Co2(CO)8as a Solid CO (g) Source for the Amino Carbonylation of (Hetero)aryl Halides with Highly Deactivated (Hetero)arylamines

Article abstract of DOI:10.1021/acs.joc.0c02999

Carbonylation of (hetero)aryl iodides/bromides with highly deactivated 2-aminopyridines using Pd-Co(CO)4 bimetallic catalysis is accomplished. The use of Co2(CO)8 as a solid CO(g) source enhanced reaction rates observed when compared to CO(g), and excellent yields highlight the versatility of the developed protocol. A wide range of electronically and sterically demanding heterocyclic amines and (hetero)aryl iodides/bromides employed for this study resulted in excellent yields of amino carbonylated products. The developed methodology was further extended to synthesize Trypanosome brucie and luciferase inhibitors.

Full text of DOI:10.1021/acs.joc.0c02999

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Article
Co2(CO)8 as a Solid CO (g) Source for the Amino Carbonylation of
(Hetero)aryl Halides with Highly Deactivated (Hetero)arylamines
Srinivas Cheruku, Ayyiliath M Sajith, Yatheesh Narayana, Poornima Shetty, Sandhya C Nagarakere,
Kunigal S Sagar, Kumara N Manikyanally, Kanchugarkoppal Subbegowda Rangappa,*
and Kempegowda Mantelingu*
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ABSTRACT: Carbonylation of (hetero)aryl iodides/bromides
with highly deactivated 2-aminopyridines using Pd−Co(CO)4
bimetallic catalysis is accomplished. The use of Co2(CO)8 as a
solid CO(g) source enhanced reaction rates observed when
compared to CO(g), and excellent yields highlight the versatility
of the developed protocol. A wide range of electronically and
sterically demanding heterocyclic amines and (hetero)aryl iodides/
bromides employed for this study resulted in excellent yields of amino carbonylated products. The developed methodology was
further extended to synthesize Trypanosome brucie and luciferase inhibitors.
applicable to a broad range of (hetero)aryl halides/
pseudohalides with various electronic and steric properties
still remains a major challenge. Notably, the use of sluggish and
less nucleophilic amino counterparts (2-aminopyridine) with
CO(g) surrogates is not well explored. The presence of an N-
(pyridin-2-yl)benzamide moiety as a vital pharmacophore in
many biologically relevant compounds (luciferase inhibitor,
antiulcer agent, etc.) and its use in the treatment of
osteoarthritis (Figures 1 and 2)10,11 warrants the development
of an efficient carbonylation protocol that allows the facile
incorporation of sluggish and less nucleophilic 2-amino-
pyridines. Considering the biochemical utility of these amino
carbonylated products and as a part of our continuing research
on the synthesis of heterocyclic and bioactive compounds via
INTRODUCTION
■
Amides are naturally occurring biomolecules, having immense
significance due to their biological, agrochemical, and
pharmaceutical applications.1,2 Consequently, development of
synthetic approaches that allows the facile incorporation of this
vital functional group is of immense potential. Conventional
methods employed for the synthesis of (hetero)aryl amides
include the reaction of activated (hetero)aryl carboxylic acid
derivatives (acyl halides, esters, anhydrides)2 with (hetero)aryl
amines. The development of several activating agents that can
activate the carboxylic acid group has expanded the substrate
scope of this important methodology. Conversely, the use of
electron-deficient or less nucleophilic amines are still remains a
major challenge under these reaction conditions.
Additional synthetic methodologies for accessing this vital
amide functionality involve the palladium-mediated amino
carbonylation of (hetero)aryl halides using of toxic CO(g)
under high-pressure conditions.3 However, the use of poison-
ous CO(g), the requirement of high-pressure equipment and
special handling techniques, and safety issues associated with
this technology have limited its application in small-scale
industries and academic laboratories, although advances in
these surrogates have been seen (sila carboxylic acids,4 metal
carbonyls,5 chloroform,6 acid chlorides,7 oxalat,e8 etc.).
Figure 1. Drug molecules containing deactivated N-(pyridin-2-
yl)amides.
Among the various technologies developed, the use of near-
stoichiometric CO(g) for a variety of carbonylation processes
developed by Skrtydstrup et al.9 is noteworthy. The method
involves the use of a two-chamber system where a decarbon-
ylation event takes place in one chamber and CO(g) generated
was delivered as a reagent in the other chamber. Despite these
advancements in the carbonylation technology, the need for an
operationally simple and general catalytic system which is
Received: January 6, 2021
Published: April 7, 2021
https://doi.org/10.1021/acs.joc.0c02999
© 2021 American Chemical Society
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RESULTS AND DISCUSSION
■
Our reaction optimization strategy was focused on the amino
carbonylation of iodobenzene using Co2(CO)8 as the CO(g)
source and 2-aminopyridine as the nucleophilic coupling
partner. From the initial screening of the catalytic systems and
our previous studies, the superior reactivity of palladium-based
bidentate catalytic species was well established.14 Accordingly,
from our initial screening studies using Pd/bidentate ligands,
PdCl2(dppf)·CH2Cl2 resulted in excellent yields of the amino
carbonylated products. Among the bases screened, the use of
organic base DBU was found to be instrumental in driving the
reactions to completion. Our initial efforts to perform a room-
temperature carbonylation protocol, however, resulted in poor
isolated yields. The use of monodentate phosphine ligands also
afforded the carbonylated products with poor isolated yields
(Table 1, entries 16, 18, and 19). However, our trials in
attaining a ligand-free carbonylation protocol were in vain as
we could see only little product formation (Table 1, entry 14).
The lower yields of the carbonylated products using
monodentate ligands when compared to bidentate ligands
can be attributed to the bite angle that facilitates the cis
geometry of the oxidative adduct complex. The cis geometry
would probably facilitate the facile CO insertion from the
bimetallic species (Scheme 1), and thus, enhanced reaction
rates were observed in our experiments. Among the metal
Figure 2. Synthesis of N-(pyridine-2-yl)amides.
novel methodologies,12,13 our research was focused on
development of an amino carbonylation protocol under low
pressure using substoichiometric Co2(CO)8 as the CO(g)
surrogate. The low-pressure carbonylation procedures would
thus obviate the possible formation of palladium carbonyl
clusters that can potentially lead to catalyst deactivation.
