 (s, 1H), 8.01 (d,
J = 8.4 Hz, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.51-7.64 (m, 6H),
7.41 (t, J = 7.6 Hz, 1H), 6.61 (s, 1H), 2.36 (s, 3H). 13C NMR
(100 MHz, d6-DMSO) δ 150.5, 143.9, 142.7, 136.3, 129.3,
128.6, 128.1, 127.9, 127.5, 127.3, 125.4, 124.9, 122.9, 121.9,
+
+
98.8, 14.1. HRMS (+ESI-TOF) m/z: [M + H] calcd for
TOF) m/z: [M + H] calcd for C16H17N2 237.1386; found
C18H15N2 259.1230; found 259.1231.
237.1380.
1-benzyl-2-methyl-1H-pyrrolo[2,3-b]quinoline
(3n).
9-benzyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-b]indole
(3s).
Following General Procedure , using 1b (120 mg, 0.6 mmol)
and benzylamine (128 mg, 1.192 mmol) in DCE at reflux
conditions, compound 3n was obtained (126 mg, 77% yield)
Following General Procedure , using 1f (120 mg, 0.628
mmol) and benzylamine (135 mg, 1.256 mmol) in DCE at
reflux conditions, compound 3s was obtained (71 mg, 43%
1
1
as a yellow solid. H NMR (400 MHz, d6-DMSO) δ 8.42 (s,
yield) as a yellow solid. H NMR (400 MHz, d6-DMSO) δ
1H), 8.01 (d, J = 8.0 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.59 (t,
J = 8.0 Hz, 1H), 7.40 (t, J = 8.0 Hz, 1H), 7.27-7.30 (m, 2H),
7.21-7.24 (m, 1H), 7.10 (d, J = 7.2 Hz, 2H), 6.48 (s, 1H), 5.61
(s, 2H), 2.42 (s, 3H). 13C NMR (100 MHz, d6-DMSO) δ 149.9,
143.7, 142.7, 138.4, 128.6, 128.1, 127.4, 127.1, 126.4, 125.3,
124.7, 122.6, 121.8, 97.6, 44.0, 13.2. The spectroscopic data
are consistent with data previously reported.24
8.15 (dd, J = 4.8 Hz, 1.6 Hz, 1H), 7.80 (dd, J = 7.6 Hz, 1.2 Hz,
1H), 7.21-7.29 (m, 3H), 7.08 (d, J = 7.2 Hz, 2H), 7.03 (dd, J =
8.0 Hz, 4.8 Hz, 1H), 5.41 (s, 2H), 2.61-2.63 (m, 4H), 1.75-1.82
(m, 4H). 13C NMR (100 MHz, d6-DMSO) δ 147.7, 141.3,
138.7, 136.2, 128.6, 127.1, 126.7, 125.4, 119.2, 115.2, 107.3,
43.9, 22.6, 22.4, 21.6, 20.4. The spectroscopic data are
consistent with data previously reported.15
2-methyl-1-(4-(methylsulfonyl)-2-(trifluoromethyl)benzyl)-
1-benzyl-2,3-diphenyl-1H-pyrrolo[2,3-b]pyridine
(3t).
1H-pyrrolo[2,3-b]quinoline (3o).
Procedure , using 1b (120 mg, 0.6 mmol) and (4-
Following General
Following General Procedure , using 1g (120 mg, 0.415
mmol) and benzylamine (67 mg, 0.623 mmol), compound 3t
was obtained (42 mg, 28% yield) as a yellow solid. H NMR
(400 MHz, d6-DMSO) δ 8.36 (d, J = 4.4 Hz, 1H), 8.09 (d, J =
8.0 Hz, 1H), 7.37-7.42 (m, 3H), 7.21-7.31 (m, 7H), 7.14-7.19
(m, 4H), 6.83 (d, J = 7.2 Hz, 2H), 5.47 (s, 2H). 13C NMR (100
MHz, d6-DMSO) δ 147.6, 143.4, 138.2, 137.4, 133.7, 130.8,
130.7, 129.2, 128.8, 128.6, 128.4, 128.3, 127.4, 127.0, 126.4,
126.0, 118.9, 117.0, 112.9, 45.1. HRMS (+ESI-TOF) m/z: [M
+ H] + calcd for C26H21N2 361.1699, found 361.1700.
