One-Pot Approach to N-Quinolyl 3′/4′-Biaryl Carboxamides by Microwave-Assisted Suzuki-Miyaura Coupling and N-Boc Deprotection

Article abstract of DOI:10.1021/acs.joc.6b01725

N-Quinolyl biaryl carboxamides have received tremendous attention for their notable biological properties. Here we have described a general protocol for the preparation of N-quinolyl 3′/4′-biaryl carboxamides by microwave-assisted Suzuki-Miyaura cross-coupling reaction and N-Boc deprotection in one pot. This method, which did not require acids, was used to produce a series of N-quinolyl 3′/4′-biaryl carboxamides with excellent functional group tolerance and high yields (70% to 95%).

Full text of DOI:10.1021/acs.joc.6b01725

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Article
One-Pot Approach to N-Quinolyl 3'/4'-Biaryl Carboxylamides by
Microwave-Assisted Suzuki-Miyaura Coupling and N-Boc Deprotection
Zhi-You Huang, Jing-Fang Yang, Ke Song, Qian Chen, Shao-Lin Zhou, Ge-Fei Hao, and Guang-Fu Yang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01725 • Publication Date (Web): 20 Sep 2016
Downloaded from http://pubs.acs.org on September 21, 2016
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OneꢀPot Approach to NꢀQuinolyl 3'/4'ꢀBiaryl Carboxylamides by
MicrowaveꢀAssisted SuzukiꢀMiyaura Coupling and NꢀBoc
Deprotection
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ZhiꢀYou Huang,a JingꢀFang Yang,a Ke Song,a Qian Chen,a ShaoꢀLin Zhou,a GeꢀFei
Hao,*,a and GuangꢀFu Yanga,b*
aKey Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry,
b
Central China Normal University, Wuhan 430079, P. R. China; Collaborative Innovation Center
of Chemical Science and Engineering, Tianjing 300072, P. R. China
Eꢀmail: gfyang@mail.ccnu.edu.cn, gfhao@mail.ccnu.edu.cn
Br
Boc
Ar
Boc
Ar
H
H2O
Pd(PPh3)4
ArB(OH)2
+
Microwave
T1, t1
Microwave
120 0C, 8 min
O
N
N
O
N
N
O
N
N
O
O
Pd(PPh3)4 (2 mol%)
N
N
H
+
ArB(OH)2
Y
Y
X
H2O (Deprotection)
Microwave
X
Boc
N
N
Br
Ar
X = O, S; Y = C, N
X = O, S; Y = C, N
1. One-pot
2. Water-promoted
3. 48 Examples, yields up to 95%
ABSTRACT: Nꢀquinolyl biaryl carboxylamides have received tremendous attention for their
notable biological properties. Here we have described a general protocol for the preparation of
Nꢀquinolyl 3'/4'ꢀbiaryl carboxylamides by microwaveꢀassisted SuzukiꢀMiyaura crossꢀcoupling
reaction and NꢀBoc deprotection in one pot. This method, which did not require acids, was used to
produce a series of Nꢀquinolyl 3'/4'ꢀbiaryl carboxylamides with excellent functional group
tolerance and high yields (70% to 95%).
Key words: Biaryl carboxylamides; Microwave irradiation; NꢀBoc deprotection; One pot;
SuzukiꢀMiyaura coupling
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Introduction
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The biaryl carboxylamides play important roles as vital building blocks in the synthesis of a
diversity of drugs such as anticancer,1ꢀ4 antiꢀinflammatory,5,6 anxiolytic,7 Alzheimer8 and anemia
therapeutic agents.9 Among these biaryl carboxylamides, Nꢀquinolyl(Q) 3'/4'ꢀbiaryl
carboxylamide is a unique substructure in medicinal chemistry, which have shown the potential
to antagonize bacterium,10 lose weight,11 promote differentiation of adult human cardiac
progenitor cells12 and activate TRPV1 (Transient Receptor Potential Vanilloid type 1) ion
channel.13,14
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Scheme 1. Selected methods to synthesize NꢀQ 3'/4'ꢀbiaryl carboxylamides
Although a variety of procedures are available for preparing Nꢀquinolyl(Q) 2'ꢀbiaryl
carboxylamides, methods available for the synthesis of NꢀQ 3'/4'ꢀbiaryl carboxylamides are still
limited. NꢀQ 3'/4'ꢀbiaryl carboxylamides are often synthesized starting from halogenꢀsubstituted
aromatic esters and aromatic boronic acids via three steps including SuzukiꢀMiyaura coupling,
ester hydrolysis and amide formation (Scheme 1, b) 13ꢀ15. However, these multiꢀstep processes
are usually time consuming and tedious procedures. Recently, Jana and Singh have reported an
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elegant example of preparing 2',4'ꢀdifluoroꢀNꢀ(quinolinꢀ8ꢀyl)ꢀ[1,1'ꢀbiphenyl]ꢀ4ꢀcarboxylamide
via the direct SuzukiꢀMiyaura crossꢀcoupling reaction of 4ꢀBromoꢀNꢀ(quinolinꢀ8ꢀyl) benzamide
and (2,4ꢀdifluorophenyl) boronic acid.16 But, this method requires a large amount of aromatic
boronic acids (2.0 equivalents). More importantly, the amide bearing a 8ꢀamioquinolinyl moiety
can strongly chelate the palladium catalyst, which may poison the catalyst and result in the high
loading of catalyst. Thus, it is still desirable to develop low cost protocols for the synthesis of
NꢀQ 3'/4'ꢀbiaryl carboxylamides. Moreover, during the course of our study on preparing
Nꢀ(pyridinꢀ2ꢀylmethyl) biphenylꢀ4ꢀsulfonamides,17 we found that the NꢀBoc protection material
could be easily prepared in higher yields. Further, the oneꢀpot method is less time consuming and
gives a higher yield than the stepꢀwise approach. Hence, one pot method draws much attention of
chemists.18 Herein, we reported oneꢀpot microwaveꢀassisted SuzukiꢀMiyaura crossꢀcoupling and
NꢀBoc deprotection approach to prepare a variety of NꢀQ 3'/4'ꢀbiaryl carboxylamides with
excellent functional group tolerance and high yields.
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Although, the palladiumꢀcatalyzed SuzukiꢀMiyaura reactions were found to be the most
approaches to synthesize biaryl carboxylamides,19 the direct SuzukiꢀMiyaura coupling to
Nꢀ8ꢀquinoly 3'/4'ꢀbiaryl carboxylamides consumes more time and wasted 1.0 equivalent boronic
acid. So, it is obvious that the catalyst could be inactivated by the Nꢀ8ꢀquinoly at some extent.15,
19e, 20 Thus, it is benificial to prevent the Nꢀ8ꢀquinoly group from chelating the catalyst in order to
facilitate the economic conversion of starting materials. Even more important, in our continuous
efforts on the application of microwave irradiation in the targetꢀoriented synthesis,21 our present
aim is to develop a oneꢀpot strategy towards NꢀQ 3'/4'ꢀbiaryl carboxylamides via sequential
Pd(PPh3)4ꢀcatalyzed SuzukiꢀMiyaura coupling and waterꢀpromoted NꢀBoc deprotection under
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microwave irradiation.
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RESULTS AND DISSCUSSION
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Although the conditions of coupling and the deprotection of amide NꢀBoc are known
separately,22 it is still a big challenge to find the optimum conditions able to perform
SuzukiꢀMiyaura coupling and amide NꢀBoc deprotection sequentially in a oneꢀpot manner under
the microwave irradiation. For our initial studies, the reaction of bromide 3a with 1.0 equivalent
phenyl boronic aicd 4a in the presence of Pd(PPh3)4 and NaOAc under microwave irradiation
was chosen as a benchmark reaction (Table 1. The optimization of amide NꢀBoc deprotecting see
Support Information Table S1). To our delight, 78 % of coupling and deprotecting product (5aa)
was obtained with a temperature of 80 °C in 6 minutes (Table 1, entry 1). Process monitoring
indicated that 3a could not be completely converted into the SuzukiꢀMiyaura coupling product
5b. But, the deprotection of the 5b and the remaining 3a was smooth. Therefore, in order to
improve the yield of 5aa, the reaction time was prolonged to promote the first step
SuzukiꢀMiyaura coupling overwhelmingly. So, the desired product 5aa was obtained in the same
yield of 94% in 8 minutes and 10 minutes (entry 2, 3). However, the yield of 5aa was reduced to
84% with a temperature of 85 °C (entry 4). Also, the different solvents were screened, such as
water mixed with dioxane, DME, DMF, 2ꢀMe THF and isopropanol (entry 2, 5–8). The mixture
of water and dioxane (v/v = 1 : 3) was proved to produce the best results. Subsequently, the
effect of bases on this reaction was explored, and among these bases (NaOAc, Na2CO3, K3PO4
and Cs2CO3), NaOAc was identified as the best one (entry 2, 9–11). In addition, we noted that in
the absence of base (entry 12) or catalyst (entry 15) the coupling reaction would not take place,
but the deprotection was not affected. Finally, the effect of palladium loading was invested. We
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found that decreasing the loading of catalyst to 1.5 mol % (entry 13) and 1.0 mol % (entry 14)
gave a 87% and 81%
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Table 1. Optimization of Pd(PPh3)4ꢀCatalyzed SuzukiꢀMiyaura Coupling and
WaterꢀPromoted NꢀBoc Deprotecting Oneꢀpot reactiona,b
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T1 (℃),
T2(℃),
Entr
y
Organic
Solvent
Catalyst
Yield
Yield
Yield
Base
(x mol %) t1 ( min ) t2( min ) (5aa %) (5b %) (3aa %)
1
2
Dioxane
Dioxane
Dioxane
Dioxane
DME
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
Na2CO3
K3PO3
Cs2CO3
ꢀꢀ
2
2
80, 6
80, 8
80, 10
85, 8
80, 8
80, 8
80, 8
80, 8
80, 8
80, 8
80, 8
80, 8
80, 8
80, 8
80, 8
80, 8
80, 8
80, 120
120, 8
120, 8
120, 8
120, 8
120, 8
120, 8
120, 8
120, 8
120, 8
120, 8
120, 8
120, 8
120, 8
120, 8
120, 8
120, 8
120, 8
78
94
94
84
91
86
35
51
86
81
77
0
0
<1
<1
0
18
<1
<1
14
<5
<5
21
46
11
15
18
95
<5
14
95
94
88
<5
3
2
4
2
5
2
0
6
DMF
2
0
7
2ꢀMe THF
isopropanol
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
2
41
0
8
2
9
2
0
10
11
12
13
14
15
16c
17c
18d
2
0
2
0
2
0
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
1.5
1.0
ꢀꢀ
2
89
81
0
0
0
0
< 5
9
0
10
2
0
Reflux,
600
22
71
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a Reactions conditons: 1) 3a (0.2 mmol), 4a (0.2 mmol), catalyst was Pd(PPh3)4, base (0.4 mmol), solvent 4 mL
(3 mL organic solvent and 1 mL H2O); 2) under N2. b Isolated yield. c Catalyst was Pd/C (10%) d Conventional
heating.