Table 1. Optimization of Reaction Conditions
entry
catalyst (mol %)
ligand (mol %)
base
solvent
CO source
temp (°C)
yield (%)
1
2
3
4
5
6
7
8
PdCl2dppf·CH2Cl2 (5)
PdCl2dppf·CH2Cl2 (5)
PdCl2dppf·CH2Cl2 (5)
PdCl2dppf·CH2Cl2 (5)
PdCl2dppf·CH2Cl2 (5)
PdCl2dppf·CH2Cl2 (5)
PdCl2dppf·CH2Cl2 (5)
PdCl2dppf·CH2Cl2 (5)
PdCl2dppf·CH2Cl2 (5)
PdCl2dppf·CH2Cl2 (5)
PdCl2dppf·CH2Cl2 (5)
PdCl2dppf·CH2Cl2 (3)
PdCl2dppf·CH2Cl2 (10)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
NaOAc
NaOAc
NaOAc
NaOAc
KOAc
Na2CO3
K2CO3
Et3N
DABCO
DMAP
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
DMF
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co2(CO)8
Cr(CO)6
rt
60
20
30
50
45
60
30
47
49
65
60
80
65
78
23
57
48
59
63
54
68
60
55
70
40
54
44
10
69
110
130
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
Xanthphos (5)
XPhos (5)
BINAP (5)
P(tBu)3 (5)
P(Cy)3 (5)
Dppf (5)
PdCl2dppf·CH2Cl2 (5)
PdCl2dppf·CH2Cl2 (5)
PdCl2dppf·CH2Cl2 (5)
PdCl2dppf·CH2Cl2 (5)
PdCl2dppf·CH2Cl2 (5)
PdCl2dppf·CH2Cl2 (5)
PdCl2dppf·CH2Cl2 (5)
PdCl2dppf·CH2Cl2 (5)
DBU
DBU
DBU
DBU
DBU
DBU
DBU
toluene
DME
THF
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
W(CO)6
Fe(CO)5
Mo(CO)6
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carbonyls studied, the use of Co2(CO)8 yielded the best
results.
Scheme 2. Scope of Aminopyridine for the Amino
Carbonylation with Aryl Iodides/Bromides
Scheme 1. Plausible Mechanism for the Amino
Carbonylation
Our control experiments to perform the carbonylation using
CO(g) generated in a two-chamber apparatus {(CO(g)
generated in one chamber from Co2(CO)8 and DBU was
passed to the other chamber containing all the reactants except
cobalt carbonyl} resulted in little product formation. These
control experiments clearly indicate the dual role of Co2(CO)8
of acting as a CO(g) source as well as playing a pivotal role in
the catalytic cycle.
The optimized reaction conditions were further investigated
for their substrate scope potential. A wide range of electroni-
cally biased (hetero)aryl iodides and bromides yielded the
carbonylated products with 2-aminopyridine in excellent
isolated yields (Scheme 2). Notably, different functionalities
like ester, sulfonamides, etc. were well tolerated under the
reaction conditions (Scheme 2). The successful amino
carbonylation of sterically demanding 2,6-substituted bromo-
benzene and pharmaceutically relevant halo heterocycles
(quinoline, pyrimidine) with 2-aminopyridine further high-
lights the versatility of the optimized protocol. To further
evaluate the scope and limitations of the methodology, a broad
range of challenging and electronically deactivated (hetero)-
arylamines were surveyed as nucleophilic coupling partners.
Surprisingly, with most of the studied heterocyclic amino
nucleophiles excellent yields of the amino carbonylated
products were obtained (Scheme 3).
The use of multiheteroatom-containing substrates in
palladium-mediated reactions is a major hurdle due to possible
binding of these heteroatoms to palladium, leading to catalyst
deactivation. In our successful trials, we have achieved the
facile carbonylation of (hetero)aryl halides with highly
deactivated heterocyclic amine nucleophiles containing multi-
heteroatoms (Scheme 3). These results clearly indicate the
catalytic efficiency of this overall catalytic process and thereby
allow the synthesis of highly decorated heterocyclic architec-
tures. To further expand the substrate scope with respect to the
electrophilic coupling partner, the protocol was further
a
b
Aryl iodide was used. Aryl bromide was used.
extended to aryl triflates15 and aryl chlorides. To our delight,
the use of 4-methoxyaryl triflate resulted in 68% product
formation (Scheme 4). Chemoselective carbonylation of 4-
iodobromobenzene with 2-aminopyridine (Scheme 4) further
corroborates the excellent synthetic versatility of the developed
methodology. The practical utility of our method was further
shown by performing a gram-scale synthesis of amide
derivative 3e in 72% yield, and the crystal for the same was
obtained (Figure 3).
CONCLUSIONS
■
Expedient amino carbonylation of (hetero)aryl halides with
highly deactivated and multiheteroatom containing amine
nucleophiles using substoichiometric Co2(CO)8 was devel-
oped. The broad substrate scope, excellent Chemoselectivity,
mild reaction conditions, and more importantly the facile CO
insertion from a bimetallic catalytic species (Pd-CO) are the
major highlights of this technology.
EXPERIMENTAL SECTION
■
General Information. All of the reagents, chemicals, and solvents
used were from Sigma-Aldrich and Sd-fine chemicals. The
instrumental techniques employed for the characterization of the
newly synthesized compounds include 1H and 13C NMR and HRMS.
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Scheme 3. Substrate Scope for the Synthesis of Amides
Figure 3. ORTEP diagram of the compound 3e.
1H and 13C NMR spectra were recorded on Agilent 400 MHz
spectrometer in DMSO-d6 solution using tetramethylsilane (TMS) as
internal standard. Chemical shifts were recorded in ppm relative to
TMS. High-resolution mass spectra were obtained from the Waters
Xevo-G2-XS via electrospray ionization time-of-flight (ESI-TOF).
Column chromatography was performed on silica gel 60 (60−120
mesh), and thin-layer chromatography was performed on TLC plates
(Merck, silica gel 60 F254).
General Procedure for Synthesis of Amides. To a Schlenk
tube equipped with a magnetic stirring bar and a Teflon septum were
charged aniline (1.06 mmol), aryl halide (1.2 mmol), DBU (2.65
mmol, 2.5 equiv), and dioxane (2 mL). Under an inert atmosphere
was added PdCl2(dppf)·CH2Cl2 (5 mol %, 0.05 equiv) followed by
Co2(CO)8 (0.424 mmol, 0.4 equiv) (CO gas is poisonous gas, handle
with care or read MSDL for safety measures). (Note: soon after
addition of Co2(CO)8 the effervescence of CO gas is observed5a).
