An efficient one-pot synthesis of 1,4-disubstituted 3-amino-2-pyridone derivatives via three-component reactions of alkynyl aldehydes and amines with ethyl 2-((diphenylmethylene)amino)acetate

Article abstract of DOI:10.1016/j.tet.2012.03.106

A facile and efficient one-pot synthesis of 1,4-disubstituted 3-amino-2-pyridone derivatives via three-component reactions of readily available alkynyl aldehydes, amines, and ethyl 2-((diphenylmethylene)amino) acetate has been developed. The alkynyl aldeh

Full text of DOI:10.1016/j.tet.2012.03.106

Tetrahedron 68 (2012) 4152e4158
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Tetrahedron
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An efficient one-pot synthesis of 1,4-disubstituted 3-amino-2-pyridone
derivatives via three-component reactions of alkynyl aldehydes and amines with
ethyl 2-((diphenylmethylene)amino)acetate
,
a
a
a,b,
Qingfa Zhou a , Xueping Chu , Weifang Tang , Tao Lu
*
*
a School of Basic Sciences, China Pharmaceutical University, Nanjing 210009, PR China
b State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A facile and efficient one-pot synthesis of 1,4-disubstituted 3-amino-2-pyridone derivatives via three-
component reactions of readily available alkynyl aldehydes, amines, and ethyl 2-((diphenylmethylene)
amino)acetate has been developed. The alkynyl aldehyde substrates and the amine partners can be
flexibly varied to achieve a range of 3-amino-2-pyridone derivatives, which could exert interesting
chemical and biological properties. The reaction mechanism for the formation of 3-amino-2-pyridone
derivatives is briefly explained.
Received 7 February 2012
Received in revised form 19 March 2012
Accepted 27 March 2012
Available online 30 March 2012
Keywords:
Alkynyl aldehyde
Ó 2012 Elsevier Ltd. All rights reserved.
3-Amino-2-pyridone
Amine
Synthesis
Ethyl 2-((diphenylmethylene)amino)acetate
1. Introduction
added diene;6 and they have been applied as a key synthetic in-
termediate to synthesize some complex natural products.7 Conse-
2-Pyridone ring represents an important structural motif oc-
curring in many natural products and related congeners because
many of the molecules containing this structural motif exhibit
a wide range of biological activities.1 For example, cytisine (1),
which was extracted from the seeds of Laburnum anagyroides has
been recognized as a partial agonist of nicotinic cholinergic re-
ceptors (nAChRs) with a nanomolar affinity and a high selectivity
for the a4b2 subtype;2 farinosone (2), which was isolated from the
entomopathogenic fungi Paecilomyces farinosus and Paecilomyces
militaris induces and enhances neurite outgrowth in the PC-12 cell
line;3 apiosporamide (3), which was isolated from the fungus
Apiospora montagnei Saccardo exhibits potent antifungal activity
against the coprophilous fungus Ascobolus furfuraceus and shows
antibacterial activity against Bacillus subtilis and Staphylococcus
aureus (Fig. 1).4 2-Pyridone derivatives are also a versatile synthon
for the preparation of a variety of other nitrogen-containing het-
quently, a large number of methods have been developed for the
synthesis of 2-pyridones and their derivatives.8 The most common
strategies involve the modification of the preconstructed hetero-
cyclic ring and the construction of the heterocyclic skeleton from
acyclic compounds. Due to the importance of 2-pyridone skeleton,
to develop new and efficient methodologies for diversely func-
tionalized construction of 2-pyridone is still highly desired.
Amino-2-pyridones are an important subset of 2-pyridones;
they exhibit a wide range of interesting biological activities,9 which
includes as interleukin-2 inducible T-cell (Itk) inhibitor,9a glycogen
synthase-3b
inhibitor,9b insulin-like growth factor-1 receptor (IGF-
1R) inhibitor,9c EP3 receptor antagonist,9d selective tissue Factor
VIIa inhibitor,9e and other medicinal properties.9f,g Among the
syntheses of amino-2-pyridone derivatives, the most general ap-
proaches for accessing amino substituent on the 2-pyridones are
reduction of the nitro group on the 2-pyridones9f,10 or amination of
halopyridines,11 but each of them often suffers from significant
limitations, such as multistep procedures, harsh conditions, low
yields, or poor chemo- and regioselectivity. Recently, Rigo and co-
workers reported the synthesis of 4-amino-2-pyridones by the
reaction of amines with a dicarbonylallene;12a Schirok and co-
workers developed the synthesis of 6-amino-2-pyridones by the
reaction of acyclic ketene aminals with propiolic acid ester;12b Nan
erocycles, such as b-lactam, quinolizidine, pyridine, piperidine, and
indolizidine alkaloids;5 the diene portion of the molecule can un-
dergo DielseAlder cycloaddition reactions with a dienophile, or
one double bond of the molecule may act as a dienophile to an
* Corresponding authors. Tel.: þ86 025 86185160; fax: þ86 025 86285179; e-mail
addresses: zhouqingfa@cpu.edu.cn (Q. Zhou), lut163@163.com (T. Lu).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.03.106

Q. Zhou et al. / Tetrahedron 68 (2012) 4152e4158
4153
Fig. 1. Representative natural product containing 2-pyridone moiety.
and co-workers described the synthesis of 3-amino-2-pyridone by
the ring-closing metathesis reaction of
-amino acrylamide.12c
amount of desired products (Table 1, entries 4 and 5). Fortunately,
the reaction performed in the presence of sodium hydroxide
(NaOH) at room temperature and afforded a yellow solid in 17%
isolated yield in 24 h, and the product was characterized as 4a by
NMR and MS analysis (Table 1, entry 6). More gratifyingly, rapid
reaction was observed to provide desired product 4a in 84% isolated
yield by using sodium hydride (NaH) at room temperature for 3 h
(Table 1, entry 7). Other strong bases were also tested as the pro-
moter in the reaction, such as sodium methanolate (MeONa), po-
tassium 2-methylpropan-2-olate (tBuOK), and they provided less
satisfactory results (Table 1, entries 8 and 9). The amount of NaH
employed had a significance effect on the reaction rate and the
yield (Table 1, entries 7, 10e12). As shown in Table 1, the temper-
ature had an effect on this reaction. When the reaction temperature
decreased from room temperature to 0 ꢀC, no desired product was
found (Table 1, entry 13). Among the solvents we examined,
dichloromethane, THF, and toluene were proved to be usable sol-
vents for the reaction (Table 1, entries 10, 14, and 16). The choice of
Et2O as the solvent gave the desired product 4a in 71% isolated yield
(Table 1, entry 15). Thus, the optimal reaction conditions for this
one-pot reaction were determined to be 120 mol % sodium hydride
as the promoter in dichloromethane at room temperature.
a
Despite the plethora of these synthetic processes, there is a gen-
eral lack of simple and effective procedures with which to syn-
thesize 1,4-disubstituted 3-amino-2-pyridone derivatives from
simple and readily available starting materials. Therefore, the
search for an operational convenient, modular, and broadly appli-
cable 1,4-disubstituted 3-amino-2-pyridone derivatives synthesis
still represents a challenging research task. We have previously
reported the synthesis of a,b-dehydroamino acid derivatives and 3-
amino-2-pyrone derivatives from the reaction of alkynyl ketones
with N-(diphenylmethylene)glycinates.13 As continuation of these
efforts in our laboratory, we wish to report herein an efficient and
convenient one-pot synthesis of a variety of biologically interesting
3-amino-2-pyridone derivatives via three-component reactions of
amines, alkynyl aldehydes and N-(diphenylmethylene)glycinates.