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Table 2. Scope of 3aꢀ3c and (hetero)arylboronic acid (4)a,b
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O
O
O
O
N
H
N
H
N
H
N
H
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
6
H3C
tBu
O
5aa, 94 %
t1=8 min
5ab, 94 %
t1=8 min
5ac, 95 %
t1=9 min
5ad, 94 %
t1=8 min
7
8
9
O
O
O
O
N
H
N
H
N
H
N
H
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F
F
Cl
5ae, 95 %
t1=10 min
5af, 92 %
t1=10 min
5ag, 90 %
t1=15 min
5ah, 93 %
t1=9 min
F
O
O
O
O
N
H
N
H
N
H
N
H
O
HO
F3CO
F3C
5ai, 87 %
t1=9 min
5aj, 91 %
t1=12 min
5ak, 86 %
t1=25 min
5al, 90 %
t1=20 min
O
O
O
O
N
H
N
H
N
H
N
H
Cl
O
Cl
Cl
Cl
5am, 87 %
t1=25 min
5an, 89 %
t1=25 min
5ao, 90 %
t1=25 min
5ap, 88 %
t1=25 min
O
Cl
Cl
O
O
O
N
H
N
H
N
H
O
N
N
H
N
O
5aq, 88 %
t1=15 min
5ar, 89 %
t1=15 min
5as, 85 %
t1=25 min
5ba, 95 %
t1=10 min
tBu
O
F
Cl
O
O
O
O
N
H
N
H
N
H
N
H
N
N
N
N
5bd, 93 %
t1=15 min
5be, 93 %
t1=15 min
5bb, 95 %
t1=10 min
5bc, 94 %
t1=10 min
O
F3C
Cl
O
O
N
O
O
O
N
H
N
H
N
H
N
H
N
Cl
N
N
N
5bg, 85 %
t1=25 min
5bh, 88 %
t1=20 min
5bi, 87 %
t1=15 min
5bf, 85 %
t1=30 min
O
O
O
O
N
H
N
H
N
H
N
H
N
N
N
N
N
O
F
5ca, 94 %
t1=10 min
5cb, 94 %
t1=10 min
5cc, 93 %
t1=10 min
5cd, 84 %
t1=20 min
a Reactions conditons:3aꢀ3c (0.2 mmol), 4 (0.2 mmol), Pd(PPh3)4 (2 mol%), NaOAc (0.4 mmol), Dioxane:H2O =
3 mL:1 mL , T2=120 °C, t2=8 min, protected by N2. b Isolated yield.
yield of 5aa, respectively. While, a little bit of 5aa was obtained when used 2.0 mol % and 10
mol % of Pd/C (entry 16ꢀ17). Compared with conventional heating (entry 18), microwave
irradiation could significantly accelerate the reaction and notably improve the yield of the
product. As a result, the combination of 2.0 mol % Pd(PPh3)4, 1.0 equivalent phenylboronic acid
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and 2.0 equivalents NaOAc in dioxane mixed water with a temperature of 80 °C in 8 minutes for
the first step and then enhancing the reaction temperature to 120 °C in 8 minutes for the second
step was fixed, as optimal conditions.
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Once the optimized reaction conditions were identified, the scope and limitations of this
oneꢀpot process were explored. A variety of aromatic boronic acids and bromineꢀsustituted NꢀQ
arylamides were applied. Various substituted (hetero)arylboronic acids were determined, the
results were shown in Table 2. The reactions between 3a and (hetero)arylboronic acids (4)
always went smoothly. Both electronꢀwithdrawing and electronꢀdonating groups, such as
methoxycarbonyl (5am), trifluoromethyl (5ak) and methyl (5ab), tertꢀbutyl (5ac), methoxy
(5ad), halogen (5aeꢀ5ah), trifluoromethoxy (5aj) afforded the desired products in good to
excellent yields. More importantly, the reaction was proved to be well tolerant of valuable but
unstable groups, such as hydroxyl (5ai) and acetyl (5al). In addition, disubstituted and
heteroꢀarylboronic acids were also investigated and afforded the corresponding products
(5anꢀ5as). To increase the scope of our oneꢀpot reaction, the 3b and (hetero)arylboronic acids (4)
was tested. Very similar results were obtained in the presence of metaꢀsubstituent NꢀQ
benzamide (3b). The reaction of phenylboronic aid gave 5ba in 95% yields. The reaction of
electronꢀrich phenylboronic acid, 4ꢀtertꢀbutyl and 4ꢀmethoxy, led to 5bb and 5bc in 95% and
94% yield, respectively. The halogen substituted phenylboronic acids (5bdꢀ5be) could also give
excellent yield. Even the electronꢀ
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Figure 1. Ortep diagrams of 5ba (the thermal ellipsoids are drawn at the 50% probability level).
deficient phenylboronic acid, such as methoxycarbonyl and trifluoromethyl groups were found to
be suitable partner of oneꢀpot reaction and gave 5bf and 5bg in a good yields. Of note, the
2,4ꢀdichloro substituted phenylboronic and 4ꢀpyridinylboronic acid could be successfully
converted to the product (5bhꢀ5bi). Then, several reactions using 3c as the starting materials
were performed. The target products 5caꢀ5cd were obtained in 84ꢀ94% yields using 2.0 mol % of
Table 3. Scope of 3dꢀ3f and (hetero) arylboronic acid (4)a,b
O
O
1). Pd(PPh3)4 (2 mol%)
2). H2O (Deprotection)
+
ArB(OH)2
4
N
N
H
Y
Y
X
Boc
N
X
N
Br
Ar
Microwave
One pot
3d-3f
6
X = O, S; Y = C, N
X = O, S; Y = C, N
O
N
O
N
O
N
O
S
S
H
N
O
S
S
H
N
O
H
N
6aa, 92 %
t1=10 min
6ab, 91 %
t1=15 min
6ac, 83 %
t1=25 min
N
N
N
F
O
O
O
N
H
N
H
N
H
N
N
S
N
6ad, 76 %
t1=10 min
6ae, 76 %
t1=15 min
6af, 71 %
t1=30 min
F
O
O
O
N
H
N
H
N
H
N
N
N
N
N
S
N
6ag, 75 %
t1=10 min
6ah, 73 %
t1=15 min
6ai, 70 %
t1=30 min
F
a Reactions conditons:3dꢀ3f (0.2 mmol), 4 (0.2 mmol), Pd(PPh3)4 (2 mol %), NaOAc (0.4 mmol),
Dioxane:H2O = 3 mL:1 mL , T2=120 °C, t2=8 min, protected by N2. b Isolated yield.
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Table 4. Scope of 3g and (hetero)arylboronic acid (4)a,b
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a Reactions conditons:3g (0.2 mmol), 4 (0.2 mmol), Pd(PPh3)4 (2 mol %), NaOAc (0.4 mmol), Dioxane:H2O = 3
mL:1 mL , T2=120 °C, t2=8 min, protected by N2. b Isolated yield.
Pd(PPh3)4 as the catalyst under the microwave irradiation. Furthermore, the structure of 5ba was
confirmed by Xꢀray data, and it showed that the phenyl group was at the metaꢀposition (Figure
1).
Notably, the oneꢀpot reaction was not limitation to the use of NꢀQ fiveꢀmembered heteroaryl
carboxylamides. The reaction of (hetero)arylboronic acids(4) with 3dꢀ3f (Containing furanyl,
thiophenyl, thiazolyl, respectively) were also produced the desired products 6 in good to
excellent yield (Table 3). It was obvious that the 3d could give more corresponding products than
3e and 3f.
To further examine the oneꢀpot reaction and rapidly expand our unique compound
collection, we also carried out the reaction between 3g and (hetero)arylboronic acids (4).