The tube was closed immediately with a Teflon srew cap and was
heated to 110 °C overnight by using an oil bath. The reaction was
monitored by TLC to make sure that starting material was consumed.
The reaction mixture was diluted with water (5 mL) and extracted
with ethyl acetate (2 × 5 mL). The combined organic layers were
washed with brine solution (10 mL), dried over sodium sulfate,
filtered, and concentrated under reduced pressure, and the desired
product was isolated by silica gel column chromatography using
eluents EtOAc/hexane (30:70).
Control Experiment for the Mechanistic Study. In a two-
chamber apparatus equipped with magnetic beads and a Teflon
septum, one chamber was charged with pyridin-2-amine (250 mg,
2.65 mmol, 1.0 equiv), 1-bromo-4-iodobenzene (901 mg, 3.18 mmol,
1.2 equiv), PdCl2(dppf)·CH2Cl2 (108 mg, 0.13 mmol, 0.05 equiv),
and dioxane (5 mL) under an inert atmosphere, and the chamber was
closed with a Teflon screw cap. Later, the other chamber was charged
with DBU (0.98 mL, 6.63 mmol; 2.5 equiv) in dioxane (3 mL)
followed by Co2(CO)8 (0.37 g, 1.06 mmol; 0.4 equiv) under an inert
atmosphere, and the chamber was closed immediately with a Teflon
screw cap. The reaction mixture was stirred at room temperature
overnight. The reaction was found to be sluggish by TLC with a trace
amount conversion. (Note: When the same reaction was performed in
a single chamber apparatus, an excellent yield resulted (73%, Scheme
4, example 3p).)
a
b
Aryl iodide was used. Aryl bromide was used.
Scheme 4. Chemoselectivity Experiments for the Amino
Carbonylation
Scale Up Procedure for Synthesis of Compound 3e. To a
Schlenk tube equipped with magnetic stirring bar and a Teflon
septum were charged pyridin-2-amine (2 g, 21.27 mmol, 1.0 equiv),
methyl 4-bromobenzoate (5.4 g, 25.53 mmol,1.2 equiv), DBU (7.9
mL, 53.17 mmol; 2.5 equiv), and dioxane (40 mL, 20 vol) Under an
inert atmosphere was added PdCl2(dppf)·CH2Cl2 (867 mg, 1.06
mmol, 0.05 equiv) followed by Co2(CO)8 (2.9 g, 8.5 mmol; 0.4
equiv). The tube was closed immediately with a Teflon screw cap and
heated to 110 °C overnight with an oil bath. The reaction was
monitored by TLC to make sure that starting material was consumed.
The reaction mixture was diluted with water (30 mL) and extracted
with ethyl acetate (2 × 40 mL). The combined organic layers were
dried over sodium sulfate, filtered, and concentrated under reduced
pressure, and the crude material was purified through silica gel
column chromatography (eluents: hexane/EtOAc; 80:20) to afford
methyl 4-(pyridin-2-ylcarbamoyl)benzoate (3.97 g, 15.5 mmol, 72%
yield).
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Characterization Data of the Isolated Compounds. N-
(Pyridin-2-yl)benzamide (3a). The title compound was synthesized
by using pyridin-2-amine and 1-iodobenzene by following the general
procedure. Eluent: EtOAc/hexane 30:70; yield: 168 mg, 80%; off
white solid; 1H NMR (400 MHz, DMSO-d6) δ 10.75 (s, 1H), 8.36−
8.37 (m, 1H), 8.22 (d, J = 8.0 Hz, 1H), 8.05 (d, J = 8.0 Hz, 2H),
7.79−7.83 (m, 1H), 7.54−7.58 (m, 1H), 7.47−7.50 (m, 2H), 7.11−
7.14 (m, 1H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 166.4, 152.6,
148.3, 138.5, 134.5, 132.3, 128.7, 128.4, 120.2, 115.2; HRMS (ESI-
TOF) m/z [M + H]+ calcd for C12H11N2O 199.0866, found
199.0865.
HRMS (ESI-TOF) m/z [M + H]+ calcd for C13H10F3N2O 267.0740,
found 267.0748.
6-Methyl-N-(pyridin-2-yl)pyridine-2-carboxamide (3h). The title
compound was synthesized using pyridin-2-amine and 2-bromo-6-
methylpyridine following the general procedure. Eluent: EtOAc/
1
hexane 40:60; yield: 165 mg, 73%; brown gummy mass; H NMR
(400 MHz, DMSO-d6) δ 10.37 (s, 1H), 8.35 (d, J = 8.0 Hz, 1H), 8.25
(d, J = 8.0 Hz, 1H), 7.83−7.97 (m, 3H), 7.5 (d, J = 8.0 Hz, 1H),
7.14−7.17 (m, 1H), 2.57 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-
d6) δ 162.4, 157.9, 151.1, 148.9, 148.3, 139.1, 138.9, 127.6, 120.6,
119.9, 113.5, 24.3; HRMS (ESI-TOF) m/z [M + H]+ calcd for
C12H12N3O 214.0975, found 214.0969.
4-Methoxy-N-(pyridin-2-yl)benzamide (3b). The title compound
was synthesized using pyridin-2-amine and 1-iodo-4-methoxybenzene
following the general procedure. Eluent: EtOAc/hexane 30:70; yield:
2-Methyl-N-(pyridin-2-yl)benzo[d]oxazole-5-carboxamide (3i).
The title compound was synthesized using pyridin-2-amine and 5-
bromo-2-methylbenzo[d]oxazole following the general procedure.
1
189 mg, 78%; white solid; H NMR (400 MHz, DMSO-d6) δ 10.58
1
(s, 1H), 8.36−8.37 (m, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.06 (d, J = 8.0
Hz, 2H), 7.79−7.83 (m, 1H), 7.09−7.14 (m, 1H), 7.03 (d, J = 8.0 Hz,
2H), 3.82 (s, 3H); 13C{1H} (100 MHz, DMSO-d6) δ 165.9, 162.8,
152.9, 148.4, 138.6, 130.6, 126.7, 120.1, 115.2, 114.1, 55.9; HRMS
(ESI-TOF) m/z [M + H]+ calcd for C13H13N2O2 229.0972, found
229.0967.