2. Results and discussion
At the outset of our study, we first chose aniline (1a), 3-
phenylpropiolaldehyde (2a), and ethyl 2-((diphenylmethylene)
amino)acetate (3) as the standard substrates to search for suitable
reaction conditions for the synthesis 3-amino-2-pyridone de-
rivatives, and the results are shown in Table 1. It was disappointing
that no desired product was found by TLC when organic bases were
used, such as triphenylphosphine (Ph3P), triethylamine (Et3N)
(Table 1, entries 2 and 3). Both sodium carbonate (Na2CO3) and
potassium carbonate (K2CO3) as Lewis bases afforded only trace
With these results in hand, we first screened several amines to
explore the scope of the reaction, and the results are shown in
Table 2. The electronic nature of the substituent on the phenyl
moiety has an obvious influence on the activity of the reaction.
Anilines with an electron-donating substituent afforded better
yields than aniline (Table 2, entries 1, 6, and 7). Anilines with an
Table 1
Optimization of the reaction conditions of the three-component reactions of aniline (1a), 3-phenylpropiolaldehyde (2a), and ethyl 2-((diphenylmethylene) amin)acetate (3)a
Entry
Base (mol %)
Solvent
Temp (ꢀC)
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
None
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
0
24
24
24
24
24
24
3
3
3
5
5
0
0
0
Et3N (200)
Ph3P (200)
Na2CO3 (200)
K2CO3 (200)
NaOH (200)
NaH (200)
NaOMe (200)
tBuOK (200)
NaH (120)
NaH (100)
NaH (50)
Trace
Trace
17
84
52
44
92
86
52
0
9
10
11
12
13
14
15
16
5
5
5
5
NaH (120)
NaH (120)
NaH (120)
NaH (120)
rt
rt
rt
91
71
88
Et2O
Toluene
5
a
All reactions were first carried out with 1a (0.6 mmol) and 2a (0.6 mmol) in the absence of solvent at rt for 30 min, then 3 (0.5 mmol), solvent (2.0 mL), and base were
successively added and the resulting mixture was carried out at rt under nitrogen atmosphere.
b
Isolated yield based on 3.

4154
Q. Zhou et al. / Tetrahedron 68 (2012) 4152e4158
Table 2
Reaction of amines, alkynyl aldehydes, and ethyl 2-((diphenylmethylene)amino)acetatea
Entry
R1
R2
Product
Yieldb (%)
1
2
3
4
5
6
7
8
Ph, 1a
Ph, 2a
Ph, 2a
Ph, 2a
Ph, 2a
Ph, 2a
Ph, 2a
Ph, 2a
Ph, 2a
Ph, 2a
Ph, 2a
Ph, 2a
Ph, 2a
4a
4b
4c
4d
4e
4f
4g
dc
4h
4i
92
81
86
92
96
97
95
d
3-FePh, 1b
3-ClePh, 1c
3-BrePh, 1d
3-MeOePh, 1e
4-ClePh, 1f
4-MeOePh, 1g
4-NO2ePh, 1h
2,4-Cl2ePh, 1i
3,4-Cl2ePh, 1j
3-F-4-ClePh, 1k
tBu, 1l
PhCH2, 1m
Ph, 1a
Ph, 1a
Ph, 1a
Ph, 1a
9
95
94
82
d
10
11
12
13
14
15
16
17
18
19
20
4j
dc
dc
4k
4l
Ph, 2a
d
4-F-Ph, 2b
4-Cl-Ph, 2c
4-Me-Ph, 2d
4-MeO-Ph, 2e
3-Cl-Ph, 2f
3-Me-Ph, 2g
nPr, 2i
97
94
98
98
95
97
d
4m
4n
4o
4p
dc
Ph, 1a
Ph, 1a
Ph, 1a
a
All reactions were first carried out with 1 (0.6 mmol) and 2 (0.6 mmol) in the absence of solvent at rt for 30 min, then 3 (0.5 mmol), dichloromethane (2.0 mL), and sodium
hydride (0.6 mmol) were successively added and the resulting mixture was carried out at rt for 5 h under nitrogen atmosphere.
b
Isolated yield based on 3.
No desired product was found.
c
electron-withdrawing substituent such as 4-F aniline afforded
a lower yield than aniline (Table 2, entries 1 and 2). Even aniline
with a strong electron-withdrawing substituent such as 4-nitro
aniline did not yield any desired product (Table 2, entry 8). The
feasibility of employing aliphatic amines instead of aryl amines
in the reaction was also investigated. Unfortunately, when 2-
methylpropan-2-amine was used, no desired product was
obtained (Table 2, entry 12). And the use of phenylmethanamine
could not afford the expected product (Table 2, entry 13). It was
noteworthy that when benzene-1,4-diamine and benzene-1,3-
diamine were submitted to the reaction conditions, bis-3-amino-
2-pyridone derivatives were formed besides the mono-3-amino-2-
pyridone derivatives (Scheme 1). The reaction of benzene-1,4-
diamine (0.6 mmol) and 3-phenylpropiolaldehyde (0.6 mmol)
with ethyl 2-((diphenylmethylene)amino)acetate (0.5 mmol) per-
formed at room temperature for 5 h under the optimal reaction
conditions gave products 6a (5%) and 7a (79%). Alternately, treat-
ment of benzene-1,3-diamine in the reaction provided products 6b
(7%) and 7b (67%).
conditions to afford the corresponding products in good to excel-
lent yields, when aromatic alkynyl aldehydes were examined under
the reaction conditions; while no desired product was obtained,
when aliphatic alkynyl aldehyde was tested under the reaction
conditions. The substituents on the phenyl ring of the aromatic
alkynyl aldehydes have no obvious effect on the yields of the re-
actions. For example, the reaction of 3-(4-fluorophenyl)propio-
laldehyde or 3-(4-methoxyphenyl)propiolaldehyde, under the
conditions described, gave the corresponding products 4k and 4n
in 97% and 98% yields, respectively.
