Molecular iodine promoted synthesis of new pyrido[2,3-d]pyrimidin-4-ols

Article abstract of DOI:10.1002/cjoc.201180294

A highly efficient synthesis of novel pyrido[2,3-d]pyrimidin-4-ols was developed via an iodine-catalyzed tandem oxidative cyclization under focused microwave irradiation. Pyrido[2,3-d]pyrimidin-4-ols were obtained from easily available 2-amino-4-aryl-6-ar

Full text of DOI:10.1002/cjoc.201180294

FULL PAPER
Molecular Iodine Promoted Synthesis of New
Pyrido[2,3-d]pyrimidin-4-ols
Wang, Xicun*,a(王喜存)
Liang, Junlinga(梁军灵)
Bai, Linb(白林)
Quan, Zhengjuna(权正军)
a Key Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education, Gansu Key
Laboratory of Polymer Materials, College of Chemistry and Chemical Engineering,
Northwest Normal University, Lanzhou, Gansu 730070, China
b Institute of Green Chemistry Experiment and Teaching, Lanzhou City University, Lanzhou, Gansu 730070, China
A highly efficient synthesis of novel pyrido[2,3-d]pyrimidin-4-ols was developed via an iodine-catalyzed tan-
dem oxidative cyclization under focused microwave irradiation. Pyrido[2,3-d]pyrimidin-4-ols were obtained from
easily available 2-amino-4-aryl-6-arylnicotinamides and benzylic amines with good to excellent yields.
Keywords iodine catalysis, oxidative cyclization, microwave irradiation, pyrido[2,3-d]pyrimidin-4-ol
Introduction
Microwave irradiation have been utilized extensively
as a clean source of energy for the synthesis of organic
compounds.20,21 Some important reviews have been
published in recent years, covering a large number of
microwave induced reactions.22,23 Herein, we developed
a simple and efficient approach to the synthesis of novel
2-phenylpyrido[2,3-d]pyrimidin-4-ols with I2 and TBHP
as the catalytic oxidation system. Various 2-phenylpyrido-
[2,3-d]pyrimidin-4-ols were prepared from 2-amino-4-
aryl-6-arylnicotinamides and benzylic amines via a tan-
dem reaction following sp3 C— H functionalization un-
der metal-free conditions. The reaction was performed
in a focused microwave synthesis system so that it was
possible to control the temperature, pressure, microwave
power and reaction times easily and with high degree of
reproducibility.
Pyrido[2,3-d]pyrimidine ring system is present in a
number of biologically active compounds which includes
antitumor,1 antipyretic,2 analgesic,3 antihistaminic,4
PDE4 inhibitor,5 adenosine kinase inhibitor,6 tyrosine
kinase inhibitor7 and diuretic8,9 activities. Although
there are a number of well-established methods to prepare
pyrido[2,3-d]pyrimidine ring system, they mainly depend
on the availability of the indispensable metal-catalyzed
C— H functionalization and subsequent formation of
C— N bonds.10-12 And toxic or expensive metal catalysts,
hazardous oxidants and organic solvents are still in-
volved in most of these systems. The metal residue and
environmental pollution are always the main problem
with metal-mediated or metal-catalyzed systems.
There are only a few examples on C— H function-
alization under transition-metal-free conditions. Re-
cently, Wang et al.13,27 reported an efficient nonmetal
catalytic oxidation system by using molecular iodine.
Zeng et al.14 reported iodine catalyzed one-pot synthesis
of tetrazolo[1,5-a]pyrimidine core. He et al.15 described
iodine-mediated synthesis of 3H-indoles. Mehta et al.16
reported iodine/palladium approaches to the synthesis of
polyheterocyclic compounds. Carmen et al.17 reported
that pyrido[2,3-d]pyrimidin-4-ols show a significant in
vitro cytotoxicity. Hannah et al.18 found that β-keto es-
ters could condens with amidines to give 2,6-substituted
pyrimidin-4-ols. Xiao et al.19 reported the HATU-
mediated coupling of 4-hydroxyquinazolines with
amines. Therefore there is a definite need for catalytic
systems that can use green oxidants without metals af-
fording pyrido[2,3-d]pyrimidin-4-ol derivatives.
Results and discussion
In order to synthesize 5-aryl-2-phenyl-7-arylpyrido-
[2,3-d]pyrimidin-4-ols, various 2-amino-4-aryl-6-aryl-
nicotinamides were employed as starting material to
develop a cluster of new compounds and the key inter-
mediate according to a known procedure.24,25 Initially,
when 2-amino-4,6-diphenylnicotinamide (1a, 1 mmol)
was treated with benzylic amine (2 mmol), iodine (0.05
mmol) and pyridine, and aqueous tert-butyl hydroper-
oxide (TBHP) (2 mmol) under focused microwave irra-
diation at 90 ℃, 10 W for 8 min, 55% of 2a was ob-
tained (Table 1, Entry 1). In the absence of pyridine, the
reaction can give a higher yield (Table 1, Entry 2).
Without iodine, no product was observed (Table 1, En-
try 3). Then other environmental benign oxidants, such
*
E-mail: wangxicun@nwnu.edu.cn; Tel.: 0086-0931-7971971
Received November 25, 2010; revised March 20, 2011; accepted April 13, 2011.
Project supported by the National Natural Science Foundation of China (No. 20902073), the Natural Science Foundation of Gansu Province (No.
096RJZA116) and Scientific and Technological Innovation Engineering Program of Northwest Normal University (No. nwnu-kjcxgc-03-64).
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Chin. J. Chem. 2011, 29, 1646— 1650