Eluent: EtOAc/hexane 30:60; yield: 185 mg, 69%; brown solid; H
NMR (400 MHz, DMSO-d6) δ 10.85 (s, 1H), 8.36- 8.39 (m, 2H),
8.19 (d, J = 8.0 Hz, 1H), 8.03−8.05 (m, 1H), 7.82−7.84 (m, 1H),
7.74−7.76 (m, 1H), 7.15−7.18 (m, 1H), 2.65 (s, 3H); 13C{1H} NMR
(100 MHz, DMSO-d6) δ 166.1, 165.9, 153.1, 152.8, 148.5, 141.6,
138.6, 131.0, 125.7, 120.3, 119.7, 115.4, 110.7,14.7; HRMS (ESI-
TOF) m/z [M + H]+ calcd for C14H12N3O2 254.0924, found
254.0928.
2-Ethoxy-N-(pyridin-2-yl)pyrimidine-5-carboxamide (3c). The
title compound was synthesized using pyridin-2-amine and 5-
bromo-2-ethoxypyrimidine following the general procedure. Eluent:
2-Methyl-N-(pyridin-2-yl)benzo[d]thiazole-5-carboxamide (3j).
The title compound was synthesized using pyridin-2-amine and 5-
bromo-2-methylbenzo[d]thiazole following the general procedure.
1
EtOAc/hexane 25:75; yield: 186 mg, 72%; an off white solid; H
NMR (400 MHz, DMSO-d6) δ 11.02 (s, 1H), 9.10 (s, 2H), 8.36 (d, J
= 4.0 Hz, 1H), 8.15 (d, J = 8.0 Hz, 1H), 7.80−7.84 (m, 1H), 7.14−
7.17 (m, 1H), 4.38−4.43 (m, 2H), 1.31−1.35 (m, 3H); 13C{1H}
NMR (100 MHz, DMSO-d6) δ 166.2, 163.1, 160.2, 152.3, 148.4,
138.6, 122.3, 120.4, 115.0, 64.1, 14.6; HRMS (ESI-TOF) m/z [M +
H]+ calcd for C12H13N4O2 245.1033, found 245.1040.
1
Eluent: EtOAc/hexane 25:75; yield: 180 mg, 63%; white solid; H
NMR (400 MHz, DMSO-d6) δ 10.93 (s, 1H), 8.58 (s, 1H), 8.40 (d, J
= 2.8 Hz, 1H), 8.22 (d, J = 8.0 Hz, 1H), 8.14 (d, J = 8.0 Hz, 1H), 8.03
(d, J = 8.0 Hz, 1H), 7.83−7.87 (m, 1H), 7.15−7.18 (m, 1H), 2.83 (s,
3H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 168.9, 166.1, 153.1,
152.6, 148.3, 139.4, 138.5, 132.6, 124.6, 122.3, 122.0, 120.2, 115.2,
20.3; HRMS (ESI-TOF) m/z [M + H]+ calcd for C14H12N3OS
270.0696, found 270.0693.
4-(Dimethylamino)-N-(pyridin-2-yl)benzamide (3d). The title
compound was synthesized using pyridin-2-amine and 4-bromo-
N,N-dimethylbenzenamine following the general procedure. Eluent:
1
EtOAc/hexane 40:60; yield: 166 mg, 65%; brown solid; H NMR
2,3-Dihydro-2-oxo-N-(pyridin-2-yl)benzo[d]oxazole-6-carboxa-
mide (3k). The title compound was synthesized using pyridin-2-
amine and 6-bromobenzo[d]oxazol-2(3H)-one following the general
procedure. Eluent: EtOAc/hexane 30:70; yield: 208 mg, 77%; an off
(400 MHz, DMSO-d6) δ 10.27 (s, 1H), 8.32 (d, J = 4.0 Hz, 1H), 8.17
(d, J = 8.0 Hz, 1H), 7.94 (d, J = 8.8 Hz, 2H), 7.74−7.79 (m, 1H),
7.06−7.09 (m, 1H), 6.70 (d, J = 8.8 Hz, 2H), 2.97 (s, 6H); 13C{1H}
NMR (100 MHz, DMSO-d6) δ 165.8, 153.1, 153.0, 148.1, 138.2,
129.9, 120.5, 119.5, 114.9, 111.1, 40.6; HRMS (ESI-TOF) m/z [M +
H]+ calcd for C14H16N3O 242.1288, found 242.1285.
1
white solid; H NMR (400 MHz, DMSO-d6) δ 11.95 (br, s, 1H),
10.69 (s, 1H); 8.35 (d, J = 3.6 Hz, 1H); 8.14 (d, J = 8.0 Hz, 1H); 7.96
(s, 1H), 7.89 (d, J = 8.0 Hz, 1H); 7.78−7.81 (m, 1H), 7.13−7.17 (m,
2H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 165.6, 155.0, 152.8,
148.4, 143.5, 138.6, 134.3, 128.3, 125.3, 120.3, 115.3, 109.8, 109.6;
HRMS (ESI-TOF) m/z [M + H]+ calcd for C13H10N3O3 256.0717,
found 256.0723.
Methyl 4-(Pyridin-2-ylcarbamoyl)benzoate (3e). The title com-
pound was synthesized using pyridin-2-amine and methyl 4-
bromobenzoate following the general procedure. Eluent: EtOAc/
1
hexane 20:80; yield: 204 mg, 75%; an off white solid; H NMR (400
MHz, DMSO-d6) δ 10.98 (s, 1H), 8.39−8.41 (m, 1H), 8.19 (d, J =
8.0 Hz, 1H), 8.13 (d, J = 8.0 Hz, 2H), 8.06 (d, J = 4.0 Hz, 2H), 7.84−
7.88 (m, 1H), 7.17−7.20 (m, 1H), 3.90 (s, 3H); 13C{1H} NMR (100
MHz, DMSO-d6) δ 166.2, 165.8, 152.5, 148.6, 138.8, 138.7, 132.8,
129.6, 128.9, 120.6, 115.3, 53.0; HRMS (ESI-TOF) m/z [M + H]+
calcd for C14H13N2O3 257.0921, found 257.0927.