On the base of our results and previous works,13,14 a plausible
mechanism to account for the formation of the 3-amino-2-
pyridone derivatives 4 is presented in Scheme 2 as follows: So-
dium hydride deprotonates the active methylene proton of the
ethyl 2-((diphenylmethylene)amino)acetate
3 to generate in-
termediate 9. The intermediate 9 then undergoes conjugate addi-
tion to the alkynyl imine 8,15 which is formed by condensation of
alkynyl aldehyde and amine to give 10, followed by proton transfer
to give compound 11. The intermediate 11 would undergo double
Scheme 1.
A variety of alkynyl aldehydes were then submitted to the re-
action; these results are summarized in Table 2. It was observed
that the reactions proceeded smoothly under the optimized
bond migration and the subsequent intramolecular aza-cyclization
reaction of 13 would give the product 3-amino-2-pyridone de-
rivatives 4.

Q. Zhou et al. / Tetrahedron 68 (2012) 4152e4158
4155
Scheme 2. Proposed mechanism for the formation of 3-amino-2-pyridone derivatives.
3. Conclusions
dried with sodium sulfate. The solvents were evaporated in vacuo
and then the residue was purified by silica gel chromatography
(SiO2; ethylacetate/PE, 1:10e1:5) to afford 3-amino-2-pyridone
derivatives 4aep, 6, and 7.
In summary, we have developed an efficient route to di-
verse 1,4-disubstituted 3-amino-2-pyridone derivatives 4 through
a mild, room temperature, one-pot procedure by combining
alkynyl aldehydes, amines, and ethyl 2-((diphenylmethylene)
amino)acetate. A range of 3-amino-2-pyridone derivatives would
be achieved because the alkynyl substrates and the amine partners
can be flexibly varied. Owing to the interest of the amino-2-
pyridone derivatives for the design of biologically relevant com-
pounds, this methodology offers a route for the synthesis of di-
verse 1,4-disubstituted 3-amino-2-pyridone derivatives. The
potential utilization and extension of the scope of the methodol-
ogy and the examination of biological activity of the 3-amino-2-
pyridone derivatives are currently under investigation in our
laboratory.
4.2.1. 3-(Diphenylmethyleneamino)-1,4-diphenylpyridin-2(1H)-one
(4a). Yield 92%; yellow solid; mp 57e58 ꢀC. IR (KBr):
n
¼3059, 1724,
1647, 1612, 1591, 1491, 1444, 1398, 754, 694 cmꢂ1 1H NMR
.
(300 MHz, DMSO-d6):
d
¼7.56e7.42 (m, 9H), 7.38e7.29 (m, 10H),
6.74 (d, J¼6.6 Hz, 2H), 6.25 (d, J¼7.2, 1H) ppm. 13C NMR (75 MHz,
DMSO-d6):
d¼169.3, 156.0, 140.7, 139.1, 136.9, 133.6, 132.1, 130.9,
128.9, 128.89, 128.8, 128.7, 128.6, 128.4, 128.1, 128.0, 127.9, 127.7,
127.6, 126.7, 126.4, 106.6 ppm. HRMS (ESI): calcd for C30H23N2O
[MþH]þ 427.1805; found 427.1811.
4.2.2. 3-(Diphenylmethyleneamino)-1-(3-fluorophenyl)-4-phenylpy-
ridin-2(1H)-one (4b). Yield 81%; yellow solid; mp 64e65 ꢀC. IR
4. Experimental section
4.1. General
(KBr):
n
¼3032, 1747, 1645, 1618, 1599, 1487, 1398, 756, 694 cmꢂ1
.
1H NMR (300 MHz, DMSO-d6):
d
¼7.59e7.43 (m, 5H), 7.37e7.16
(m, 13H), 6.73 (d, J¼6.0 Hz, 2H), 6.27 (d, J¼7.2 Hz, 1H) ppm. 13C
NMR (75 MHz, DMSO-d6):
d
¼169.5, 163.3, 155.8, 142.0, 139.0,
All reactions were performed in anhydrous solvents under an N2
atmosphere. THF, Et2O, and toluene were distilled from K and Na
metal, respectively. CH2Cl2 and acetone were distilled from CaH2.
PE refers to petroleum ether (boiling range 60e90 ꢀC). Alkynyl al-
dehyde16 and ethyl 2-((diphenylmethylene)amino)acetate13a were
prepared following known procedures. Amines are commercially
available without further purification. Reaction progress was
monitored using thin layer chromatography (TLC), which was vi-
sualized by ultraviolet light (254 nm). Flash chromatography was
conducted with silica gel 200e300 mesh. IR spectra were recorded
on an FTIR-8400s spectrometer. Melting points were obtained on
a Yanaco-241 apparatus and are uncorrected. 1H and 13C NMR
spectra were recorded in DMSO-d6 using a Bruker Avance 300
spectrometer or a Bruker Avance 500 spectrometer: chemical shifts
137.7, 136.5, 133.8, 131.9, 130.9, 130.6, 130.5, 128.7, 128.3, 128.2,
128.0, 127.8, 127.6, 126.7, 122.6, 122.5, 115.0, 114.2, 106.8 ppm.
HRMS (ESI): calcd for C30H22FN2O [MþH]þ 445.1711; found
445.1710.
4.2.3. 1-(3-Chlorophenyl)-3-(diphenylmethyleneamino)-4-phenylpy-
ridin-2(1H)-one (4c). Yield 86%; yellow solid; mp 65e66 ꢀC. IR
(DMSO):
n
¼3080, 1649, 1610, 1587, 1489, 1475, 1446, 1292, 785, 758,
694 cmꢂ1
.
1H NMR (300 MHz, DMSO-d6):
d
¼7.58e7.42 (m, 7H),
7.40e7.36 (m, 7H), 7.33e7.28 (m, 4H), 6.74 (d, J¼6.3 Hz, 2H), 6.27 (d,
J¼7.2 Hz, 1H) ppm. 13C NMR (75 MHz, DMSO-d6):
¼169.5, 155.8,
d
141.7, 138.9, 137.7, 136.7, 133.9, 132.9, 131.8, 131.0, 130.9, 130.5, 128.8,
128.7, 128.4, 128.2, 128.1, 128.0, 127.8, 127.6, 126.8, 126.5, 125.2,
106.8 ppm. HRMS (ESI): calcd for C30H22ClN2O [MþH]þ 461.1415;
found 461.1420.