1
(methylsulfonyl)-2-(trifluoromethyl)phenyl)methanamine (302
mg, 1.2 mmol) in DCE at reflux conditions, compound 3o was
obtained (173 mg, 69% yield) as a yellow solid. 1H NMR (400
MHz, d6-DMSO) δ 8.50 (s, 1H), 8.29 (s, 1H), 8.01-8.05 (m,
2H), 7.86 (d, J = 8.4 Hz, 1H), 7.58 (t, J = 8.0 Hz, 1H), 7.42 (t,
J = 7.6 Hz, 1H), 6.61-6.64 (m, 2H), 5.85 (s, 2H), 3.27 (s, 3H),
2.40 (s, 3H). 13C NMR (100 MHz, d6-DMSO) δ 149.7, 143.8,
142.6, 142.3, 140.3, 132.0, 128.3, 127.9, 127.5, 127.4, 126.7
(q, J = 31.0 Hz), 126.0, 125.2 (q, J = 5.0 Hz), 125.0, 123.0,
122.3, 121.9, 98.5, 43.3, 41.0, 12.8. HRMS (+ESI-TOF) m/z:
[M + H] + calcd for C21H18N2O2F3S 419.1036, found 419.1035.
methyl
1-benzyl-2-phenyl-1H-pyrrolo[2,3-b]pyridine-5-
carboxylate (3u). Following General Procedure , using 1h
(120 mg, 0.442 mmol) and benzylamine (95 mg, 0.884 mmol)
in DCE at reflux conditions, compound 3u was obtained (71
1-benzyl-2-ethyl-1H-pyrrolo[2,3-b]pyridine (3p). Following
General Procedure , using 1c (120 mg, 0.726 mmol) and
benzylamine (117 mg, 1.089 mmol), compound 3p was
1
mg, 47% yield) as a yellow solid. H NMR (400 MHz, d6-
DMSO) δ 8.86 (d, J = 2.0 Hz, 1H), 8.62 (d, J = 2.0 Hz, 1H),
7.45-7.53 (m, 5H), 7.16-7.21 (m, 3H), 6.82-6.85 (m, 3H), 5.63
(s, 2H), 3.90 (s, 3H). 13C NMR (100 MHz, d6-DMSO) δ 166.2,
150.5, 144.2, 143.1, 137.8, 131.2, 130.0, 128.94, 128.86,
128.81, 128.5, 127.1, 126.1, 119.4, 118.7, 101.7, 52.1, 45.5.
1
obtained (63 mg, 37% yield) as a white solid. H NMR (400
MHz, d6-DMSO) δ 8.19 (s, 1H), 8.17 (dd, J = 4.8 Hz, 1.6 Hz,
1H), 7.90 (dd, J = 7.6 Hz, 1.2 Hz, 1H), 7.21-7.29 (m, 2H), 7.20
(d, J = 4.8 Hz, 1H), 7.07 (dd, J = 7.6 Hz, 4.8 Hz, 1H), 7.02 (d,
J = 7.2 Hz, 2H), 6.31 (s, 1H), 5.52 (s, 2H), 2.68 (q, J = 7.2 Hz,
2H), 1.22 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, d6-DMSO)
δ 148.1, 143.5, 141.4, 138.5, 128.6, 127.2, 127.1, 126.4, 119.9,
115.8, 96.2, 43.9, 19.5, 11.8. HRMS (+ESI-TOF) m/z: [M +
Na] + calcd for C16H16N2Na 259.1206, found 259.1200.
+
HRMS (+ESI-TOF) m/z: [M + H] calcd for C22H19N2O2
343.1441, found 343.1428.
1-benzyl-2,5-diphenyl-1H-pyrrolo[2,3-b]pyridine
(3v).
Following General Procedure IV, using 1i (120 mg, 0.415
mmol) and benzylamine (67 mg, 0.62 mmol), the title
compound was obtained (60 mg, 40% yield) as a white solid.