N-(Pyridin-2-yl)benzo[d][1,3]dioxole-5-carboxamide (3l). The
title compound was synthesized using pyridin-2-amine and 5-
bromobenzo[d][1,3]dioxole following the general procedure. Eluent:
1
EtOAc/hexane 30:60; yield: 190 mg, 74%; brown gummy mass; H
NMR (400 MHz, DMSO-d6) δ 10.56 (s, 1H), 8.34 (d, J = 2.0 Hz,
1H); 8.14 (d, J = 8.8 Hz, 1H), 7.77−7.81 (m, 1H), 7.64−7.66 (m,
1H), 7.58 (s, 1H), 7.10−7.12 (m, 1H), 6.98−7.00 (m, 1H), 6.10 (s,
2H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 165.3, 152.7, 150.8,
148.2, 147.8, 138.4, 128.2, 123.8, 120.1, 115.1, 108.4, 102.2; HRMS
(ESI-TOF) m/z [M + H]+ calcd for C13H11N2O3 243.0764, found
243.0761.
4-(Cyclopropanesulfonamido)-N-(pyridin-2-yl)benzamide (3f).
The title compound was synthesized using pyridin-2-amine and N-
(4-bromophenyl)cyclopropanesulfonamide following the general
procedure. Eluent: EtOAc/hexane 70:30; yield: 198 mg, 59%;
1
brown gummy mass; H NMR (400 MHz, DMSO-d6) δ 10.61 (s,
1H), 10.18 (s, 1H), 8.34 (s, 1H), 8.17 (d, J = 8.0 Hz, 1H), 8.02 (d, J =
8.0 Hz, 2H), 7.77−7.81 (m, 1H); 7.31 (d, J = 8.0 Hz, 2H), 7.11 (s,
1H), 2.70 (s, 1H), 0.94−0.98 (m, 4H); 13C{1H} NMR (100 MHz,
DMSO-d6) δ 165.6, 152.7, 148.2, 142.3, 138.4, 129.8, 129.0, 120.0,
118.6, 115.1, 30.4, 5.5; HRMS (ESI-TOF) m/z [M + H]+ calcd for
C15H16N3O3S 318.0907, found 318.0903.
N-(Pyridin-2-yl)quinoline-2-carboxamide (3m). The title com-
pound was synthesized using pyridin-2-amine and 2-bromoquinoline
following the general procedure. Eluent: EtOAc/hexane 40:60; yield:
1
209 mg, 79%; an off white solid; H NMR (400 MHz, DMSO-d6) δ
10.57 (s, 1H), 8.60 (d, J = 8.0 Hz, 1H), 8.39 (d, J = 4.0 Hz, 1H), 8.29
(d, J = 8.0 Hz, 1H), 8.24 (d, J = 8.0 Hz, 1H), 8.2 (d, J = 8.0 Hz, 1H),
8.07 (d, J = 8.0 Hz, 1H), 7.85−7.90 (m, 2H), 7.70−7.74 (m, 1H),
7.17−7.20 (m, 1H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 162.6,
151.1, 149.1, 148.9, 146.2, 139.2, 139.1, 131.4, 129.9, 129.7, 129.2,
128.6, 120.7, 118.8, 113.7; HRMS (ESI-TOF) m/z [M + H]+ calcd
for C15H12N3O 250.0975, found 250.0969.
N-(Pyridin-2-yl)isoquinoline-6-carboxamide (3n). The title com-
pound was synthesized using pyridin-2-amine and 6-bromoisoquino-
line following the general procedure. Eluent: EtOAc/hexane 45:55;
2-(Trifluoromethyl)-N-(pyridin-2-yl)benzamide (3g). The title
compound was synthesized using pyridin-2-amine and 1-bromo-2-
(trifluoromethyl)benzene following the general procedure. Eluent:
1
EtOAc/hexane 20:80; yield: 189 mg, 67%; brown solid; H NMR
(400 MHz, DMSO-d6) δ 11.11 (s, 1H), 8.3 (d, J = 4.0 Hz, 1H); 8.19
(d, J = 8.0 Hz, 1H), 7.80−7.93 (m, 2H), 7.67−7.77 (m, 3H), 7.14−
7.17 (m, 1H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 167.1, 152.3,
148.6, 138.3, 136.3, 132.9, 130.6, 129.1, 126.8, 126.5, 120.6, 114.8;
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yield: 164 mg, 62%; brown gummy mass; 1H NMR (400 MHz,
DMSO-d6) δ 11.05 (s, 1H), 9.40 (s, 1H), 8.60−8.65 (m, 2H), 8.39 (s,
1H), 8.21−8.23 (m, 3H), 7.85−7.94 (m, 2H), 7.17 (s, 1H); 13C{1H}
NMR (100 MHz, DMSO-d6) δ 166.1, 152.7, 152.4, 148.4, 144.0,
138.6, 136.0, 134.8, 128.2, 127.5, 126.5, 121.7, 120.4, 115.1; HRMS
(ESI-TOF) m/z [M + H]+ calcd for C15H12N3O 250.0975, found
250.0979.
2,4,6-Trimethyl-N-(pyridin-2-yl)benzamide (3o). The title com-
pound was synthesized using pyridin-2-amine and 2-bromo-1,3,5-
trimethylbenzene following the general procedure. Eluent: EtOAc/
hexane 20:80; yield: 150 mg, 59%; yellow solid; 1H NMR (400 MHz,
DMSO-d6) δ 10.72 (s, 1H), 8.28 (d, J = 4.0 Hz, 1H), 8.20 (d, J = 8.0
Hz, 1H), 7.8 (t, J = 8.0 Hz, 1H), 7.1 (t, J = 8.0 Hz, 1H), 6.87 (s, 2H),
2.23 (s, 3H), 2.20 (s, 6H); 13C{1H} NMR (100 MHz, DMSO-d6) δ
169.1, 152.0, 148.1, 138.1, 137.6, 135.4, 133.6, 127.8, 119.8, 114.4,
20.7, 18.9; HRMS (ESI-TOF) m/z [M + H]+ calcd for C15H17N2O
241.1335, found 241.1326.
2H), 7.84 (d, J = 5.6 Hz, 1H), 7.56−7.59 (m, 1H), 7.46−7.50 (m,
2H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 167.4, 165.2, 160.7,
160.6, 133.8, 132.8, 128.7, 104.8, 54.8; HRMS (ESI-TOF) m/z [M +
H]+ calcd for C12H12N3O2 230.0924, found 230.0929.