Accordingly, the target oriented productsꢀbiaryl carboxylamide pyrabactin (Py) analogues as
abscisic acid (ABA) agonists (7aaꢀ7ag) were obtained in 86ꢀ95% yield (Table 4). The analogue
7aa has been found to be active on the ABA receptor PYR1 via a further molecular simulation
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study (Figure 2). The pyridine ring can form conservative πꢀπ stacking interaction with residue
Y126 (Fig. 2B). The amide group can not only form hydrogen bond with residue E100, but also
form another hydrogen
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Table 5. Binding Free Energies ( kcal/mol) Calculated for the PYR1 with ABA, Py and 7aa
ꢀTΔS
ΔGbind
ꢁEele
ꢁEVDW
ꢁEMM
ꢁ
Gsol
ꢁEbind
ꢀ38.14
ꢀ34.96
ꢀ54.59
ꢀ40.45
ꢀ45.13
ꢀ40.35
ꢀ78.59
ꢀ80.09
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70.42
ꢀ20.56
ꢀ22.56
ꢀ24.53
16.22
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20.11
ꢀ4.34
ꢀ7.12
ꢀ4.42
ABA
Py
7aa
Figure 2. Computational modeling of Py (A) and 7aa (B) in PYR1 (PDB code: 3QN1)
bond with residue K65 to stabilize the binding mode. However, the biphenyl group makes 7aa
bind with P94 much more closely than bromine atom. As shown in Table 5, the estimated
binding free energy of 7aa is ꢀ4.42 kcal/mol which is nearly equal to that of ABA (ꢀ4.34
kcal/mol), but lower than that of pyrabactin (ꢀ7.12 kcal/mol).
The molecular mechanics PoissonꢀBoltzmann surface area (MMꢀPBSA) method in the
AMBER12 package was employed to perform the free energy analyses. The overall objective of
the MMꢀPBSA method is to calculate the free energy difference between two states which most
often represent the bound and unbound state of two solvated molecules. The free energy of the
ligand binding with the receptor, ꢁGbind, is calculated from the difference between the free energy
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of the receptorꢀligand complex (Gcomplex) and the sum of the free energies of the unbound
receptor (Greceptor) and ligand (Gligand) as the following Equation 1.
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ꢁGbind = Gcomplex − (Gligand + Greceptor
)
(1)
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The binding free energy ꢁGbind includes three items: MM gasꢀphase binding energy (ꢁEMM),
solvation free energy (ꢁGsol), and entropy contribution (ꢀTꢁS). The sum of molecular
mechanical gasꢀphase binding energy (ꢁEMM) and solvation free energy (ꢁGsol) is denoted by
binding energy (ꢁEbind). The ꢁGbind was estimated from ꢁEbind and ꢀT∆S in Equation 2. The
ꢁEbind is calculated from ꢁEMM and ꢁGsol in Equation 3.
ꢁGbind =ꢁEbind − TꢁS
ꢁEbind =ꢁEMM + ꢁGsol
(2)
(3)
The ꢁEMM is calculated by Equation 4, where ꢁEele and ꢁEVDW represent the electrostatic
and van der Waals interactions. The solvation free energy ꢁGsol consists of two parts: the
electrostatic contribution to the solvation free energy (ꢁGPB) and nonelectrostatic contribution to
the solvation free energy (ꢁGnp) as described in Equation 5 .
ꢁEMM =ꢁEele + ꢁEVDW
ꢁGsol = ꢁGPB + ꢁGnp
∆S = ∆Sconf + ∆Ssol
(4)
(5)
(6)
The ꢁSsol and ꢁSconf are the solvation entropy and the conformational entropy change in the
Equation 6. In the binding process, the conformational entropy change is related with the change
of the number of rotatable bonds during the binding process, the solvation entropy is related to
the tendency of water molecules to minimize their contacts with hydrophobic groups in protein.
When an empirical solvation model is developed, one calculates the parameters against available
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experimental data without accounting for the detailed structural information, which means to
average the overall solvation contributions from both solvent and solute. Therefore, the
computational procedure is used to evaluate the entropic contribution (ꢀTꢁS) to the binding free
energy was the same as our previous publication.23
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ꢀT∆Sconf= w (ꢁNrot)
The contribution to the binding free energy from the conformational entropy change is
proportional to the number (ꢁNrot) of the lost rotatable bonds during the binding in which is
the scaling factor(Equation 7). This adjustable parameter( ) was calibrated to be 1 kcal/mol here
for the PYR1 proteins. We note that the value of 1 kcal/mol used in the present study is the
same as that used previously by other researchers.24 The adjustment of the
value usually does
(7)
w
w
w
w
not change the qualitative order of the calculated binding free energies calculated for a series of
compounds binding with a given type of protein.25
CONCLUSION
In summary, a oneꢀpot microwaveꢀassisted SuzukiꢀMiyaura crossꢀcoupling reaction and NꢀBoc
deprotection for preparing a variety of NꢀQ 3'/4'ꢀbiaryl carboxylamides was developed. A series
of NꢀQ biaryl carboxylamides was obtained in good to excellent yields. In addition, the broad
substrate scopes and excellent reactivity make the strategy operationally concise and facilitate
rapid library construction of potential pyrabactin analogues as abscisic acid analogs.
EXPERIMENTAL SECTION
General Information. All reagents and solvents were obtained commercially except when
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otherwise noted. Thinꢀlayer chromatography (TLC) analysis was used to monitor reaction which
was carried out on silica plates. Flash column chromatography was performed using silica
gel(200ꢀ300 mesh).1H spectra were recorded in CDCl3 or DMSOꢀd6 on 400 or 600 MHz NMR
spectrometers and resonances (•) are given in parts per million relative to tetramethylsilane. Data
are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m =
multiplet, q = quarternary), coupling constants (Hz) and integration. 13C spectra were recorded in
CDCl3 or DMSOꢀd6 on 100 or 150 MHz NMR spectrometers and resonances (•) are given in
ppm. High resolution mass spectra (HRMS) were analyzed by a TOF analyzer. Microwave
irradiation reactions were carried out on a Smith synthesizerTM instrument (The temperature of
reaction system was controlled by the wall infrared sensor. While, the pressure was regulated by
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1
the nonꢀinvasive pressure sensor). All products reported showed H and 13C NMR spectra in
agreement with the assigned structures.
General Procedure for the Synthesis of Compounds 3aꢀ3g. The synthesis of 3aaꢀ3ag
is representative: 2 (amino, 10 mmol) and DMAP (3 mmol) were placed in a 100 mL twoꢀnecked
reaction flask, and the flask was flushed with nitrogen. Dichloromethane (40 mL), triethylamine
(12 mmol), and 1 (acid, 11 mmol) were added, and the mixture was stirred at room temperature
for 18 h. The resulting mixture was then quenched with water. The mixture was extracted with
dichloromethane, and the combined organic layer was dried over sodium sulfate. Concentration
in vacuum followed by silica gel column purification (petroleum ether / acetone = 20:2) gave
3aaꢀ3ag.26ꢀ28
The synthesis of 3aꢀ3g is representative: Bocꢀanhydride (6 mmol) was added to a solution
of 3aaꢀ3ag (3 mmol) and DMAP (4.5 mmol) in CH2Cl2 (40 mL) and the reaction mixture was
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stirred overnight. The reaction mixture was quenched with sat. aq NH4Cl (40 mL) and extracted
with CH2Cl2 (3 x 40 mL). The combined organic extracts were dried (Na2SO4), concentrated
under reduced pressure and purified by column chromatography (petroleum ether / acetone =
20:2, Rf = 0.15) to give the 3aꢀ3g.29ꢀ31
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Typical Pd(PPh3)4ꢀCatalyzed and WaterꢀPromoted OneꢀPot Strategy to NꢀQ
Biaryl Carboxamides (5ꢀ7). 3 (0.2 mmol) and arylboronic acids (4, 0.2 mmol) were
dissolved in dioxane (3 mL) and H2O (1 mL) in a microwave tube under a nitrogen atmosphere.
Pd(PPh3)4 (2 mol% , 4.6 mg) and sodium acetate (0.4 mmol) were added, the reaction mixture was
irradiated in a microwave apparatus at 80 ℃ for 8ꢀ30 min. Then, the temperature was increased
to 120 ℃ for another 8 min. After the reaction mixture was cooled to ambient temperature, the
product was concentrated, and the crude mixture was purified by column chromatography on
silica gel (petroleum ether/acetone = 20:1.5) to the desired product.
4-bromo-1-(quinolin-8-yl)benzamide (3aa). White solid (petroleum ether / acetone = 20:1, Rf =
0.15); 3.043g, yield 93%; mp 128 ꢀ 129 °C.32 1H NMR (600 MHz, DMSO) δ 10.67 (s, 1H), 8.99
(dd, J = 4.2, 1.2 Hz, 1H), 8.71 (d, J = 7.8 Hz, 1H), 8.47 (dd, J = 8.4, 1.2 Hz, 1H), 7.99 (d, J = 8.4
Hz, 2H), 7.84 (d, J = 8.4 Hz, 2H), 7.77 (d, J = 8.2 Hz, 1H), 7.71 – 7.65 (m, 2H). 13C NMR (150
MHz, DMSO) δ 163.5, 149.1, 138.2, 136.6, 133.8, 133.4, 131.9, 129.1, 127.7, 126.9, 125.9, 122.4,
122.2, 116.7. HRMS (ESI): m/z [M+H]+ calcd for C16H12BrN2O 327.0133 ; found 327.0121.
3-bromo-1-(quinolin-8-yl)benzamide(3ab). White solid (petroleum ether / acetone = 20:1, Rf =
0.15); 3.01 g, yield 92%; mp 99 ꢀ 100 °C.33 1H NMR (600 MHz, DMSO) δ 10.71 (s, 1H), 9.04 (s,
1H), 8.72 (d, J = 7.8 Hz, 1H), 8.52 (d, J = 8.4 Hz, 1H), 8.24 (s, 1H), 8.09 (d, J = 7.2 Hz, 1H),
7.93 (d, J = 7.8 Hz, 1H), 7.83 (d, J = 7.8 Hz, 1H), 7.76 – 7.70 (m, 2H), 7.65 (t, J = 7.8 Hz, 1H).
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13C NMR (150 MHz, DMSO) δ 163.0, 149.1, 138.4, 136.7, 136.6, 134.7, 133.7, 131.0, 130.0,
127.8, 126.9, 125.9, 122.7, 122.3, 122.2, 117.2. HRMS (ESI): m/z [M+H]+ calcd for
C16H12BrN2O 327.0133 ; found 327.0123.