(d) are given in parts per million, coupling constants (J) in hertz.
High-resolution mass spectra were recorded on a Waters/Micro-
mass QTOF MS spectrometer.
4.2.4. 1-(3-Bromophenyl)-3-(diphenylmethyleneamino)-4-phenylpy-
ridin-2(1H)-one (4d). Yield 92%; yellow solid; mp 62e63 ꢀC. IR
4.2. General procedure for the synthesis of 3-amino-2-
pyridone derivatives
(KBr):
(500 MHz, DMSO-d6):
n
¼3016, 1656, 1639, 1627, 1398, 823, 761, 624 cmꢂ1. 1H NMR
d
¼7.65e7.64 (m, 1H), 7.57e7.56 (m, 2H),
7.52e7.43 (m, 5H), 7.42e7.37 (m, 5H), 7.35e7.28 (m, 5H), 6.74 (d,
A mixture of alkynyl aldehyde (0.6 mmol) and amine (0.6 mmol)
was stirred at room temperature for 30 min, and then ethyl 2-
((diphenylmethylene)amino)acetate (0.5 mmol), dichloromethane
(2 mL), and sodium hydride (0.6 mmol) were successively added.
The resulting mixture was stirred at room temperature for 5 h
under nitrogen atmosphere. Saturated aqueous NaHCO3 (10 mL)
was added to quench the reaction. The mixture was extracted with
dichloromethane (3ꢁ10 mL). The combined organic layers were
J¼7.0 Hz, 2H), 6.27 (d, J¼7.0 Hz, 1H) ppm. 13C NMR (125 MHz,
DMSO-d6):
d
¼171.1, 157.2, 142.2, 140.6, 138.4, 137.4, 137.3, 134.5,
131.4,131.0,130.8,130.5,130.1,129.9,129.7,128.9,128.8,128.3,128.1,
128.0, 127.6, 125.3, 122.5, 108.1 ppm. HRMS (ESI): calcd for
C30H22BrN2O [MþH]þ 505.0910; found 505.0917.
4.2.5. 3-(Diphenylmethyleneamino)-1-(3-methoxyphenyl)-4-phenyl-
pyridin-2(1H)-one (4e). Yield 96%; yellow solid; mp 66e67 ꢀC. IR

4156
Q. Zhou et al. / Tetrahedron 68 (2012) 4152e4158
(KBr):
n
¼3055, 1647, 1608, 1489, 1292, 783, 756, 694 cmꢂ1
.
1H
107.0 ppm. HRMS (ESI): calcd for C30H21ClFN2O [MþH]þ 479.1321;
NMR (300 MHz, DMSO-d6):
d
¼7.58e7.21 (m, 15H), 7.02 (dd,
found 479.1325.
J1¼8.4 Hz, J2¼2.1 Hz, 1H), 6.87 (d, J¼8.4 Hz, 1H), 6.82 (d, J¼2.1 Hz,
1H), 6.75 (d, J¼6.6 Hz, 2H), 6.24 (d, J¼7.2 Hz, 1H), 3.78 (s, 3H)
4.2.11. 3-(Diphenylmethyleneamino)-4-(4-fluorophenyl)-1-
phenylpyridin-2(1H)-one (4k). Yield 97%; yellow solid; mp
ppm. 13C NMR (75 MHz, DMSO-d6):
d
¼169.3, 159.4, 155.8, 141.8,
139.0, 136.9, 133.7, 132.1, 130.9, 129.7, 128.7, 128.6, 128.3, 128.1,
128.0, 127.7, 127.6, 127.5, 126.7, 118.4, 113.7, 112.2, 112.1, 106.5,
55.2 ppm. HRMS (ESI): calcd for C31H25N2O2 [MþH]þ 457.1911;
found 457.1916.
54e55 ꢀC. IR (KBr):
n
¼3014, 1703, 1647, 1543, 1508, 1398, 823, 759,
624 cmꢂ1. 1H NMR (500 MHz, DMSO-d6):
d
¼7.59 (d, J¼7.0 Hz, 2H),
7.52e7.49 (m, 3H), 7.44e7.41 (m, 5H), 7.35e7.28 (m, 6H), 7.22e7.18
(m, 2H), 6.77 (d, J¼6.5 Hz, 2H), 6.23 (d, J¼7.0 Hz, 1H) ppm. 13C NMR
(125 MHz, DMSO-d6):
d¼169.6, 162.3, 155.9, 140.7, 139.0, 137.7,
4.2.6. 1-(4-Chlorophenyl)-3-(diphenylmethyleneamino)-4-phenylpy-
ridin-2(1H)-one (4f). Yield 97%; yellow solid; mp 149e150 ꢀC. IR
136.5, 133.2, 133.1, 132.7, 131.0, 130.5, 128.9, 128.8, 128.7, 128.2,
127.9, 127.6, 126.7, 126.3, 115.0, 106.4 ppm. HRMS (ESI): calcd for
C30H22FN2O [MþH]þ 445.1711; found 445.1716.
(KBr):
n
¼3051, 1643, 1606, 1589, 1579, 1491, 1317, 1286, 1082, 754,
694 cmꢂ1
.
1H NMR (500 MHz, DMSO-d6):
d¼7.58e7.49 (m, 5H),
7.44e7.40 (m, 2H), 7.36e7.25 (m, 11H), 6.71 (d, J¼7.2 Hz, 2H), 6.26
4.2.12. 4-(4-Chlorophenyl)-3-(diphenylmethyleneamino)-1-
phenylpyridin-2(1H)-one (4l). Yield 94%; brown oil; IR (DMSO):
(d, J¼7.5 Hz, 1H) ppm. 13C NMR (125 MHz, DMSO-d6):
d¼169.5,
156.0, 139.4, 139.0, 137.7, 136.8, 133.8, 132.5, 132.0, 131.0, 129.0,
128.9, 128.8, 128.7, 128.4, 128.3, 128.2, 128.1, 127.9, 127.6, 126.7,
106.9 ppm. HRMS (ESI): calcd for C30H22ClN2O [MþH]þ 461.1415;
found 461.1413.
n
¼3032, 1655, 1637, 1610, 1508, 1398, 823, 759 cmꢂ1
.
1H NMR
¼7.58 (d, J¼7.5 Hz, 2H), 7.52 (m, 3H),
(500 MHz, DMSO-d6):
d
7.45e7.39 (m, 7H), 7.35e7.28 (m, 6H), 6.76 (d, J¼7.5 Hz, 2H), 6.24 (d,
J¼7.2 Hz, 1H) ppm. 13C NMR (125 MHz, DMSO-d6):
¼169.6, 155.8,
d
140.6, 139.1, 136.8, 135.6, 132.5, 132.4, 132.3, 130.2, 129.3, 128.9,
128.7,128.5,128.3,128.2,128.0,127.9,127.6,126.6, 126.3, 106.2 ppm.