N-(5-Methylpyrazin-2-yl)benzamide (3v). The title compound
was synthesized using 5-methylpyrazin-2-amine and 1-iodobenzene
following the general procedure. Eluent: EtOAc/hexane 50:50; yield:
121 mg, 62%; brown solid; 1H NMR (400 MHz, DMSO-d6) δ 10.96
(s, 1H), 9.30 (s, 1H), 8.33 (s, 1H), 8.05 (d, J = 8.4 Hz, 2H), 7.57−
7.61 (m, 1H), 7.49−7.53 (m, 2H), 2.48 (s, 3H); 13C{1H} NMR (100
MHz, DMSO-d6) δ 166.5, 149.0, 147.2, 142.1, 136.8, 134.1, 132.7,
129.2, 128.9, 20.9; HRMS (ESI-TOF) m/z [M + H]+ calcd for
C12H12N3O 214.0975, found 214.0971.
N-(5-Cyclopropyl-1,3,4-thiadiazol-2-yl)benzamide (3w). The title
compound was synthesized using 5-cyclopropyl-1,3,4-thiadiazol-2-
amine and 1-iodobenzene following the general procedure. Eluent:
1
EtOAc/hexane 50:50; yield: 100 mg, 58%; brown solid; H NMR
4-Bromo-N-(pyridin-2-yl)benzamide (3p). The title compound
was synthesized using pyridin-2-amine and 1-bromo-4-iodobenzene
following the general procedure. Eluent: EtOAc/hexane 25:75; yield:
213 mg, 73%; brown solid; 1H NMR (400 MHz, DMSO-d6) δ 10.85
(s, 1H), 8.37 (d, J = 3.6 Hz, 1H); 8.15 (d, J = 8.0 Hz, 1H), 7.94 (d, J
= 8.0 Hz, 2H), 7.80−7.84 (m, 1H), 7.69 (d, J = 8.0 Hz, 2H), 7.14−
7.17 (m, 1H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 165.5, 152.4,
148.4, 138.5, 133.7, 131.7, 130.5, 126.1, 120.3, 115.2; HRMS (ESI-
TOF) m/z [M + H]+ calcd for C12H10BrN2O 276.9971, found
276.9978.
(400 MHz, DMSO-d6) δ 12.90 (s, 1H), 8.09 (d, J = 7.2 Hz, 2H),
7.63−7.66 (m, 1H), 7.52−7.56 (m, 2H), 2.39−2.43 (m, 1H), 1.12−
1.17 (m, 2H), 0.99−1.03 (m, 2H); 13C{1H} NMR (100 MHz,
DMSO-d6) δ 167.5, 165.6, 158.3, 133.4, 132.2, 129.2, 128.9, 29.6,
11.1, 10.8; HRMS (ESI-TOF) m/z [M + H]+ calcd for C12H12N3OS
246.0696, found 246.0694.
N-(Thiazol-2-yl)benzamide (3x). The title compound was
synthesized using thiazol-2-amine and 1-iodobenzene following the
general procedure. Eluent: EtOAc/hexane 25:75; yield: 140 mg, 69%;
1
brown gummy mass; H NMR (400 MHz, DMSO-d6) δ 12.64 (s,
4-Chloro-3-fluoro-N-(pyridin-2-yl)benzamide (3q). The title
compound was synthesized using pyridin-2-amine and 4-bromo-1-
chloro-2-fluorobenzene following the general procedure. Eluent:
1H), 8.09−8.11 (m, 2H), 7.60−7.64 (m, 1H), 7.51−7.57 (m, 3H),
7.27−7.28 (m, 1H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 165.6,
159.3, 138.2, 133.1, 132.8, 129.1, 128.7, 114.4; HRMS (ESI-TOF) m/
z [M + H]+ calcd for C10H9N2OS 205.0430, found 205.0441.
N-(4-Cyanothiazol-2-yl)benzamide (3y). The title compound was
synthesized using 2-aminothiazole-4-carbonitrile and 1-iodobenzene
following the general procedure. Eluent: EtOAc/hexane 40:60; yield:
119 mg, 65%; brown solid; 1H NMR (400 MHz, DMSO-d6) δ 13.09
(s, 1H), 8.42 (s, 1H), 8.10 (d, J = 9.2 Hz, 2H), 7.65−7.67 (m, 1H),
7.54−7.58 (m, 2H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 166.3,
160.5, 133.6, 131.8, 129.2, 128.8, 128.1, 121.0, 115.5; HRMS (ESI-
TOF) m/z [M + H]+ calcd for C11H8N3OS 230.0383, found
230.0378.
N-(3-Methyl-1,2,4-thiadiazol-5-yl)benzamide (3z). The title com-
pound was synthesized using 3-methyl-1,2,4-thiadiazol-5-amine and 1-
iodobenzene following the general procedure. Eluent: EtOAc/hexane
35:65; yield: 135 mg, 71%; brown gummy mass; 1H NMR (400 MHz,
DMSO-d6) δ 13.3 (s, 1H), 8.13 (d, J = 8.0 Hz, 2H), 7.65−7.69 (m,
1H), 7.55−7.58 (m, 2H), 2.48 (s, 3H); 13C{1H} NMR (100 MHz,
DMSO-d6) δ 176.3, 168.0, 166.9, 133.9, 131.2, 129.3, 128.9, 19.3;
HRMS (ESI-TOF) m/z [M + H]+ calcd for C10H10N3OS 220.0539,
found 220.0535.
1
EtOAc/hexane 20:80; yield: 180 mg, 68%; brown solid; H NMR
(400 MHz, DMSO-d6) δ 10.93 (s, 1H), 8.37 (d, J = 4.0 Hz, 1H), 8.13
(d, J = 8.0 Hz, 1H), 8.01−8.04 (m, 1H), 7.81−7.87 (m, 2H), 7.70−
7.74 (m, 1H), 7.15−7.18 (m, 1H); 13C{1H} NMR (100 MHz,
DMSO-d6) δ 163.9, 158.2, 155.7, 151.9, 148.1, 138.3, 135.0, 130.8,
125.4, 123.5, 120.2, 116.6, 114.9; HRMS (ESI-TOF) m/z [M + H]+
calcd for C12H9ClFN2O 251.0382, found 251.0387.