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4-bromo-1-(quinolin-8-yl)-1-naphthamide(3ac). White solid (petroleum ether / acetone = 20:1, Rf
= 0.15); 3.395 g, yield 90%; mp 198 ꢀ 199 °C. 1H NMR (600 MHz, CDCl3) δ 10.41 (s, 1H), 9.04
(s, 1H), 8.76 (s, 1H), 8.54 (s, 1H), 8.36 (d, J = 7.8 Hz, 1H), 8.23 (s, 1H), 7.91 (s, 1H), 7.78 (s,
1H), 7.65 (m, 4H), 7.49 (s, 1H). 13C NMR (150 MHz, CDCl3) δ 166.9, 148.3, 138.3, 136.4, 134.4,
134.3, 132.1, 131.2, 129.0, 128.0, 127.8, 127.4, 127.3, 126.0, 125.9, 125.5, 122.2, 121.7, 116.9.
HRMS (ESI): m/z [M+H]+ calcd for C20H14BrN2O 377.0290 ; found 377.0278.
5-bromo-1-(quinolin-8-yl)furan-2-carboxamide (3ad). White solid (petroleum ether / acetone =
20:1, Rf = 0.15); 2.601 g, yield 82%; mp 109 ꢀ 110 °C.33 1H NMR (600 MHz, DMSO) δ 10.54 (s,
1H), 9.02 (dd, J = 4.2, 1.2 Hz, 1H), 8.68 (d, J = 7.8 Hz, 1H), 8.48 (dd, J = 8.4, 1.2 Hz, 1H), 7.76
(d, J = 8.4 Hz, 1H), 7.70 (dd, J = 8.4, 4.2 Hz, 1H), 7.65 (t, J = 7.8 Hz, 1H), 7.43 (d, J = 3.6 Hz,
1H), 6.94 (d, J = 3.6 Hz, 1H). 13C NMR (150 MHz, DMSO) δ 154.3, 149.3, 149.1, 137.8, 136.8,
133.3, 127.8, 127.0, 125.6, 122.5, 122.4, 118.0, 116.4, 115.1. HRMS (ESI): m/z [M+H]+ calcd
for C14H10BrN2O2 316.9926 ; found 316.9915.
5-bromo-N-(quinolin-8-yl)thiophene-2-carboxamide (3ae). White solid (petroleum ether /
acetone = 20:1, Rf = 0.15); 2.699 g, yield 81 %; mp 156 ꢀ 157 °C.35 1H NMR (600 MHz, DMSO)
δ 10.58 (s, 1H), 9.00 (d, J = 4.2 Hz, 1H), 8.50 (d, J = 7.8 Hz, 2H), 7.90 (d, J = 4.2 Hz, 1H), 7.80
(d, J = 8.4 Hz, 1H), 7.70 (dd, J = 8.4, 4.2 Hz, 1H), 7.66 (t, J = 7.8 Hz, 1H), 7.43 (d, J = 4.2 Hz,
1H). 13C NMR (150 MHz, CDCl3) δ 159.0, 147.7, 141.2, 137.6, 137.4, 133.4, 130.9, 128.8,
128.1, 127.7, 122.2, 121.6, 119.0, 118.0. HRMS (ESI): m/z [M+H]+ calcd for C14H10BrN2OS
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332.9697 ; found 332.9665.
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5-bromo-N-(quinolin-8-yl)thiazole-2-carboxamide (3af). White solid (petroleum ether / acetone
= 20:3, Rf = 0.15); 2.707 g, yield 81 %; mp 137 ꢀ 138 °C. 1H NMR (600 MHz, CDCl3) δ 10.55
(s, 1H), 8.87 (d, J = 4.2. Hz, 1H), 8.79 – 8.72 (m, 1H), 8.22 (d, J = 8.4 Hz, 2H), 7.61 – 7.56 (m,
2H), 7.52 (dd, J = 8.4, 4.2 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 157.2, 156.0, 148.5, 141.3,
138.1, 137.9, 136.4, 133.4, 127.8, 127.2, 122.4, 121.9, 116.7. HRMS (ESI): m/z [M+H]+ calcd
for C13H9BrN3OS 333.9650 ; found 333.9641.
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4-bromo-N-(pyridin-2-ylmethyl)benzamide (3ag). White solid (petroleum ether / acetone = 20:1,
Rf = 0.15); 2.737 g, yield 94%; mp 112ꢀ113 °C.36 1H NMR (600 MHz, CDCl3) δ 8.57 (d, J = 4.2
Hz, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.72 (m, 2H), 7.59 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 7.8 Hz,
1H), 7.25 (s, 1H), 4.76 (d, J = 4.8 Hz, 2H). 13C NMR (150 MHz, DMSO) δ 165.5, 158.6, 148.9,
136.7, 133.3, 131.4, 129.4, 125.1, 122.1, 121.0, 44.8. HRMS (ESI): m/z [M+H]+ calcd for
C13H12BrN2O 291.0133 ; found 291.0146.
tert-butyl (4-bromobenzoyl)(quinolin-8-yl)carbamate (3a). White solid (petroleum ether / acetone
= 20:1, Rf = 0.15); 1.180 g, yield 92%; mp 159 ꢀ 160 °C. 1H NMR (600 MHz, DMSO) δ 8.90 (d,
J = 4.2 Hz, 1H), 8.47 (d, J = 8.4 Hz, 1H), 8.06 (d, J = 8.4 Hz, 1H), 7.82 (d, J = 7.2 Hz, 1H), 7.76
(s, 4H), 7.68 (t, J = 7.8 Hz, 1H), 7.61 (dd, J = 8.4, 4.2 Hz, 1H), 1.14 (s, 9H). 13C NMR (150 MHz,
DMSO) δ 171.7, 152.4, 150.7, 143.3, 136.5, 136.2, 131.3, 130.0, 129.3, 128.6, 128.5, 126.4, 125.0,
122.0, 82.7, 27.0. HRMS (ESI): m/z [M+H]+ calcd for C21H20BrN2O3 427.0657 ; found 427.0630.
tert-butyl (3-bromobenzoyl)(quinolin-8-yl)carbamate(3b). White solid (petroleum ether / acetone
1
= 20:1, Rf = 0.15); 1.154 g, yield 90 %; mp 125 ꢀ 126 °C. H NMR (600 MHz, DMSO) δ 8.91
(d, J = 3.0 Hz, 1H), 8.48 (d, J = 7.8 Hz, 1H), 8.07 (d, J = 7.8 Hz, 1H), 8.00 (s, 1H), 7.86 (d, J =
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7.2 Hz, 1H), 7.80 (m, 2H), 7.69 (t, J = 7.8 Hz, 1H), 7.61 (dd, J = 8.4, 4.2 Hz, 1H), 7.51 (t, J = 7.8
Hz, 1H), 1.14 (s, 9H). 13C NMR (150 MHz, DMSO) δ 171.1, 152.3, 150.8, 143.3, 139.3, 136.5,
136.3, 134.0, 130.6, 130.4, 129.5, 128.7, 128.6, 126.8, 126.4, 122.1, 121.3, 82.9, 27.0. HRMS
(ESI): m/z [M+H]+ calcd for C21H20BrN2O3 427.0657 ; found 427.0635.
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tert-butyl (4-bromo-1-naphthoyl)(quinolin-8-yl)carbamate (3c). White solid (petroleum ether /
acetone = 20:1, Rf = 0.15); 1.289 g, yield 90%; mp 159 ꢀ 160 °C. 1H NMR (600 MHz, CDCl3) δ
9.00 (s, 1H), 8.65 (s, 1H), 8.33 (s, 1H), 8.24 (d, J = 7.8 Hz, 1H), 7.95 (s, 1H), 7.91 (d, J = 7.8 Hz,
1H), 7.86 (d, J = 7.8 Hz, 1H), 7.80 (d, J = 7.2 Hz, 1H), 7.65 (d, J = 6.6 Hz, 4H), 7.48 (s, 1H),
0.90 (s, 9H). 13C NMR (150 MHz, CDCl3) δ 171.8, 152.6, 150.5, 136.3, 131.8, 131.6, 129.3,
129.2, 128.9, 128.6, 127.8, 127.7, 127.4, 126.3, 126.2, 125.4, 125.0, 121.7, 83.5, 27.1. HRMS
(ESI): m/z [M+H]+ calcd for C25H22BrN2O3 477.0814 ; found 477.0800.
tert-butyl (5-bromofuran-2-carbonyl)(quinolin-8-yl)carbamate (3d). White solid (petroleum
1
ether / acetone = 20:1, Rf = 0.15); 1.089 g, yield 87%; mp 111 ꢀ 112 °C. H NMR (600 MHz,
DMSO) δ 8.88 (s, 1H), 8.47 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 8.4 Hz, 1H), 7.75 (d, J = 7.2 Hz,
1H), 7.66 (t, J = 7.8 Hz, 1H), 7.60 (dd, J = 8.4, 4.2 Hz, 1H), 7.25 (d, J = 3.0 Hz, 1H), 6.90 (d, J =
3.0 Hz, 1H), 1.32 (s, 9H). 13C NMR (150 MHz, DMSO) δ 162.4, 155.0, 151.9, 150.9, 145.8,
143.2, 136.5, 135.8, 135.7, 129.4, 129.1, 128.6, 126.4, 122.2, 83.4, 27.2. HRMS (ESI): m/z
[M+H]+ calcd for C19H18BrN2O4 417.0450 ; found 417.0461.
tert-butyl (5-bromothiophene-2-carbonyl)(quinolin-8-yl)carbamate (3e). White solid (petroleum
ether / acetone = 20:1, Rf = 0.15); 1.118 g, yield 86%; mp 92 ꢀ 93 °C. 1H NMR (600 MHz,
DMSO) δ 8.91 (d, J = 4.2 Hz, 1H), 8.47 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 8.4 Hz, 1H), 7.77 (d, J =
7.2 Hz, 1H), 7.66 (t, J = 7.8 Hz, 1H), 7.61 (dd, J = 8.4, 4.2 Hz, 1H), 7.39 (d, J = 4.2 Hz, 1H),
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7.28 (d, J = 4.2 Hz, 1H), 1.26 (s, 9H). 13C NMR (150 MHz, CDCl3) δ 164.4, 153.0, 150.4, 143.9,
140.4, 136.8, 136.1, 133.1, 130.0, 129.0, 128.9, 128.4, 126.2, 121.7, 119.9, 83.4, 27.6. HRMS
(ESI): m/z [M+H]+ calcd for C19H18BrN2O3S 433.0222 ; found 433.0211.