1H NMR (400 MHz, CDCl3) δ 8.58 (d, J = 2.0 Hz, 1H), 8.11
(d, J = 2.0 Hz, 1H), 7.65-7.63 (m, 2H), 7.49-7.34 (m, 8H),
7.24-7.17 (m, 3H), 7.00-6.98 (m, 2H), 6.61 (s, 1H), 5.59 (s,
2H). 13C NMR (100 MHz, CDCl3) δ 149.0, 142.8, 142.6, 139.9,
138.6, 132.4, 130.4, 129.4, 129.1, 128.7, 128.64, 128.61, 127.5,
127.2, 127.1, 126.8, 126.6, 120.7, 100.7, 46.3. HRMS (+ESI-
1-benzyl-2-phenyl-1H-pyrrolo[2,3-b]pyridine
Following General Procedure , using 1d (120 mg, 0.563
mmol) and benzylamine (91 mg, 0.845 mmol), compound 3q
(3q).
1
was obtained (64 mg, 40% yield) as a white solid. H NMR
(400 MHz, d6-DMSO) δ 8.27 (dd, J = 4.8 Hz, 1.6 Hz, 1H),
8.04 (dd, J = 8.0 Hz, 1.2 Hz, 1H), 7.42-7.52 (m, 5H), 7.15-
7.21 (m, 4H), 7.84 (d, J = 7.2 Hz, 2H), 6.68 (s, 1H), 5.59 (s,
2H). 13C NMR (100 MHz, d6-DMSO) δ 148.8, 142.8, 141.2,
138.5, 131.8, 128.8, 128.7, 128.5, 128.4, 128.3, 126.9, 126.1,
120.1, 116.6, 100.3, 45.2. The spectroscopic data are
consistent with data previously reported.25
+
TOF) m/z: [M + H] calcd for C26H21N2 361.1699; found
361.1685.
1-benzyl-6-chloro-2-methyl-1H-pyrrolo[2,3-b]pyridine (3w).
Following General Procedure , using 1j (120 mg, 0.647
mmol) and benzylamine (104 mg, 0.971 mmol), compound 3w

10
Tetrahedron
ACCEPTED MANUSCRIPT
1
was obtained (62 mg, 37% yield) as a yellow solid. H NMR
(400 MHz, CDCl3) δ 7.74 (d, J = 8.0 Hz, 1H), 7.22-7.29 (m,
4H), 7.03-7.06 (m, 3H), 7.23 (d, J = 0.8 Hz, 1H), 5.47 (s, 2H),
2.30 (d, J = 0.8 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 147.8,
143.4, 138.2, 137.8, 129.6, 128.8, 127.5, 126.8, 119.1, 116.0,
98.8, 45.2, 13.3. HRMS (+ESI-TOF) m/z: [M + H] + calcd for
C15H14N2Cl 257.0840, found 257.0834.
77.4, 45.9, 24.8. HRMS (+ESI-TOF) m/z: [M + H] + calcd for
C21H19N2 299.1543; found 299.1530.
1-benzyl-2-phenyl-1H-pyrrolo[2,3-b]quinoline
(3ac).
Following General Procedure , using 1p (120 mg, 0.456
mmol) and benzylamine (98 mg, 0.912 mmol) in DCE at
reflux conditions, compound 3ac was obtained (122 mg, 80%
1
yield) as a yellow solid. H NMR (400 MHz, d6-DMSO) δ
1-benzyl-6-chloro-2-ethyl-1H-pyrrolo[2,3-b]pyridine (3x).
Following General Procedure , using 1k (120 mg, 0.601
mmol) and benzylamine (97 mg, 0.902 mmol), compound 3x
8.61 (s, 1H), 8.08 (d, J = 7.6 Hz, 1H), 7.97 (d, J = 8.8 Hz, 1H),
7.62-7.66 (m, 1H), 7.57-7.59 (m, 2H), 7.43-7.50 (m, 4H),
7.14-7.20 (m, 3H), 6.86-6.89 (m, 3H), 5.70 (s, 2H). 13C NMR
(100 MHz, d6-DMSO) δ 150.6 145.5, 144.4, 138.4, 131.5,
129.0, 128.8, 128.7, 128.43, 128.35, 127.7, 126.9, 126.1, 124.9,
123.0, 121.6, 100.0, 45.3. HRMS (+ESI-TOF) m/z: [M + H] +
calcd for C24H19N2 335.1543, found 335.1534.