2-Chloro-N-(pyridin-2-yl)pyridine-4-carboxamide (3r). The title
compound was synthesized using pyridin-2-amine and 4-bromo-2-
chloropyridine following the general procedure. Eluent: EtOAc/
1
hexane 40:60; yield: 163 mg, 66%; yellow gummy mass; H NMR
(400 MHz, DMSO-d6) δ 11.18 (s, 1H), 8.56 (d, J = 3.6 Hz, 1H), 8.39
(s, 1H), 8.14−8.15 (m, 1H), 8.01 (s, 1H), 7.83−7.87 (m, 2H), 7.18
(s, 1H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 163.7, 151.9, 151.2,
150.9, 148.1, 145.2, 138.7, 123.1, 121.8, 120.9, 115.3; HRMS (ESI-
TOF) m/z [M + H]+ calcd for C11H9ClN3O 234.0429, found
234.0432.
N-(4-Nitrophenyl)benzamide (3s). The title compound was
synthesized using 4-nitrobenzenamine and 1-iodobenzene following
the general procedure. Eluent: EtOAc/hexane 20:80; yield: 126 mg,
N-(5-(4-Chlorobenzyl)-1,3,4-thiadiazol-2-yl)benzamide (3aa).
The title compound was synthesized using 5-(4-chlorobenzyl)-1,3,4-
thiadiazol-2-amine and 1-iodobenzene following the general proce-
dure. Eluent: EtOAc/hexane 20:80; yield: 96 mg, 66%; yellow solid;
1H NMR (400 MHz, DMSO-d6) δ 12.96 (s, 1H), 8.07 (d, J = 7.6 Hz,
2H), 7.63−7.66 (m, 1H), 7.52−7.56 (m, 2H), 7.38−7.43 (m, 3H),
4.40 (s, 2H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 163.8, 137.3,
133.5, 132.3, 131.3, 129.3, 129.2, 128.9, 34.7; HRMS (ESI-TOF) m/z
[M + H]+ calcd for C16H13ClN3OS 330.0462, found 330.0468.
N-(1-Methyl-1H-benzo[d]imidazol-2-yl)benzamide (3ab). The
title compound was synthesized using 1-methyl-1H-benzo[d]-
imidazol-2-amine and 1-iodobenzene following the general procedure.
1
72%; Pale yellow gummy mass; H NMR (400 MHz, DMSO-d6) δ
10.78 (s, 1H), 8.24 (d, J = 8.8 Hz, 2H), 8.05 (d, J = 8.8 Hz, 2H),
7.93−7.97 (m, 2H), 7.59−7.63 (m, 1H), 7.52−7.59(m, 2H); 13C{1H}
NMR (100 MHz, DMSO-d6) δ 166.7, 145.9, 142.9, 134.6, 132.6,
128.9, 128.3, 126.8, 125.1, 120.2, 112.8; HRMS (ESI-TOF) m/z [M
+ H]+ calcd for C13H11N2O3 243.0764, found 243.0758.
N-(3-Cyanopyridin-4-yl)benzamide (3t). The title compound was
synthesized using 4-aminopyridine-3-carbonitrile and 1-iodobenzene
following the general procedure. Eluent: EtOAc/hexane 30:70; yield:
116 mg, 66%; brown solid; 1H NMR (400 MHz, DMSO-d6) δ 11.28
(s, 1H), 8.84 (s, 1H), 8.36 (d, J = 8.8 Hz, 1H), 8.27−8.30 (m, 1H),
8.03 (d, J = 8.0 Hz, 2H), 7.59−7.63 (m, 1H), 7.49−7.53 (m, 2H);
13C{1H} NMR (100 MHz, DMSO-d6) δ 167.2, 155.5, 152.5, 142.4,
134.1, 132.9, 128.9, 128.8, 117.8, 114.5, 104.3; HRMS (ESI-TOF) m/
z [M + H]+ calcd for C13H10N3O 224.0818, found 224.0826.
N-(2-Methoxypyrimidin-4-yl)benzamide (3u). The title com-
pound was synthesized using 2-methoxypyrimidin-4-amine and 1-
iodobenzene following the general procedure. Eluent: EtOAc/hexane
1
Eluent: EtOAc/hexane 40:60; yield: 117 mg, 69%; brown solid; H
NMR (400 MHz, DMSO-d6) δ 12.72 (s, 1H), 8.25−8.27 (m, 2H),
7.46−7.53 (m, 5H), 7.19−7.23 (m, 2H), 3.71 (s, 3H); 13C{1H} NMR
(100 MHz, DMSO-d6) δ 174.1, 153.1, 138.7, 132.1,131.5, 130.6,
129.3, 128.4, 123.1, 112.5, 110.0, 40.8; HRMS (ESI-TOF) m/z [M +
H]+ calcd for C15H14N3O 252.1131, found 252.1143.
2-Methyl-N-(5-phenylpyridin-2-yl)benzamide (3ac). The title
compound was synthesized using 5-phenylpyridin-2-amine and 1-
bromo-2-methylbenzene following the general procedure. Eluent:
1
50:50; yield: 100 mg, 55%; off white solid; H NMR (400 MHz,
DMSO-d6) δ 11.1 (s, 1H), 8.47 (d, J = 5.6 Hz, 1H), 7.9 (d, J = 7.2 Hz,
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1
EtOAc/hexane 25:75; yield: 127 mg, 75%; an off white solid; H
NMR (400 MHz, DMSO-d6) δ 10.86 (s, 1H), 8.65 (d, J = 2.4 Hz,
1H); 8.28 (d, J = 8.0 Hz, 1H), 8.11−8.14 (m, 1H), 7.67−7.71 (m,
2H), 7.45−7.49 (m, 3H), 7.34−7.39 (m, 2H), 7.24−7.28 (m, 2H),
2.40 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 168.9, 151.8,
146.2, 137.2, 136.9, 136.5, 135.8, 131.9, 130.9, 130.3, 129.5, 128.1,
127.9, 127.0, 126.8, 126.1, 125.9, 114.8; HRMS (ESI-TOF) m/z [M
+ H]+ calcd for C19H17N2O 289.1335, found 289.1342.