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tert-butyl (5-bromothiazole-2-carbonyl)(quinolin-8-yl)carbamate (3f). White solid (petroleum
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ether / acetone = 20:3, Rf = 0.15); 1.081 g, yield 83%; mp 111ꢀ112 °C. H NMR (600 MHz,
DMSO) δ 8.92 (d, J = 4.2 Hz, 1H), 8.49 (d, J = 8.4 Hz, 1H), 8.15 (s, 1H), 8.09 (d, J = 8.4 Hz,
1H), 7.86 (d, J = 7.2 Hz, 1H), 7.69 (t, J = 7.8 Hz, 1H), 7.63 (dd, J = 8.4, 4.2 Hz, 1H), 1.26 (s,
9H). 13C NMR (150 MHz, DMSO) δ 162.3, 155.0, 151.9, 150.9, 145.8, 143.2, 136.5, 135.8,
135.7, 129.4, 129.1, 128.6, 126.4, 122.2, 83.3, 27.2. HRMS (ESI): m/z [M+H]+ calcd for
C18H17BrN3O3S 434.0174 ; found 434.0135.
tert-butyl (4-bromobenzoyl)(pyridin-2-ylmethyl)carbamate (3g). White solid (petroleum ether /
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acetone = 20:1, Rf = 0.15); 1.080 g, yield 92%; mp 82ꢀ83 °C. H NMR (600 MHz, DMSO) δ
8.50 (d, J = 4.8 Hz, 1H), 7.79 (t, J = 7.8 Hz, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.4 Hz,
2H), 7.35 (d, J = 7.8 Hz, 1H), 7.30 – 7.25 (m, 1H), 5.01 (s, 2H), 1.10 (s, 9H). 13C NMR (150
MHz, CDCl3) δ 172.2, 156.8, 153.0, 149.2, 136.4, 136.3, 131.1, 129.3, 125.4, 122.0, 120.8, 83.3,
50.1, 27.4. HRMS (ESI): m/z [M+H]+ calcd for C18H20BrN2O3 391.0657 ; found 391.0659.
tert-butyl [1,1'-biphenyl]-4-carbonyl(quinolin-8-yl)carbamate (5a). White solid (petroleum ether /
acetone = 20:1, Rf = 0.15); 75.6 mg, yield 89 %; mp 155 ꢀ 156 °C. 1H NMR (600 MHz, DMSO) δ
8.93 (d, J = 4.2 Hz, 1H), 8.48 (d, J = 8.4 Hz, 1H), 8.06 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 7.2 Hz,
2H), 7.85 (d, J = 7.2 Hz, 2H), 7.82 (d, J = 7.2 Hz, 1H), 7.77 (d, J = 7.2 Hz, 2H), 7.69 (t, J = 7.8 Hz,
1H), 7.65 – 7.59 (m, 1H), 7.52 (t, J = 7.2 Hz, 2H), 7.44 (t, J = 7.2 Hz, 1H), 1.15 (s, 9H). 13C NMR
(150 MHz, DMSO) δ 172.3, 152.7, 150.7, 143.5, 143.1, 139.1, 136.8, 136.4, 135.8, 129.3, 129.1,
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128.8, 128.7, 128.4, 128.2, 126.9, 126.4, 122.0, 82.5, 27.0. HRMS (ESI): m/z [M+H]+ calcd for
C27H25N2O3 425.1865 ; found 425.1867.
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N-(quinolin-8-yl)-[1,1'-biphenyl]-4-carboxamide (5aa). White solid (petroleum ether / acetone =
20:1, Rf = 0.15); 61.0 mg, yield 94%; mp 153 ꢀ 154 °C.37 1H NMR (600 MHz, DMSO) δ 10.74 (s,
1H), 9.02 (s, 1H), 8.77 (d, J = 7.8 Hz, 1H), 8.49 (d, J = 8.4 Hz, 1H), 8.14 (d, J = 7.2 Hz, 2H), 7.94
(d, J = 7.2 Hz, 2H), 7.78 (m, 3H), 7.74 – 7.65 (m, 2H), 7.54 (t, J = 7.2 Hz, 2H), 7.46 (t, J = 7.2 Hz,
1H). 13C NMR (150 MHz, DMSO) δ 164.1, 149.2, 143.6, 138.9, 138.3, 136.8, 134.0, 133.1, 129.1,
128.3, 127.9, 127.7, 127.2, 127.1, 127.0, 122.4, 116.6. HRMS (ESI): m/z [M+H]+ calcd for
C22H17N2O 325.1341 ; found 325.1335.
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4'-methyl-1-(quinolin-8-yl)-[1,1'-biphenyl]-4-carboxamide (5ab). White solid (petroleum ether /
acetone = 20:1, Rf = 0.15); 63.6 mg, yield 94%; mp 154 ꢀ 155 °C. 1H NMR (600 MHz, CDCl3) (δ
ppm): 10.73 (s, 1H), 9.01 (s, 1H), 8.77 (d, J = 7.8 Hz, 1H), 8.49 (d, J = 8.4 Hz, 1H), 8.12 (d, J =
7.8 Hz, 2H), 7.91 (d, J = 7.8 Hz, 2H), 7.77 (d, J = 8.4 Hz, 1H), 7.68 (t, J = 8.4 Hz, 4H), 7.34 (d, J
= 7.8 Hz, 2H), 2.38 (s, 3H). 13C NMR (150 MHz, DMSO) δ 164.1, 149.2, 143.5, 138.2, 137.8,
136.8, 136.0, 134.0, 132.8, 129.7, 127.8, 127.7, 127.1, 126.9, 126.8, 122.4, 122.3, 116.5, 20.7.
HRMS (ESI): m/z [M+H]+ calcd for C23H19N2O 339.1497 ; found 339.1488.
4'-(tert-butyl)-1-(quinolin-8-yl)-[1,1'-biphenyl]-4-carboxamide (5ac). White solid (petroleum
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ether / acetone = 20:1, Rf = 0.15); 72.3 mg, yield 95%; mp 148 ꢀ 149 °C. H NMR (600 MHz,
DMSO) δ 10.73 (s, 1H), 9.01 (s, 1H), 8.77 (d, J = 7.2 Hz, 1H), 8.49 (d, J = 7.8 Hz, 1H), 8.12 (d, J
= 7.2 Hz, 2H), 7.91 (d, J = 7.2 Hz, 2H), 7.76 (d, J = 7.8 Hz, 1H), 7.70 (m, 4H), 7.54 (d, J = 7.2 Hz,
2H), 1.33 (s, 9H). 13C NMR (151 MHz, cdcl3) δ 165.12, 151.14, 148.19, 144.36, 138.68, 136.99,
136.34, 134.55, 133.41, 127.93, 127.74, 127.42, 127.15, 126.82, 125.87, 121.62, 121.58, 116.50,
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34.57, 31.28. HRMS (ESI): m/z [M+H]+ calcd for C26H25N2O 381.1967 ; found 381.1961.
4'-methoxy-1-(quinolin-8-yl)-[1,1'-biphenyl]-4-carboxamide (5ad). White solid (petroleum ether
/ acetone = 20:1, Rf = 0.15); 66.6 mg, yield 94%; mp 178 ꢀ 179 °C. 1H NMR (600 MHz, DMSO)
δ 10.72 (s, 1H), 9.01 (s, 1H), 8.77 (d, J = 7.2 Hz, 1H), 8.49 (d, J = 7.8 Hz, 1H), 8.10 (d, J = 7.8
Hz, 2H), 7.89 (d, J = 7.8 Hz, 2H), 7.75 (d, J = 7.8 Hz, 3H), 7.69 (d, J = 8.4 Hz, 2H), 7.09 (d, J =
7.8 Hz, 2H), 3.83 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 165.11, 159.69, 148.21, 144.11, 138.71,
136.31, 134.57, 133.02, 132.33, 128.22, 127.93, 127.75, 127.40, 126.78, 121.61, 121.56, 116.45,
114.33, 55.35. HRMS (ESI): m/z [M+H]+ calcd for C23H19N2O2 355.1447 ; found 355.1441.