HRMS (ESI): calcd for C30H22ClN2O [MþH]þ 461.1415; found
461.1421.
4.2.7. 3-(Diphenylmethyleneamino)-1-(4-methoxyphenyl)-4-phenyl-
pyridin-2(1H)-one (4g). Yield 95%; yellow solid; mp 178e179 ꢀC. IR
(KBr):
n
¼3057, 1647, 1622, 1602, 1599, 1545, 1487, 1400, 756,
694 cmꢂ1. 1H NMR (500 MHz, DMSO-d6):
d
¼7.56 (d, J¼7.0 Hz, 2H),
7.51 (d, J¼7.5 Hz, 1H), 7.44 (d, J¼7.0 Hz, 2H), 7.36e7.25 (m, 9H), 7.22
(d, J¼9.0 Hz, 2H), 7.04 (d, J¼9.0 Hz, 2H), 6.72 (d, J¼7.0 Hz, 2H), 6.21
(d, J¼7.5 Hz, 1H), 3.80 (s, 3H) ppm. 13C NMR (125 MHz, DMSO-d6)
4.2.13. 3-(Diphenylmethyleneamino)-1-phenyl-4-p-tolylpyridin-
2(1H)-one (4m). Yield 98%; yellow solid; mp 76e77 ꢀC. IR (KBr):
n
¼3032, 1657, 1639, 1608, 1510, 1398, 821, 759, 623 cmꢂ1. 1H NMR
d
¼169.3, 158.5, 156.2, 139.0, 137.8, 136.9, 136.5, 133.6, 132.5, 130.9,
(500 MHz, DMSO-d6):
d
¼7.59 (d, J¼7.0 Hz, 2H), 7.51e7.40 (m, 6H),
128.8, 128.7, 128.4, 128.2, 128.0, 127.7, 127.6,127.4, 126.7,126.4, 114.1,
106.4, 55.3 ppm. HRMS (ESI): calcd for C31H25N2O2 [MþH]þ
457.1911; found 457.1916.
7.32e7.26 (m, 8H), 7.18 (d, J¼7.0 Hz, 2H), 6.76 (d, J¼6.5 Hz, 2H), 6.23
(d, J¼7.5 Hz, 1H), 2.28 (s, 3H) ppm. 13C NMR (125 MHz, DMSO-d6):
d
¼169.2, 155.8, 140.7, 138.7, 137.8, 137.2, 136.5, 133.9, 133.8, 132.0,
131.4, 130.9, 129.1, 128.7, 128.6, 128.3, 128.2, 127.8, 127.5, 126.6,
126.3, 106.5, 20.6 ppm. HRMS (ESI): calcd for C31H25N2O [MþH]þ
441.1961; found 441.1967.
4.2.8. 1-(2,4-Dichlorophenyl)-3-(diphenylmethyleneamino)-4-phen-
ylpyridin-2(1H)-one (4h). Yield 95%; yellow solid; mp
213e214 ꢀC. IR (KBr):
n
¼3076, 1647, 1622, 1606, 1581, 1479,
1442, 1400, 758, 698 cmꢂ1 1H NMR (500 MHz, DMSO-d6):
¼7.85 (s, 1H), 7.61e7.49 (m, 4H), 7.44 (t, J¼7.4 Hz, 2H),
7.37e7.23 (m, 10H), 6.71 (d, J¼6.0 Hz, 2H), 6.27 (d, J¼7.0 Hz, 1H)
ppm. 13C NMR (125 MHz, DMSO-d6):
.
4.2.14. 3-(Diphenylmethyleneamino)-4-(4-methoxyphenyl)-1-
phenylpyridin-2(1H)-one (4n). Yield 98%; yellow solid; mp
d
66e67 ꢀC. IR (KBr):
n
¼3012, 1659, 1647, 1543, 1508, 1398, 1055, 823,
d
¼169.6, 155.7, 139.2, 137.7,
759, 624 cmꢂ1. 1H NMR (500 MHz, DMSO-d6):
d
¼7.60 (d, J¼7.5 Hz,
137.5, 137.2, 136.7, 136.3, 134.2, 134.1, 131.9, 131.0, 130.8, 129.4,
128.9, 128.8, 128.5, 128.4, 128.2, 128.0, 127.9, 127.6, 126.9,
107.0 ppm. HRMS (ESI): calcd for C30H21Cl2N2O [MþH]þ
495.1025; found 495.1031.
2H), 7.53e7.47 (m, 3H), 7.45e7.41 (m, 3H), 7.40e7.38 (m, 2H), 7.35
(d, J¼7.5 Hz, 1H), 7.30e7.24 (m, 5H), 6.95e6.92 (m, 2H), 6.79 (d,
J¼7.0 Hz, 2H), 6.25 (d, J¼7.0H, 1H), 3.74 (s, 3H) ppm. 13C NMR
(125 MHz, DMSO-d6):
d
¼169.3, 158.8, 155.7, 140.8, 138.4, 137.9,
136.6, 133.7, 131.9, 130.9, 129.8, 129.1, 129.0, 128.9, 128.7, 128.6,
128.2, 127.8, 127.5, 126.7, 126.3, 113.5, 106.5, 55.0 ppm. HRMS (ESI):
calcd for C31H25N2O2 [MþH]þ 457.1911; found 457.1916.
4.2.9. 1-(3,4-Dichlorophenyl)-3-(diphenylmethyleneamino)-4-
phenylpyridin-2(1H)-one (4i). Yield 94%; yellow solid; mp
123e124 ꢀC. IR (KBr):
n
¼3078, 1651, 1614, 1587, 1471, 1444, 1290,
1130, 756, 696 cmꢂ1
.
1H NMR (500 MHz, DMSO-d6):
d
¼7.78 (d,
4.2.15. 4-(3-Chlorophenyl)-3-(diphenylmethyleneamino)-1-
phenylpyridin-2(1H)-one (4o). Yield 95%; yellow solid; mp
J¼9.0 Hz,1H), 7.65 (d, J¼2.5 Hz,1H), 7.57 (d, J¼7.0 Hz, 2H), 7.51e7.34
(m, 10H), 7.31e7.26 (m, 3H), 6.72 (d, J¼7.0 Hz, 2H), 6.28 (d, J¼7.5 Hz,
56e57 ꢀC. IR (KBr):
n
¼3030, 1646, 1608, 1589, 1564, 1491, 1444, 756,
1H) ppm. 13C NMR (125 MHz, DMSO-d6):
d¼169.6, 155.8, 140.1,
692 cmꢂ1. 1H NMR (500 MHz, DMSO-d6):
d
¼7.57 (d, J¼5.0 Hz, 2H),
138.9, 137.7, 136.7, 136.4, 134.0, 131.7, 131.1, 131.0, 130.8, 130.7, 128.9,
128.8, 128.7, 128.4, 128.2, 128.1, 127.9, 127.7, 126.9, 126.8, 107.0 ppm.