Molecular Iodine Promoted Synthesis of New Pyrido[2,3-d]pyrimidin-4-ols
as t-BuOOBu-t, aqueous H2O2, and oxygen, were also
examined, but only aqueous H2O2 can generate a trace
amount of the product (Table 1, Entry 4). No better re-
sult was observed when various solvents were intro-
duced to the reaction (Table 1, Entries 5— 8). Raising
the reaction temperature to 100 ℃ can increase the reac-
tion yield to 78%. Further raising the reaction tempera-
ture cannot enhance the reaction yield obviously (Table
1, Entry 10). After the ratios of iodine, benzylic amine,
and TBHP were optimized, the reaction yield was im-
proved to 90% (Table 1, Entries 11— 17). Therefore, the
optimal reaction conditions is, the mixture of 2-amino-
4,6-diphenylnicotinamide (1a, 1 mmol) and benzylic
amine (2.5 mmol) was heated at 100 ℃ for 8 min with
iodine (0.10 mmol) as catalyst and TBHP (2 mmol) as
oxidant (Table 1, Entry 16).
Subsequently, we investigated the scope of the reac-
tion substrates under the optimized conditions, as shown
in Table 2. The introduction of electron-withdrawing
group (such as Br, Cl, F) and electron-donating group
(such as CH3, CH3O) to the phenyl ring of 2-amino-
4-aryl-6-arylnicotinamides affected the reaction slightly.
However, when the phenyl ring of benzylic amine was
replaced with aliphatic amine such as ethylamine, the
desired product was not obtained and we isolated the
starting material.
The analysis of the structure of the product 2a after
D2O exchange experiment by 1H NMR revealed that the
peak at δ 12.54 disappeared, which could be attributed
to the replacement of hydrogen atom of hydroxyl group
of the product 2a by deuterium atom of D2O. Besides,
the IR spectrum of the product 2a showed a peak at
－
1
3444 cm , which further confirmed the presence of the
OH in the product 2a.
A tentative mechanism was proposed in Scheme 1.
First, intermediate I can be generated from 2-amino-4,6-
diphenylnicotinamide (1a) and benzylic amine. Subse-
quently, I is oxidized to intermediate III via sp3 C— H
functionalization under the reaction conditions.26 Then
intermediate III is converted to the pyrido[2,3-d]-
pyrimidin-4-ol (2) product after intramolecular cycliza-
tion and further oxidization in tandem process.13,27
Conclusion
In summary, a practical and efficient synthesis of
novel pyrido[2,3-d]pyrimidin-4-ols was described via an
iodine-catalyzed tandem process. Various pyrido[2,3-d]-
pyrimidin-4-ols were rapiddly obtained from easily
available 2-amino-4-aryl-6-arylnicotinamide and benzylic
Table 1 Optimization of the reaction conditions for 2-phenylpyrido[2,3-d]pyrimidin-4-ol (2a)a
Entry
1b
2
I2/mmol
0.05
BnNH2/mmol
TBHP/mmol
Solvent
T/℃
90
Yield/%
55
2
2
2
2
2
0.05
90
62
3
2
90
0
4c
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.10
0.20
2
90
12
5
2
2
2
MeCN
H2O
90
20
6
2
90
18
7
2
2
t-BuOH
1,4-dioxane
90
15
8
2
2
90
20
9
2
2
100
110
100
100
100
100
100
100
100
78
10
11
12
13
14
15
16
17
2
2
78
1.5
2.5
3
2
70
2
80
2
80
2.5
2.5
2.5
2.5
1.5
2.5
2
75
76
90
2
85
a
Reaction conditions: the mixture of 1a (1 mmol), BnNH2, I2 and TBHP was focused under microwave irradiation at 10 W for 8 min.
b Pyridine (0.05 mmol) was added. c 30% of aqueous H2O2 was used as oxidant and 0.5 mL of solvent was added.
Chin. J. Chem. 2011, 29, 1646— 1650
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Wang et al.
FULL PAPER
Table 2 Synthesis of 5-aryl-2-phenyl-7-arylpyrido[2,3-d]pyrimidin-4-ols 2a— 2m under MWIa
Entry
1
R1
H
R2
H
Product 2
2a
Isolated yield/%
90
93
90
83
80
90
78
88
80
85
85
87
80
2
4-Br
H
2b
3
4-Cl
H
2c
4
4-CH3
4-CH3O
4-F
H
2d
5
H
2e
6
H
2f
7
2-CH3O
H
H
2g
8
4-Br
4-Br
4-Br
4-Br
4-Br
4-Br
2h
9
4-CH3
4-Cl
2i
10
11
12
13
2j
4-F
2k
4-Br
2l
4-CH3O
2m
a Reaction condition: 2-amino-4-aryl-6-arylnicotinamides 1 (1 mmol), BnNH2 (2.5 mmol), I2 (0.10 mmol) and TBHP (2 mmol), focused
microwave irradiation at 100 ℃, 8 min, 10 W.
Scheme 1 Proposed mechanism of the tandem reaction
amines under focused microwave irradiation. The reac-
tion did not involve any metal salt, excluding the residue
of a metal ion in the products.
Microwave reactions were conducted using a CEM
Focused MicrowaveTM Synthesis System (CEM Corp.,
Matthews, NC). The machine consists of a continuous
focused microwave power delivery system with operator
selectable power output from 0 to 300 W. The pressure
control system uses a load cell for an indirect measure-
ment of the reaction vessel contents. The load cell is
connected to a 10 mL vessel and senses changes in the
external deflection of the septa on top of the sealed
pressure vessel. The sensor housing incorporates a cap-
ture and release mechanism to secure the reaction in the
cavity. Pressure is programmable from 0 to 2.1×106 Pa.
The temperature control system uses a non-contact, in-
frared sensor to measure temperature. It is located below
Experimental section
IR spectra were measured for KBr discs using a Digi-
1
lab Merlin FT-IR spectrophotometer. H NMR spectra
were recorded on a Mercury plus 400 MHz spectrometer
in DMSO with TMS as an internal standard. 13C NMR
spectra were obtained at 100 MHz in DMSO with TMS
as an internal standard using a Mercury plus 400 MHz
spectrometer. HRMS was recorded on a Bruker Dalton-
ics APEXII 47e FT-ICR spectrometer.
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 1646— 1650