4'-fluoro-1-(quinolin-8-yl)-[1,1'-biphenyl]-4-carboxamide (5ae). White solid (petroleum ether /
acetone = 20:1, Rf = 0.15); 65.1 mg, yield 95%; mp 152 ꢀ 153 °C. 1H NMR (600 MHz, DMSO)
δ 10.73 (s, 1H), 9.01 (s, 1H), 8.77 (d, J = 7.2 Hz, 1H), 8.48 (d, J = 8.4 Hz, 1H), 8.13 (d, J = 7.8
Hz, 2H), 7.92 (d, J = 7.8 Hz, 2H), 7.87 – 7.81 (m, 2H), 7.77 (d, J = 8.4 Hz, 1H), 7.74 – 7.65 (m,
2H), 7.37 (t, J = 8.4 Hz, 2H). 13C NMR (150 MHz, DMSO) δ 164.04, 162.33 (d, J = 244.2 Hz),
149.17, 142.52, 138.23, 136.77, 135.37, 134.00, 133.10, 129.02 (d, J = 8.4 Hz), 127.83, 127.71,
127.12, 127.04, 122.34, 122.31, 116.52, 115.91 (d, J = 21.2 Hz). HRMS (ESI): m/z [M+H]+
calcd for C22H16FN2O 343.1247 ; found 343.1261
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3'-fluoro-1-(quinolin-8-yl)-[1,1'-biphenyl]-4-carboxamide (5af). White solid (petroleum ether /
acetone = 20:1, Rf = 0.15); 63.0 mg, yield 92%; mp 93 ꢀ 94 °C. 1H NMR (600 MHz, DMSO) δ
10.74 (s, 1H), 9.02 (s, 1H), 8.76 (d, J = 7.2 Hz, 1H), 8.49 (d, J = 7.8 Hz, 1H), 8.14 (d, J = 7.8 Hz,
2H), 7.98 (d, J = 7.8 Hz, 2H), 7.77 (d, J = 7.8 Hz, 1H), 7.68 (m, 4H), 7.63 – 7.54 (m, 1H), 7.29 (t,
J = 7.8 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 164.84, 163.14 (d, J = 245.0 Hz), 148.21,
143.10, 142.15 (d, J = 7.7 Hz), 138.64, 136.38, 134.42, 134.26, 130.39 (d, J = 8.1 Hz), 127.93,
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127.86, 127.40, 127.33, 122.79, 121.71, 121.64, 116.58, 114.78 (d, J = 20.9 Hz), 114.05 (d, J =
22.2 Hz). HRMS (ESI): m/z [M+H]+ calcd for C22H16FN2O 343.1247 ; found 343.1257.
2'-fluoro-1-(quinolin-8-yl)-[1,1'-biphenyl]-4-carboxamide (5ag). White solid (petroleum ether /
acetone = 20:1, Rf = 0.15); 61.6 mg, yield 90%; mp 139 ꢀ 140 °C. 1H NMR (600 MHz, DMSO)
δ 10.75 (s, 1H), 9.01 (s, 1H), 8.77 (d, J = 7.2 Hz, 1H), 8.49 (d, J = 7.8 Hz, 1H), 8.16 (d, J = 7.8
Hz, 2H), 7.82 (d, J = 7.8 Hz, 2H), 7.78 (d, J = 8.4 Hz, 1H), 7.73 – 7.62 (m, 3H), 7.51 (d, J = 6.0
Hz, 1H), 7.44 – 7.34 (m, 2H). 13C NMR (150 MHz, CDCl3) δ 164.97, 159.72 (d, J = 247.5 Hz),
148.23, 139.26, 138.68, 136.34, 134.50, 134.13, 130.59, 129.67 (d, J = 8.1 Hz), 129.33 (d, J =
2.7 Hz), 127.94, 127.39, 124.50 (d, J = 3.5 Hz), 121.67, 121.64, 116.54, 116.22 (d, J = 22.7 Hz).
HRMS (ESI): m/z [M+H]+ calcd for C22H16FN2O 343.1247 ; found 343.1260.
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4'-chloro-1-(quinolin-8-yl)-[1,1'-biphenyl]-4-carboxamide (5ah). White solid (petroleum ether /
acetone = 20:1, Rf = 0.15); 66.7 mg, yield 93%; mp 153 ꢀ 154 °C. 1H NMR (600 MHz, DMSO)
δ 10.73 (s, 1H), 9.01 (s, 1H), 8.76 (d, J = 7.2 Hz, 1H), 8.49 (d, J = 8.4 Hz, 1H), 8.14 (d, J = 8.4
Hz, 2H), 7.95 (d, J = 8.4 Hz, 2H), 7.83 (d, J = 8.4 Hz, 2H), 7.77 (d, J = 7.8 Hz, 1H), 7.69 (d, J =
7.2 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H). 13C NMR (150 MHz, DMSO) δ 164.02, 149.20, 142.21,
138.26, 137.70, 136.78, 133.98, 133.44, 133.21, 129.04, 128.71, 127.84, 127.78, 127.17, 127.05,
122.37, 116.60. HRMS (ESI): m/z [M+H]+ calcd for C22H16ClN2O 359.0951 ; found 359.0945.
4'-hydroxy-1-(quinolin-8-yl)-[1,1'-biphenyl]-4-carboxamide (5ai). White solid (petroleum ether /
acetone = 20:1, Rf = 0.15); 59.2 mg, yield 87%; mp 218 ꢀ 219 °C. 1H NMR (600 MHz, DMSO)
δ 10.71 (s, 1H), 9.75 (s, 1H), 9.01 (s, 1H), 8.77 (d, J = 7.2 Hz, 1H), 8.48 (d, J = 8.4 Hz, 1H), 8.08
(d, J = 7.8 Hz, 2H), 7.85 (d, J = 7.8 Hz, 2H), 7.76 (d, J = 7.8 Hz, 1H), 7.70 (m, 2H), 7.64 (m,
2H), 6.91 (d, J = 7.8 Hz, 2H). 13C NMR (150 MHz, DMSO) δ 164.2, 158.0, 149.2, 143.7, 138.2,
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136.8, 134.1, 132.0, 129.6, 128.2, 127.9, 127.7, 127.1, 126.3, 122.4, 122.2, 116.5, 116.0. HRMS
(ESI): m/z [M+H]+ calcd for C22H17N2O2 341.1290 ; found 341.1281.
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N-(quinolin-8-yl)-4'-(trifluoromethoxy)-[1,1'-biphenyl]-4-carboxamide(5aj).
White
solid
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(petroleum ether / acetone = 20:1, Rf = 0.15); 74.3 mg, yield 91%; mp 150 ꢀ 151 °C. H NMR
(600 MHz, DMSO) δ 10.74 (s, 1H), 9.01 (s, 1H), 8.76 (d, J = 7.2 Hz, 1H), 8.49 (d, J = 7.8 Hz,
1H), 8.15 (d, J = 7.2 Hz, 2H), 7.96 (d, J = 7.2 Hz, 2H), 7.92 (d, J = 7.8 Hz, 2H), 7.77 (d, J = 7.8
Hz, 1H), 7.74 – 7.65 (m, 2H), 7.53 (d, J = 7.8 Hz, 2H). 13C NMR (150 MHz, CDCl3) δ 164.85,
149.12, 148.25, 143.04, 138.70, 138.65, 136.37, 134.46, 134.13, 128.55, 127.96, 127.89, 127.42,
127.34, 121.73, 121.66, 121.29, 119.61, 116.56 (OCF3 carbons are merging with other peaks).
HRMS (ESI): m/z [M+H]+ calcd for C23H16F3N2O2 409.1164 ; found 409.1173.
N-(quinolin-8-yl)-4'-(trifluoromethyl)-[1,1'-biphenyl]-4-carboxamide
(5ak). White
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(petroleum ether / acetone = 20:1, Rf = 0.15); 67.5 mg, yield 86%; mp 157 ꢀ 158 °C. H NMR
(600 MHz, DMSO) δ 10.74 (s, 1H), 9.01 (s, 1H), 8.76 (s, 1H), 8.48 (s, 1H), 8.17 (s, 2H), 8.01 (s,
4H), 7.88 (s, 2H), 7.77 (s, 1H), 7.70 (s, 2H). 13C NMR (150 MHz, CDCl3) δ 164.78, 148.26,
143.45, 142.94, 138.68, 136.44, 134.64, 134.42, 127.97, 127.58, 127.49, 127.44, 126.85, 125.82
(q, J = 3.0 Hz), 125.04, 124.14 (q, J = 270.8 Hz), 123.24, 121.80, 121.69, 116.63. HRMS (ESI):
m/z [M+H]+ calcd for C23H16F3N2O 393.1215 ; found 393.1221.
4'-acetyl-1-(quinolin-8-yl)-[1,1'-biphenyl]-4-carboxamide (5al). Yellow solid (petroleum ether /
acetone = 20:1, Rf = 0.15); 66.0 mg, yield 90%; mp 159 ꢀ 160 °C. 1H NMR (600 MHz, DMSO)
δ 10.75 (s, 1H), 9.02 (s, 1H), 8.77 (d, J = 7.2 Hz, 1H), 8.49 (d, J = 7.8 Hz, 1H), 8.17 (d, J = 7.8
Hz, 2H), 8.10 (d, J = 7.8 Hz, 2H), 8.02 (d, J = 7.8 Hz, 2H), 7.96 (d, J = 7.8 Hz, 2H), 7.78 (d, J =
8.4 Hz, 1H), 7.74 – 7.67 (m, 2H), 2.65 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 197.53, 164.75,
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148.26, 144.35, 143.05, 138.67, 136.36, 136.33, 134.57, 134.40, 128.94, 127.93, 127.89, 127.53,
127.39, 127.28, 121.75, 121.68, 116.52, 26.63. HRMS (ESI): m/z [M+H]+ calcd for C24H19N2O2
367.1447 ; found 367.1445.
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methyl 4'-(quinolin-8-ylcarbamoyl)-[1,1'-biphenyl]-4-carboxylate (5am). White solid (petroleum
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ether / acetone = 20:1, Rf = 0.15); 66.5 mg, yield 87%; mp 151 ꢀ 152 °C. H NMR (600 MHz,
DMSO) δ 10.74 (s, 1H), 9.01 (s, 1H), 8.76 (s, 1H), 8.48 (s, 1H), 8.16 (s, 2H), 8.09 (s, 2H), 8.00
(s, 2H), 7.95 (s, 2H), 7.77 (s, 1H), 7.70 (s, 2H), 3.89 (s, 3H). 13C NMR (150 MHz, CDCl3) δ
166.7, 164.7, 148.2, 144.2, 143.1, 138.6, 136.3, 134.5, 134.4, 130.1, 129.5, 127.9, 127.8, 127.5,
127.4, 127.1, 121.7, 121.6, 116.5, 52.1. HRMS (ESI): m/z [M+H]+ calcd for C24H19N2O3
383.1396 ; found 383.1389.