Mysuru, Karnataka 570006, India; Email: rangappaks@
gmail.com
Authors
Srinivas Cheruku − Department of Studies in Chemistry,
Yuvaraja’s College, University of Mysore, Mysuru, Karnataka
570005, India
Ayyiliath M Sajith − Ortin laboratories Pvt., Ltd., Choutuppal
Mandal, Hyderabad, Telangana 508252, India
Yatheesh Narayana − Department of Studies in Chemistry,
Manasagangotri, University of Mysore, Mysuru, Karnataka
570006, India
Poornima Shetty − Department of Chemistry, Srinivas School
of Engineering, Mangalore, Karnataka 575001, India
Sandhya C Nagarakere − Department of Chemistry, St.
Philomena’s College, Mysuru, Karnataka 570015, India
Kunigal S Sagar − Department of Studies in Chemistry,
Manasagangotri, University of Mysore, Mysuru, Karnataka
570006, India
Kumara N Manikyanally − Department of Studies in
Chemistry, Yuvaraja’s College, University of Mysore, Mysuru,
Karnataka 570005, India
N - ( 5 - ( 4 - C h l o r o b e n z y l ) - 1 , 3 , 4 - t h i a d i a z o l - 2 - y l ) - 4 -
(trifluoromethoxy)benzamide (3ad). The title compound was
synthesized using 5-(4-chlorobenzyl)-1,3,4-thiadiazol-2-amine and 1-
iodo-4-(trifluoromethoxy)benzene following the general procedure.
1
Eluent: EtOAc/hexane 40:60; yield: 142 mg, 77%; yellow solid; H
NMR (400 MHz, DMSO-d6) δ 13.12 (s, 1H), 8.20 (d, J = 8.0 Hz,
2H), 7.53 (d, J = 8.0 Hz, 2H), 7.38−7.43 (m, 4H), 4.40 (s, 2H);
13C{1H} NMR (100 MHz, DMSO-d6) δ 151.9 137.3, 132.3, 131.4,
131.3, 129.2, 121.3, 34.7; HRMS (ESI-TOF) m/z [M + H]+ calcd for
C17H12ClF3N3O2S 414.0285, found 414.0286.
N-(5-(4-Isopropylphenyl)pyridin-2-yl)-1H-indole-5-carboxamide
(3ae). The title compound was synthesized using 5-(4-
isopropylphenyl)pyridin-2-amine and 5-bromo-1H-indole following
the general procedure. Eluent: EtOAc/hexane 20:80; yield: 108 mg,
1
65%; brown solid; H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H),
10.65 (s, 1H), 8.67 (s, 1H), 8.46 (s, 1H), 8.35- 8.37 (m, 1H), 8.07−
8.10 (m, 1H), 7.89−7.91 (m, 1H), 7.56−7.62 (m, 2H), 7.47−7.53
(m, 2H), 7.29−7.31 (m, 2H), 6.6 (s, 1H), 2.85−2.92 (m, 1H), 1.20
(d, J = 6.8 Hz, 6H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 167.5,
152.3, 148.4, 146.0, 138.5, 136.3, 135.0, 131.7, 127.7, 127.5, 127.4,
126.9, 125.5, 123.4, 114.9, 111.7, 103.0, 33.7, 24.3; HRMS (ESI-
TOF) m/z [M + H]+ calcd for C23H22N3O [M + H]+: 356.1757,
found 356.1761.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02999
Notes
The authors declare no competing financial interest.
N-(5-(4-Isopropylphenyl)pyridin-2-yl)benzamide (3af). The title
compound was synthesized using 5-(4-isopropylphenyl)pyridin-2-
amine and 1-iodobenzene following the general procedure. Eluent:
ACKNOWLEDGMENTS
■
1
K.M. acknowledges financial support from a VGST Project
(Grant No. Ksteps/VGST/GRD-681/KFIST(L1)/2018, dated
2018-08-27) and a PURSE grant (Grant No. PURSE/Phase 2/
27(C), dated: 2019-09-13 and PURSE/Phase 2/27(G), dated
2019-01-10) are gratefully acknowledged.
EtOAc/hexane 20:80; yield: 108 mg, 73%; off white solid; H NMR
(400 MHz, DMSO-d6) δ 10.87 (s, 1H), 8.69 (d, J = 2.0 Hz, 1H),
8.28- 8.30 (m, 1H), 8.06−8.13 (m, 3H), 7.58−7.65 (m, 3H), 7.50−
7.53 (m, 2H), 7.33−7.35 (m, 2H), 2.90−2.93 (m, 1H), 1.21 (d, J =
6.8 Hz, 6H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 166.5, 151.8,
148.6, 146.1, 136.4, 134.9, 132.5, 132.1, 128.9, 128.6, 127.6, 126.9,
115.1, 33.7, 24.3; HRMS (ESI-TOF) m/z [M + H]+ calcd for
C21H21N2O 317.1648, found 317.1640.
REFERENCES
■
(1) (a) Johansson, I. Amides, Fatty Acids. In Kirk-Othmer
Encyclopedia of Chemical Technology, 5th ed.; Kroschwitz, J. I., Ed.;
Wiley: Hoboken, NJ, 2004; Vol. 2, pp 442−463. (b) Roy, S.; Roy, S.;
Gribble, G. W. Metal-catalyzed amidation. Tetrahedron 2012, 68,
9867. (c) de Figueiredo, R. M.; Suppo, J. S.; Campagne, J. M.
Nonclassical routes for amide bond formation. Chem. Rev. 2016, 116
(19), 12029. (d) Roughley, S. D.; Jordan, A. M. The medicinal
chemist’s toolbox: an analysis of reactions used in the pursuit of drug
candidates. J. Med. Chem. 2011, 54 (10), 3451.
ASSOCIATED CONTENT
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sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02999.
Experimental procedures and NMR data for the
products (PDF)
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Accession Codes
CCDC 2062742 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
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AUTHOR INFORMATION
■
Corresponding Authors
Kempegowda Mantelingu − Department of Studies in
Chemistry, Manasagangotri, University of Mysore, Mysuru,
Karnataka 570006, India; orcid.org/0000-0003-1114-
8003; Email: kmlingu@gmail.com
Kanchugarkoppal Subbegowda Rangappa − Department of
Studies in Chemistry, Manasagangotri, University of Mysore,
5536
https://doi.org/10.1021/acs.joc.0c02999
J. Org. Chem. 2021, 86, 5530−5537

The Journal of Organic Chemistry
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