HRMS (ESI): calcd for C30H21Cl2N2O [MþH]þ 495.1025; found
495.1023.
7.53e7.50 (m, 3H), 7.45e7.43 (m, 3H), 7.40e7.29 (m, 10H), 6.73 (d,
J¼5.0 Hz, 2H), 6.25 (d, J¼7.0 Hz, 1H) ppm. 13C NMR (125 MHz,
DMSO-d6):
d
¼169.6, 156.1, 140.6, 139.4, 138.8, 137.6, 136.3, 132.7,
132.4, 131.9,131.1, 129.8, 128.9, 128.7, 128.6, 128.4, 128.2, 127.9, 127.7,
127.6, 126.9, 126.7, 126.3, 106.1 ppm. HRMS (ESI): calcd for
C30H22ClN2O [MþH]þ 461.1415; found 461.1421.
4.2.10. 1-(4-Chloro-3-fluorophenyl)-3-(diphenylmethyleneamino)-4-
phenylpyridin-2(1H)-one (4j). Yield 82%; yellow solid; mp
147e148 ꢀC. IR (KBr):
n
¼3070, 1651, 1616, 1597, 1572, 1487, 1440,
4.2.16. 3-(Diphenylmethyleneamino)-1-phenyl-4-m-tolylpyridin-
2(1H)-one (4p). Yield 97%; yellow solid; mp 45e46 ꢀC. IR (KBr):
1311, 759, 694 cmꢂ1
.
1H NMR (500 MHz, DMSO-d6):
d
¼7.73 (t,
J¼8.5, 1H), 7.58 (d, J¼6.0, 2H), 7.51 (dd, J1¼10.0 Hz, J2¼2.0 Hz, 2H),
n
¼3032, 1655, 1647, 1610, 1508, 1400, 823, 759, 624 cmꢂ1. 1H NMR
7.49e7.22 (m, 12H), 6.72 (d, J¼6.0 Hz, 2H), 6.27 (d, J¼7.0 Hz, 1H)
(500 MHz, DMSO-d6):
d
¼7.56 (d, J¼6.5 Hz, 2H), 7.53e7.50 (m, 3H),
ppm. 13C NMR (125 MHz, DMSO-d6):
d
¼169.6, 157.7, 155.7, 140.5,
7.45e7.42 (m, 3H), 7.35e7.21 (m, 7H), 7.14e7.09 (m, 3H), 6.70 (d,
140.4, 139.0, 137.7, 136.4, 133.9, 131.7, 131.0, 130.6, 128.8, 128.7,
128.4, 128.2, 128.0, 127.9, 127.6, 126.7, 123.9, 119.2, 115.8,
J¼6.5 Hz, 2H), 6.22 (d, J¼7.0 Hz, 1H), 2.25 (s, 3H) ppm. 13C NMR
(125 MHz, DMSO-d6):
d¼169.2, 156.1, 140.7, 139.1, 137.8, 137.0, 136.7,

Q. Zhou et al. / Tetrahedron 68 (2012) 4152e4158
4157
136.4, 133.6, 132.0, 130.8, 129.1, 128.9, 128.7, 128.6, 128.2, 128.1,
References and notes
127.9, 127.8, 127.5, 126.7, 126.3, 125.4, 106.6, 20.8 ppm. HRMS (ESI):
calcd for C31H25N2O [MþH]þ 441.1961; found 441.1966.
1. (a) Grontas, W. C.; Stanga, M. A.; Brobaker, M. J.; Huang, T. L.; Moi, M. L.; Carroll,
R. T. J. Med. Chem. 1985, 28, 1106e1109; (b) Nagarajan, M.; Xiao, X. S.; Antony, S.;
Kohlhagen, G.; Pommier, Y.; Cushman, M. J. Med. Chem. 2003, 46, 5712e5724;
(c) Cox, R. J.; O’Hagan, D. J. Chem. Soc., Perkin Trans. 1 1991, 2537e2540; (d)
Kozikowski, A. P.; Campiani, G.; Sun, L.-Q.; Wang, S.; Saxena, A.; Doctor, B. P. J.
Am. Chem. Soc. 1996, 118, 11357e11362; (e) Misra, R.; Pandey, R. C.; Silverton, J.
V. J. Am. Chem. Soc. 1982, 104, 4478e4479; (f) Hsiang, Y. H.; Hertzberg, R.; Hecht,
S.; Liu, L. F. J. Biol. Chem. 1985, 260, 14873e14878; (g) Liu, J. S.; Zhu, Y. L.; Yu, C.
M.; Zhou, Y. Z.; Han, Y. Y.; Wu, F. W.; Qi, B. F. Can. J. Chem. 1986, 64, 837e839; (h)
Jayasinghe, L.; Abbas, H. K.; Jacob, M. R.; Herath, W. H. M. W.; Nanayakkara, N.
P. D. J. Nat. Prod. 2006, 69, 439e442.
2. (a) Houllier, N.; Gopisetti, J.; Lestage, P.; Lasne, M.-C.; Rouden, J. Bioorg. Med.
Chem. Lett. 2010, 20, 6667e6670; (b) Dale, H. H.; Laidlaw, P. P. J. Pharmacol. Exp.
Ther. 1912, 3, 205e221; (c) Ing, H. R. J. Chem. Soc. 1931, 2195e2203; (d) Ing, H. R.
J. Chem. Soc. 1932, 2778e2780.
3. (a) Cheng, Y.; Schneider, B.; Riese, U.; Schubert, B.; Li, Z.; Hamburger, M. J. Nat.
Prod. 2004, 67, 1854e1858; (b) Cheng, Y.; Schneider, B.; Riese, U.; Schubert, B.;
Li, Z.; Hamburger, M. J. Nat. Prod. 2006, 69, 436e438; (c) Jessen, H. J.; Schu-
macher, A.; Shaw, T.; Pfaltz, A.; Gademann, K. Angew. Chem., Int. Ed. 2011, 50,
4222e4226.