2',4'-dichloro-1-(quinolin-8-yl)-[1,1'-biphenyl]-4-carboxamide (5an). White solid (petroleum
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ether / acetone = 20:1, Rf = 0.15); 70.0 mg, yield 89%; mp 189 ꢀ 190 °C. H NMR (600 MHz,
DMSO) δ 10.74 (s, 1H), 9.00 (s, 1H), 8.76 (d, J = 7.8 Hz, 1H), 8.49 (d, J = 7.8 Hz, 1H), 8.14 (d,
J = 7.8 Hz, 2H), 7.82 (s, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.69 (m, 3H), 7.64 – 7.52 (m, 2H). 13C
NMR (150 MHz, CDCl3) δ 165.0, 148.3, 141.7, 138.8, 138.0, 136.4, 134.6, 134.5, 134.3, 133.2,
131.9, 129.9, 129.8, 128.0, 127.5, 127.3, 127.2, 121.8, 121.7 116.6. HRMS (ESI): m/z [M+H]+
calcd for C22H15Cl2N2O 393.0561 ; found 393.0555.
3',4'-dichloro-1-(quinolin-8-yl)-[1,1'-biphenyl]-4-carboxamide (5ao). White solid (petroleum
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ether / acetone = 20:1, Rf = 0.15); 70.8 mg, yield 90%; mp 158 ꢀ 159 °C. H NMR (600 MHz,
DMSO) δ 10.73 (s, 1H), 9.01 (s, 1H), 8.75 (d, J = 7.2 Hz, 1H), 8.49 (d, J = 7.8 Hz, 1H), 8.14 (d,
J = 7.8 Hz, 2H), 8.09 (s, 1H), 8.00 (d, J = 7.2 Hz, 2H), 7.85 – 7.75 (m, 3H), 7.69 (d, J = 7.8 Hz,
2H). 13C NMR (150 MHz, CDCl3) δ 164.7, 148.3, 141.9, 139.9, 138.7, 136.4, 134.5, 134.4,
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133.0, 132.2, 130.8, 128.9, 128.0, 127.4, 127.2, 126.3, 121.8, 121.7, 116.6. HRMS (ESI): m/z
[M+H]+ calcd for C22H15Cl2N2O 393.0561 ; found 393.0558.
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ether / acetone = 20:1, Rf = 0.15); 69.2 mg, yield 88%; mp 158 ꢀ 159 °C. H NMR (600 MHz,
CDCl3) (δ ppm): 10.73 (s, 1H), 9.01 (d, J = 3.6 Hz, 1H), 8.75 (d, J = 7.2 Hz, 1H), 8.49 (d, J = 7.2
Hz, 1H), 8.14 (m, 3H), 8.02 (d, J = 8.4 Hz, 2H), 7.87 (s, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.73 –
7.66 (m, 3H). 13C NMR (150 MHz, CDCl3) δ 164.68, 148.29, 142.93, 141.70, 138.69, 136.44,
135.47, 134.91, 134.38, 128.02, 127.85, 127.50, 127.46, 127.40, 125.70, 121.84, 121.71, 116.65.
HRMS (ESI): m/z [M+H]+ calcd for C22H15Cl2N2O 393.0561 ; found 393.0553.
4-(pyridin-4-yl)-1-(quinolin-8-yl)benzamide (5aq). White solid (petroleum ether / acetone = 20:1,
Rf = 0.15); 57.3 mg, yield 88%; mp 201 ꢀ 202 °C. 1H NMR (600 MHz, DMSO) δ 10.76 (s, 1H),
9.01 (s, 1H), 8.76 (d, J = 6.0 Hz, 1H), 8.72 (s, 2H), 8.49 (d, J = 6.6 Hz, 1H), 8.19 (d, J = 6.0 Hz,
2H), 8.08 (s, 2H), 7.83 (s, 2H), 7.78 (d, J = 6.6 Hz, 1H), 7.70 (s, 2H). 13C NMR (150 MHz,
CDCl3) δ 164.5, 150.3, 148.3, 147.1, 141.3, 138.6, 136.4, 135.4, 134.3, 128.0, 127.9, 127.4,
127.3, 121.8, 121.7, 121.6, 116.5. HRMS (ESI): m/z [M+H]+ calcd for C21H16N3O 326.1293 ;
found 326.1289.
4-(naphthalen-1-yl)-1-(quinolin-8-yl)benzamide(5ar). White solid (petroleum ether / acetone =
20:1, Rf = 0.15); 66.6 mg, yield 89%; mp 151 ꢀ 152 °C. 1H NMR (600 MHz, DMSO) δ 10.76 (s,
1H), 9.03 (s, 1H), 8.78 (d, J = 7.2 Hz, 1H), 8.49 (d, J = 7.8 Hz, 1H), 8.38 (s, 1H), 8.19 (d, J = 7.8
Hz, 2H), 8.08 (m, 4H), 7.98 (m, 2H), 7.78 (d, J = 7.8 Hz, 1H), 7.74 – 7.67 (m, 2H), 7.59 (d, J =
6.0 Hz, 2H). 13C NMR (150 MHz, CDCl3) δ 165.05, 148.20, 144.39, 138.66, 137.19, 136.38,
134.51, 133.71, 133.51, 132.86, 128.62, 128.28, 127.94, 127.84, 127.62, 127.58, 127.43, 126.45,
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126.31, 126.17, 125.16, 121.64, 116.55. HRMS (ESI): m/z [M+H]+ calcd for C26H19N2O
375.1497 ; found 375.1487.
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4-(dibenzo[b,d]furan-4-yl)-1-(quinolin-8-yl)benzamide (5as). White solid (petroleum ether /
acetone = 20:1, Rf = 0.15); 70.5 mg, yield 85%; mp 189 ꢀ 190 °C. 1H NMR (600 MHz, DMSO)
δ 10.80 (s, 1H), 9.03 (s, 1H), 8.80 (d, J = 6.6 Hz, 1H), 8.50 (d, J = 7.8 Hz, 1H), 8.25 (m, 4H),
8.20 (s, 2H), 7.84 (d, J = 6.6 Hz, 1H), 7.79 (t, J = 8.4 Hz, 2H), 7.72 (s, 2H), 7.60 (m, 3H), 7.47 (s,
1H). 13C NMR (150 MHz, CDCl3) δ 165.1, 156.2, 153.3, 148.3, 139.9, 138.8, 136.4, 134.6,
134.2, 129.1, 128.0, 127.7, 127.5, 127.4, 126.8, 125.1, 124.7, 124.0, 123.3, 122.9, 121.7, 120.7,
120.4, 116.7, 111.9. HRMS (ESI): m/z [M+H]+ calcd for C28H19N2O2 415.1447 ; found
415.1435.
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N-(quinolin-8-yl)-[1,1'-biphenyl]-3-carboxamide (5ba). White solid (petroleum ether / acetone =
20:1, Rf = 0.15); 61.6 mg, yield 95%; mp 82 ꢀ 83 °C.38 1H NMR (600 MHz, DMSO) δ 10.74 (s,
1H), 8.99 (d, J = 3.0 Hz, 1H), 8.74 (d, J = 7.8 Hz, 1H), 8.48 (d, J = 7.8 Hz, 1H), 8.29 (s, 1H),
8.03 (d, J = 7.2 Hz, 1H), 7.97 (d, J = 7.2 Hz, 1H), 7.79 (t, J = 8.4 Hz, 3H), 7.73 (t, J = 7.8 Hz,
1H), 7.71 – 7.67 (m, 2H), 7.54 (t, J = 7.8 Hz, 2H), 7.45 (t, J = 7.2 Hz, 1H). 13C NMR (150 MHz,
DMSO) δ 164.5, 149.2, 140.9, 139.3, 138.4, 136.7, 135.3, 134.0, 130.3, 129.6, 129.1, 128.0,
127.8, 127.0, 126.9, 125.9, 125.5, 122.5, 122.3, 117.0. HRMS (ESI): m/z [M+H]+ calcd for
C22H17N2O 325.1341 ; found 325.1336.
4'-(tert-butyl)-1-(quinolin-8-yl)-[1,1'-biphenyl]-3-carboxamide (5bb). White solid (petroleum
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ether / acetone = 20:1, Rf = 0.15); 72.3 mg, yield 95%; mp 116 ꢀ 117 °C. H NMR (600 MHz,
DMSO) δ 10.73 (s, 1H), 8.99 (d, J = 3.0 Hz, 1H), 8.75 (d, J = 7.8 Hz, 1H), 8.48 (d, J = 8.4 Hz,
1H), 8.27 (s, 1H), 8.01 (d, J = 7.8 Hz, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.78 (d, J = 8.4 Hz, 1H),
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7.70 (m, 5H), 7.55 (d, J = 7.8 Hz, 2H), 1.34 (s, 9H). 13C NMR (150 MHz, DMSO) δ 164.5, 150.4,
149.1, 140.8, 138.3, 136.7, 136.4, 135.2, 134.0, 130.1, 129.6, 127.8, 127.0, 126.5, 125.8, 125.6,
125.2, 122.4, 122.3, 116.8, 34.23, 31.02. HRMS (ESI): m/z [M+H]+ calcd for C26H25N2O
381.1967 ; found 381.1960.