1
was obtained (58 mg, 36% yield) as a yellow solid. H NMR
(400 MHz, d6-DMSO) δ 7.97 (d, J = 8.0 Hz, 1H), 7.28-7.33 (m,
2H), 7.24-7.26 (m, 1H), 7.13 (d, J = 8.0 Hz, 1H), 7.00-7.02 (m,
2H), 6.37 (t, J = 0.8 Hz, 1H), 5.47 (s, 2H), 2.63-2.69 (m, 2H),
1.20 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, d6-DMSO) δ
147.1, 144.3, 142.1, 137.8, 130.4, 128.7, 127.2, 126.2, 118.8,
1-benzyl-2-phenyl-4-(trifluoromethyl)-1H-pyrrolo[2,3-
b]pyridine (3ad). Following General Procedure , using 1q
(200 mg, 0.711 mmol) and benzylamine (153 mg, 1.424
mmol) in DCE at reflux conditions, compound 3ad was
115.5, 96.8, 56.0, 44.2, 19.4, 18.6, 11.7. HRMS (+ESI-TOF)
+
m/z: [M + H]
calcd for C16H16N2Cl 271.0997, found
271.0991.
1
obtained (88 mg, 35% yield) as a yellow solid. H NMR (400
1-benzyl-5-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridine (3y).
Following General Procedure , using 1l (120 mg, 0.528
mmol) and benzylamine (85 mg, 0.792 mmol), compound 3y
MHz, CDCl3) δ 8.36 (d, J = 4.4 Hz, 1H), 7.33-7.34 (m, 5H),
7.27 (d, J = 4.8 Hz, 1H), 7.12-7.17 (m, 3H), 6.87 (d, J = 6.4
Hz, 2H), 6.67 (s, 1H), 5.53 (s, 2H). 13C NMR (100 MHz,
CDCl3) δ 150.2, 144.3, 142.8, 138.0, 131.7, 129.5, 129.2,
129.1, 128.8, 128.7, 127.4, 126.7, 125.6 (q, J = 33.0 Hz),
116.5 (q, J = 2.0 Hz), 112.7 (q, J = 4.0 Hz), 99.3, 46.4. HRMS
(+ESI-TOF) m/z: [M + H] + calcd for C21H16N2F3 353.1260,
found 353.1245.
1
was obtained (58 mg, 37% yield) as a yellow oil. H NMR
(400 MHz, d6-DMSO) δ 8.13 (d, J = 1.6 Hz, 1H), 7.84 (s, 1H),
7.40-7.56 (m, 6H), 7.15-7.21 (m, 3H), 6.83 (d, J = 6.8 Hz, 2H),
6.61 (s, 1H), 5.57 (s, 2H), 2.41 (s, 3H). 13C NMR (100 MHz,
d6-DMSO) δ 147.6, 143.6, 141.3, 138.6, 131.9, 128.74, 128.69,
128.43, 128.38, 128. 1, 126.9, 126.0, 125.2, 119.9, 99.8, 45.2,
18.1. HRMS (+ESI-TOF) m/z: [M + H] + calcd for C21H19N2
299.1543, found 299.1535.
1-benzyl-4-methoxy-2-phenyl-1H-pyrrolo[2,3-b]pyridine
(3ae). Following General Procedure , using 1r (120 mg, 0.49
mmol) and benzylamine (79 mg, 0.74 mmol), compound 3ae
1
1-benzyl-4-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridine (3z).
Following General Procedure , using 1m (120 mg, 0.528
mmol) and benzylamine (85 mg, 0.792 mmol), compound 3z
was obtained (8 mg, 5% yield) as a yellow oil. H NMR (400
MHz, CDCl3) δ 8.16 (d, J = 5.6 Hz, 1H), 7.28-7.31 (m, 4H),
7.19 (s, 1H), 7.08-7.12 (m, 3H), 6.87 (d, J = 7.2 Hz, 2H), 6.57
(s, 1H), 5.52 (d, J = 5.6 Hz, 1H), 5.48 (s, 2H), 3.96 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ 159.7, 151.2, 145.2, 139.8, 138.7,
132.6, 129.4, 128.63, 128.58, 128.3, 127.1, 126.6, 110.9, 98.6,
97.8, 55.7, 46.4. HRMS (+ESI-TOF) m/z: [M + H] + calcd for
C21H19N2O 315.1492, found 315.1486.