4.2.17. 1,10-(1,4-Phenylene)bis(3-((diphenylmethylene)amino)-4-
phenylpyridin-2(1H)-one) (6a). Yield 5%; yellow solid; mp
304e305 ꢀC. IR (DMSO):
n
¼3018, 1657, 1639, 1562, 1510, 823, 761,
624 cmꢂ1. 1H NMR (500 MHz, DMSO-d6):
d
¼7.58 (d, J¼7.0 Hz, 4H),
7.53 (m, 2H), 7.46e7.41 (m, 10H), 7.39e7.35 (m, 10H), 7.32e7.28 (m,
6H), 6.73 (d, J¼7.0 Hz, 4H), 6.2 9 (d, J¼7.0 Hz, 2H) ppm. 13C NMR
(125 MHz, DMSO-d6):
d
¼169.5, 156.0, 140.0, 139.1, 136.8, 133.8,
131.9, 128.8, 128.7, 128.4, 128.3, 128.26, 128.21, 128.0, 127.8, 127.7,
127.6, 127.1, 126.7, 106.9 ppm. HRMS (ESI): calcd for C54H39N4O2
[MþH]þ 775.3068; found 775.3053.
4.2.18. 1-(4-Aminophenyl)-3-(diphenylmethyleneamino)-4-
phenylpyridin-2(1H)-one (7a). Yield 79%; yellow solid; mp
176e177 ꢀC. IR (DMSO):
n
¼3018, 1656, 1639, 1398, 823, 761,
4. (a) Alfatafta, A. A.; Gloer, J. B.; Scott, J. A.; Malloch, D. J. Nat. Prod. 1994, 57,
1696e1702; (b) Williams, D. R.; Kammler, D. C.; Donnell, A. F.; Goundry, W. R. F.
Angew. Chem. 2005, 117, 6873e6876.
624 cmꢂ1
.
1H NMR (500 MHz, DMSO-d6):
d
¼7.56 (d, J¼7.5 Hz,
2H), 7.50 (t, J¼7.0 Hz, 1H), 7.43 (t, J¼8.0 Hz, 2H), 7.36e7.23 (m,
8H), 7.22 (d, J¼7.0 Hz, 1H), 6.91 (d, J¼8.5 Hz, 2H), 6.70 (d,
J¼7.0 Hz, 2H), 6.62 (d, J¼8.5 Hz, 2H), 6.15 (d, J¼7.0 Hz, 1H), 5.32
5. (a) Elbein, A. D.; Molyneux, R. J. In Alkaloids: Chemical and Biological Perspec-
tives; Pelletier, S. W., Ed.; Wiley: New York, NY, 1981; Vol. 5, pp 1e54; (b) Jones,
G.; Stanforth, S. P. In Organic Reactions; Paquette, L. A., Ed.; Wiley: New York,
NY, 1997; Vol. 49, pp 1e330; (c) Tanaka, K.; Fujiwara, T.; Urbanczyk-Lipkowska,
Z. Org. Lett. 2002, 4, 3255e3257; (d) Angibaud, P. R.; Venet, M. G.; Filliers, W.;
Broeckx, R.; Ligny, Y. A.; Muller, P.; Poncelet, V. S.; End, D. W. Eur. J. Org. Chem.
(br s, 2H) ppm. 13C NMR (125 MHz, DMSO-d6):
d
¼169.0, 156.3,
148.3, 138.9, 137.9, 137.0, 136.5, 133.2, 132.8, 130.8, 129.3, 128.7,
128.6, 128.3, 128.1, 127.9, 127.6, 127.5, 126.7, 126.6, 113.3,
106.0 ppm. HRMS (ESI): calcd for C30H24N3O [MþH]þ 442.1914;
found 442.1913.
ꢀ
2004, 479e486; (e) Casamitjana, N.; Lopez, V.; Jorge, A.; Bosch, J.; Molins, E.;
Roig, A. Tetrahedron 2000, 56, 4027e4042; (f) Fujita, R.; Watanabe, K.; Ikeura,
W.; Ohtake, Y.; Hongo, H. Heterocycles 2000, 53, 2607e2610; (g) Fujita, R.;
Watanabe, K.; Ikeura, W.; Ohtake, Y.; Hongo, H.; Harigaya, Y.; Matsuzaki, H.
Tetrahedron 2001, 57, 8841e8850; (h) Aubert, C.; Betschmann, P.; Eichberg, M.
J.; Gandon, V.; Heckrodt, T. J.; Lehmann, J.; Malacria, M.; Masjost, B.; Paredes, E.;
Vollhardt, KP. C.; Whitener, G. D. Chem.dEur. J. 2007, 13, 7443e7465.
6. (a) Dilling, W. L.; Tefertiller, N. B.; Mitchell, A. B. Mol. Photochem. 1973, 5,
371e409; (b) Afarinkia, K.; Vinader, V.; Nelson, T. D.; Posner, G. H. Tetrahedron
1992, 48, 9111e9171; (c) Okamura, H.; Nagaike, H.; Iwagawa, T.; Nakatani, M.
Tetrahedron Lett. 2000, 41, 8317e8321; (d) Soh, JY.-T.; Tan, C.-H. J. Am. Chem. Soc.
2009, 131, 6904e6905; (e) Fujita, R.; Watanabe, K.; Nishiuchi, Y.; Honda, R.;
Matsuzaki, H.; Hongo, H. Chem. Pharm. Bull. 2001, 49, 601e605; (f) Chou, S. S. P.;
Chen, P. W. Tetrahedron 2008, 64, 1879e1887.
4.2.19. 1,10-(1,3-Phenylene)bis(3-((diphenylmethylene)amino)-4-
phenylpyridin-2(1H)-one) (6b). Yield 7%; yellow solid
216e217 ꢀC. IR (KBr):
¼3026, 1647, 1612, 1591, 1489, 1315, 1290,
754, 694 cmꢂ1 1H NMR (500 MHz, DMSO-d6):
¼7.64e7.50 (m,
7H), 7.42e7.27 (m, 25H), 6.74 (d, J¼6.0 Hz, 4H), 6.31 (d, J¼7.0 Hz,
2H) ppm. 13C NMR (125 MHz, DMSO-d6):
; mp
n
.
d
d
¼169.5, 155.9, 140.9,
139.1, 137.8, 136.8, 136.5, 133.8, 132.0, 131.0, 129.3, 128.8, 128.7,
128.4, 128.2, 128.1, 127.9, 127.6, 126.8, 126.0, 124.3, 106.9 ppm.
HRMS (ESI): calcd for C54H39N4O2 [MþH]þ 775.3068; found
775.3070.
7. (a) Snider, B. B.; Che, Q. Org. Lett. 2004, 6, 2877e2880; (b) Chen, P.; Carroll, P. J.;
Sieburth, S. M. Org. Lett. 2010, 12, 4510e4512.