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4'-methoxy-1-(quinolin-8-yl)-[1,1'-biphenyl]-3-carboxamide (5bc). White solid (petroleum ether
/ acetone = 20:1, Rf = 0.15); 66.6 mg, yield 94%; mp 74 ꢀ 75 °C. 1H NMR (600 MHz, DMSO) δ
10.72 (s, 1H), 8.99 (s, 1H), 8.74 (d, J = 7.2 Hz, 1H), 8.48 (d, J = 7.2 Hz, 1H), 8.24 (s, 1H), 7.97
(d, J = 6.0 Hz, 1H), 7.92 (d, J = 6.6 Hz, 1H), 7.82 – 7.64 (m, 6H), 7.10 (d, J = 7.2 Hz, 2H), 3.83
(s, 3H). 13C NMR (150 MHz, DMSO) δ 164.6, 159.3, 149.2, 140.6, 138.4, 136.7, 135.2, 134.1,
131.6, 129.8, 129.6, 128.1, 127.9, 127.0, 125.1, 124.9, 122.4, 122.3, 116.9, 114.5, 55.2. HRMS
(ESI): m/z [M+H]+ calcd for C23H19N2O2 355.1447 ; found 355.1440.
4'-fluoro-1-(quinolin-8-yl)-[1,1'-biphenyl]-3-carboxamide (5bd). White solid (petroleum ether /
acetone = 20:1, Rf = 0.15); 63.7 mg, yield 93%; mp 141 ꢀ 142 °C. 1H NMR (600 MHz, DMSO)
δ 10.73 (s, 1H), 8.99 (d, J = 4.2 Hz, 1H), 8.72 (d, J = 7.8 Hz, 1H), 8.48 (d, J = 8.4 Hz, 1H), 8.27
(s, 1H), 8.03 (d, J = 7.8 Hz, 1H), 7.95 (d, J = 7.8 Hz, 1H), 7.85 (dd, J = 8.4, 5.4 Hz, 2H), 7.78 (d,
J = 8.4 Hz, 1H), 7.74 – 7.67 (m, 3H), 7.37 (t, J = 9.0 Hz, 2H). 13C NMR (150 MHz, DMSO) δ
164.53, 162.17 (d, J = 243.5 Hz), 149.21, 139.85, 138.47, 136.73, 135.81, 135.32, 134.04,
130.27, 129.65, 129.01 (d, J = 8.0 Hz),, 127.86, 126.99, 125.87, 125.46, 122.53, 122.31, 117.08,
115.90 (d, J = 21.1 Hz),. HRMS (ESI): m/z [M+H]+ calcd for C22H16FN2O 343.1247 ; found
343.1251.
4'-chloro-1-(quinolin-8-yl)-[1,1'-biphenyl]-3-carboxamide (5be). White solid (petroleum ether /
acetone = 20:1, Rf = 0.15); 66.7 mg, yield 93%; mp 156 ꢀ 157 °C. 1H NMR (600 MHz, DMSO)
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δ 10.73 (s, 1H), 8.99 (d, J = 4.2 Hz, 1H), 8.72 (d, J = 7.8 Hz, 1H), 8.48 (d, J = 8.4 Hz, 1H), 8.30
(s, 1H), 8.05 (d, J = 7.8 Hz, 1H), 7.97 (d, J = 7.8 Hz, 1H), 7.84 (d, J = 8.4 Hz, 2H), 7.78 (d, J =
8.4 Hz, 1H), 7.73 (t, J = 7.8 Hz, 1H), 7.71 – 7.67 (m, 2H), 7.60 (d, J = 8.4 Hz, 2H). 13C NMR
(150 MHz, CDCl3) δ 165.16, 148.28, 140.57, 138.64, 138.56, 136.34, 135.77, 134.36, 133.87,
130.20, 129.25, 129.01, 128.40, 127.90, 127.36, 126.09, 125.92, 121.79, 121.66, 116.55. HRMS
(ESI): m/z [M+H]+ calcd for C22H16ClN2O 359.0951 ; found 359.0944.
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methyl 3'-(quinolin-8-ylcarbamoyl)-[1,1'-biphenyl]-4-carboxylate (5bf). White solid (petroleum
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ether / acetone = 20:1, Rf = 0.15); 65.0 mg, yield 85%; mp 166 ꢀ 167 °C. H NMR (600 MHz,
DMSO) δ 10.74 (s, 1H), 8.99 (d, J = 3.6 Hz, 1H), 8.72 (d, J = 7.8 Hz, 1H), 8.48 (d, J = 8.4 Hz,
1H), 8.36 (s, 1H), 8.10 (t, J = 9.0 Hz, 3H), 8.04 (d, J = 7.8 Hz, 1H), 7.97 (d, J = 7.8 Hz, 2H),
7.77 (dd, J = 15.6, 7.8 Hz, 2H), 7.69 (t, J = 6.6 Hz, 2H), 3.90 (s, 3H). 13C NMR (150 MHz,
CDCl3) δ 166.79, 165.08, 148.27, 144.49, 140.60, 138.60, 136.40, 135.81, 134.32, 130.49,
130.16, 129.31, 129.27, 127.91, 127.38, 127.11, 126.45, 126.42, 121.82, 121.67, 116.62,
52.15.HRMS (ESI): m/z [M+H]+ calcd for C24H19N2O3 383.1396 ; found 383.1395.
N-(quinolin-8-yl)-4'-(trifluoromethyl)-[1,1'-biphenyl]-3-carboxamide
(5bg). White
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(petroleum ether / acetone = 20:1, Rf = 0.15); 66.7 mg, yield 85%; mp 151 ꢀ 152 °C. H NMR
(600 MHz, DMSO) δ 10.74 (s, 1H), 8.98 (s, 1H), 8.72 (d, J = 7.5 Hz, 1H), 8.48 (d, J = 8.3 Hz,
1H), 8.36 (s, 1H), 8.10 (d, J = 7.4 Hz, 1H), 8.04 (d, J = 7.9 Hz, 3H), 7.89 (d, J = 7.8 Hz, 2H),
7.78 (t, J = 8.0 Hz, 2H), 7.69 (t, J = 7.0 Hz, 2H). 13C NMR (150 MHz, DMSO) δ 164.53, 162.98,
161.35, 149.21, 139.84, 138.46, 136.72, 135.79, 135.32, 134.03, 130.26, 129.64, 129.02, 128.97,
127.85, 126.98, 125.85, 125.44, 122.52, 122.29, 117.08, 115.96, 115.82 (CF3 carbons are
merging with other peaks). HRMS (ESI): m/z [M+H]+ calcd for C23H16F3N2O 393.1215 ; found
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2',4'-dichloro-1-(quinolin-8-yl)-[1,1'-biphenyl]-3-carboxamide (5bh). White solid (petroleum
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ether / acetone = 20:1, Rf = 0.15); 69.2 mg, yield 88%; mp 139 ꢀ 140 °C. H NMR (600 MHz,
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DMSO) δ 10.72 (s, 1H), 8.98 (d, J = 3.6 Hz, 1H), 8.72 (d, J = 7.8 Hz, 1H), 8.48 (d, J = 8.4 Hz,
1H), 8.17 (s, 1H), 8.08 (d, J = 7.8 Hz, 1H), 7.83 (d, J = 7.8 Hz, 1H), 7.75 (m, 3H), 7.68 (t, J = 7.8
Hz, 2H), 7.46 (t, J = 9.6 Hz, 1H), 7.28 (t, J = 8.4 Hz, 1H). 13C NMR (150 MHz, DMSO) δ
164.27, 149.19, 138.40, 136.73, 134.99, 134.91, 133.98, 132.34, 132.11, 132.08, 132.05, 132.02,
129.39, 127.84, 127.56, 126.99, 126.36, 123.97, 122.52, 122.32, 116.97, 112.33, 112.19, 104.82,
104.65, 104.48. HRMS (ESI): m/z [M+H]+ calcd for C22H15Cl2N2O 393.0561 ; found 393.0553.
3-(pyridin-4-yl)-1-(quinolin-8-yl)benzamide (5bi). White solid (petroleum ether / acetone = 20:1,
Rf = 0.15); 56.6 mg, yield 87%; mp 151 ꢀ 152 °C. 1H NMR (600 MHz, DMSO) δ 10.74 (s, 1H),
8.99 (d, J = 3.0 Hz, 1H), 8.72 (d, J = 6.0 Hz, 2H), 8.48 (d, J = 7.2 Hz, 1H), 8.42 (s, 1H), 8.13 (d,
J = 7.8 Hz, 1H), 8.10 (d, J = 7.8 Hz, 1H), 7.85 (d, J = 6.0 Hz, 2H), 7.81 – 7.77 (m, 2H), 7.72 –
7.66 (m, 2H), 7.66 – 7.60 (m, 1H). 13C NMR (150 MHz, CDCl3) δ 164.7, 150.2, 148.3, 147.3,
138.7, 138.6, 136.3, 136.0, 134.2, 132.0, 130.1, 129.5, 127.8, 127.3, 127.2, 126.2, 121.9, 121.6,
116.5. HRMS (ESI): m/z [M+H]+ calcd for C21H16N3O 326.1293 ; found 326.1295.
4-phenyl-1-(quinolin-8-yl)-1-naphthamide (5ca). White solid (petroleum ether / acetone = 20:1,
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Rf = 0.15); 70.4 mg, yield 94%; mp 72 ꢀ 73 °C. H NMR (600 MHz, CDCl3) δ 10.48 (s, 1H),
9.08 (d, J = 7.2 Hz, 1H), 8.77 (s, 1H), 8.59 (d, J = 8.4 Hz, 1H), 8.21 (d, J = 7.8 Hz, 1H), 7.96 (d,
J = 7.8 Hz, 2H), 7.67 (t, J = 7.8 Hz, 1H), 7.62 – 7.56 (m, 2H), 7.54 – 7.44 (m, 8H). 13C NMR
(150 MHz, CDCl3) δ 167.8, 148.3, 143.3, 140.2, 138.5, 136.4, 134.8, 134.1, 132.1, 130.7, 129.9,
128.3, 128.0, 127.6, 127.4, 127.1, 126.5, 125.9, 125.8, 124.9, 121.9, 121.7, 116.7. HRMS (ESI):
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