1
was obtained (55 mg, 35% yield) as a yellow oil. H NMR
(400 MHz, CDCl3) δ 8.23 (d, J = 4.4 Hz, 1H), 7.37-7.38 (m,
5H), 7.16-7.18 (m, 3H), 6.93-6.95 (m, 3H), 6.58 (s, 1H), 5.56
(s, 2H), 2.59 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 149.2,
143.3, 141.2, 139.5, 138.7, 132.7, 129.4, 128.63, 128.57, 128.4,
127.1, 126.6, 121.0, 117.4, 99.0, 46.3, 18.5. HRMS (+ESI-
The regioisomeric amination byproduct (3ae’) was isolated
+
TOF) m/z: [M + H] calcd for C21H19N2 299.1543, found
1
(96 mg, 59% yield) as a yellow solid. H NMR (400 MHz,
299.1539.
CDCl3) δ 8.01 (d, J = 8.0 Hz, 2H), 7.76 (s, 1H), 7.55 (t, J = 7.6
Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 7.31-7.37 (m, 4H), 7.24-7.28
(m, 1H), 5.85 (s, 1H), 4.99 (brs, 1H), 4.49 (s, 2H), 4.10 (s, 2H),
3.68 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 197.7, 165.3,
160.2, 149.4, 139.3, 137.0, 133.1, 128.8, 128.7, 128.4, 127.6,
127.4, 110.3, 88.7, 55.1, 46.8, 37.3. HRMS (+ESI-TOF) m/z:
[M + H] + calcd for C21H21N2O2 333.1598, found 333.1597.
1-benzyl-2,6-dimethyl-1H-pyrrolo[2,3-b]pyridine
(3aa).
Following General Procedure IV, using 1n (120 mg, 0.73
mmol) and benzylamine (117 mg, 1.1 mmol), the title
compound was obtained (107 mg, 62% yield) as a white solid.
1H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 8.0 Hz, 1H), 7.26-
7.18 (m, 3H), 7.03 (d, J = 6.8 Hz, 2H), 6.89 (d, J = 8.0 Hz,
1H), 6.16 (d, J = 0.8 Hz, 1H), 5.50 (s, 2H), 2.59 (s, 3H), 2.27
(s, 3H). 13C NMR (100 MHz, CDCl3) δ 150.7, 148.7, 138.6,
136.5, 128.7, 127.5, 127.2, 126.8, 118.0, 115.9, 98.2, 44.7,
Acknowledgements
Financial support by the Foundation of Tianjin Educational
Committee (No. 2017KJ008) and Tianjin Natural Science
Foundation of China (No. 15JCYBJC53400) is greatly
acknowledged.
+
24.6, 13.3. HRMS (+ESI-TOF) m/z: [M + H] calcd for
C16H17N2 237.1386; found 237.1373.
1-benzyl-6-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridine
(3ab). Following General Procedure IV, using 1o (120 mg,
0.528 mmol) and benzylamine (85 mg, 0.79 mmol), the title
compound was obtained (65 mg, 41% yield) as a white solid.
1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 7.6 Hz, 1H), 7.36-
7.35 (m, 5H), 7.17-7.13 (m, 3H), 6.97 (d, J = 7.6 Hz, 1H),
6.94-6.91 (m, 2H), 6.48 (s, 1H), 5.56 (s, 2H), 2.63 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ 152.2, 149.4, 140.9, 139.0, 132.9,
129.4, 128.6, 128.4, 128.2, 127.0, 126.9, 118.1, 116.6, 100.3,
Supplenmentary Data
Supplementary data (Supplementary data associated with
this article, including materials and methods and NMR spectra)
associated with this article can be found in the online version
at http://dx.doi.org/10.1016/xxx.

11
ACCEPTED MANUSCRIPT
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