8. (a) Torres, M.; Gil, S.; Parra, M. Curr. Org. Chem. 2005, 9, 1757e1779; (b) Hop-
kins, G. C.; Jonak, J. P.; Minnemeyer, H. J.; Tieckelmann, H. J. Org. Chem. 1967, 32,
4040e4044; (c) Comins, D. L.; Saha, J. K. J. Org. Chem. 1996, 61, 9623e9624; (d)
Williams, D.; Lowder, P.; Gu, Y.-G.; Brooks, D. A. Tetrahedron Lett. 1997, 38,
331e334; (e) Du, W. Tetrahedron 2003, 59, 8649e8687; (f) Cristau, H.-J.; Cellier,
P. P.; Spindler, J.-F.; Taillefer, M. Chem.dEur. J. 2004, 10, 5607e5622; (g) Pan, W.;
Dong, D.; Wang, K.; Zhang, J.; Wu, R.; Xiang, D.; Liu, Q. Org. Lett. 2007, 9,
2421e2423; (h) Xiang, D.; Yang, Y.; Zhang, R.; Liang, Y.; Pan, W.; Huang, J.;
Dong, D. J. Org. Chem. 2007, 72, 8593e8596; (i) Chen, L.; Zhao, Y.-L.; Liu, Q.;
Cheng, C.; Piao, C.-R. J. Org. Chem. 2007, 72, 9259e9263; (j) Gorobets, N. Y.;
Yousefi, B. H.; Belaj, F.; Kappe, C. O. Tetrahedron 2004, 60, 8633e8644; (k)
Gibson, K. R.; Hitzel, L.; Mortishire-Smith, R. J.; Gerhard, U.; Jelley, R. A.; Reeve,
A. J.; Rowley, M.; Nadin, A.; Owens, A. P. J. Org. Chem. 2002, 67, 9354e9360; (l)
Robin, A.; Julienne, K.; Meslin, J. C.; Deniaud, D. Tetrahedron Lett. 2004, 45,
9557e9559; (m) Yamamoto, Y.; Takagishi, H.; Itoh, K. Org. Lett. 2001, 3,
2117e2119; (n) Padwa, A.; Sheehan, S. M.; Straub, C. S. J. Org. Chem. 1999, 64,
8648e8659; (o) Padwa, A.; Heidelbaugh, T. M.; Kuethe, J. T. J. Org. Chem. 2000,
65, 2368e2378; (p) Chikhalikar, S.; Bhawe, V.; Ghotekar, B.; Jachak, M.; Gha-
gare, M. J. Org. Chem. 2011, 76, 3829e3836; (q) Chun, Y. S.; Ryu, K. Y.; Ko, Y. O.;
Hong, J. Y.; Hong, J.; Shin, H.; Lee, S. J. Org. Chem. 2009, 74, 7556e7558; (r)
Ravinder, M.; Sadhu, P. S.; Rao, V. J. Tetrahedron Lett. 2009, 50, 4229e4232; (s)
Zhang, R.; Zhang, D.; Guo, Y.; Zhou, G.; Jiang, Z.; Dong, D. J. Org. Chem. 2008, 73,
9504e9507; (t) Xiang, D.; Kewei Wang, K.; Liang, Y.; Zhou, G.; Dong, D. Org. Lett.
2008, 10, 345e348; (u) Imase, H.; Noguchi, K.; Hirano, M.; Tanaka, K. Org. Lett.
2008, 10, 3563e3566; (v) Su, Y.; Miao Zhao, M.; Han, K.; Song, G.; Li, X. Org. Lett.
2010, 12, 5462e5465; (w) Pemberton, N.; Jakobsson, L.; Almqvist, F. Org. Lett.
2006, 8, 935e938; (x) Mathews, A.; Anabha, E. R.; Sasikala, K. A.; Lathesh, K. C.;
Krishnaraj, K. U.; Sreedevi, K. N.; Prasanth, M.; Devaky, K. S.; Asokan, C. V.
Tetrahedron 2008, 64, 1671e1675.
4.2.20. 1-(3-Aminophenyl)-3-(diphenylmethyleneamino)-4-
phenylpyridin-2(1H)-one (7b). Yield 67%; yellow solid; mp
165e166 ꢀC. IR (KBr):
n
¼3012, 1658, 1643, 1626, 1545, 1512, 1400,
823, 759, 624 cmꢂ1
.
1H NMR (500 MHz, DMSO-d6):
d
¼7.56 (d,
J¼7.5 Hz, 2H), 7.52 (t, J¼6.9 Hz, 1H), 7.44 (t, J¼7.3 Hz, 2H), 7.41e7.33
(m, 5H), 7.30e7.25 (m, 2H), 7.24 (d, J¼7.0 Hz, 1H), 7.12 (t, J¼8.0 Hz,
1H ), 6.70 (d, J¼7.5 Hz, 2H), 6.61 (dd, J1¼8.0 Hz, J2¼1.5 Hz, 1H), 6.46
(m, 1H), 6.37 (dd, J1¼8.0 Hz, J2¼1.5 Hz, 1H), 6.17 (d, J¼7.5 Hz, 1H),
5.35 (br s, 2H) ppm. 13C NMR (125 MHz, DMSO-d6):
d
¼169.2, 156.0,
149.3, 141.6, 139.1, 137.8, 136.9, 133.3, 132.2, 130.9, 129.2, 128.8,
128.7, 128.6, 128.4, 128.2, 127.9, 127.6, 127.5, 126.6, 113.3, 113.2, 111.6,
106.1 ppm. HRMS (ESI): calcd for C30H24N3O [MþH]þ 442.1914;
found 442.1913.
Acknowledgements
This work was financially supported by the National Natural
Science Foundation of China (Grant No. 21102179) and Funda-
mental Research Funds for the Central Universities (No.
JKZ2011011).
9. (a) Charrier, J.-D.; Miller, A.; Kay, D. P.; Brenchley, G.; Twin, H. C.; Collier, P. N.;
Ramaya, S.; Keily, S. B.; Durrant, S. J.; Knegtel, R. M. A.; Tanner, A. J.; Brown, K.;
Curnock, A. P.; Jimenez, J.-M. J. Med. Chem. 2011, 54, 2341e2350; (b) Coffman,
K.; Brodney, M.; Cook, J.; Lanyon, L.; Pandit, J.; Sakya, S.; Schachter, J.; Tseng-
Lovering, E.; Wessel, M. Bioorg. Med. Chem. Lett. 2011, 21, 1429e1433; (c) Ve-
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Copies of NMR spectra for all products related to this article can
be found online at doi:10.1016/j.tet.2012.03.106.

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