Molecular Iodine Promoted Synthesis of New Pyrido[2,3-d]pyrimidin-4-ols
the microwave cavity floor and measures the tempera-
ture on the bottom of the vessel. The sensor is vessel
volume independent and is used in a feedback loop with
the on-board computer to control the temperature rise
rate and control point of the vessel contents. Tempera-
ture is programmable from 25—250 ℃. All experi-
ments were performed using a stirring option whereby
the contents of the vessel are stirred by means of a ro-
tating magnetic plate located below the floor of the mi-
crowave cavity and a Teflon-coated magnetic stir bar in
the vessel.
found 410.1054.
2,7-Diphenyl-5-p-tolylpyrido[2,3-d]pyrimidin-4-ol
(2d) 1H NMR (DMSO-d6, 400 MHz) δ: 12.70 (s, 1H),
8.47—8.40 (m, 4H), 7.94 (s, 1H), 7.81—7.70 (m, 6H),
7.58 (d, J＝8.0 Hz, 2H), 7.41 (d, J＝8.0 Hz, 2H), 2.66 (s,
3H); 13C NMR (DMSO-d6, 100 MHz) δ: 161.8, 160.2,
160.1, 155.6, 153.2, 137.5, 137.3, 136.4, 132.3, 131.9,
130.4, 128.9, 128.8, 128.7, 128.1, 128.0, 127.6, 120.9,
112.2, 20.9; FT-IR (KBr) ν: 3443, 3184, 3069, 2921,
－1
2820, 1672, 1575, 1513, 1445, 1361, 1179＋, 696 cm ;
HRMS (ESI) calcd for C26H19N3O [M＋H] 390.1550,
found 390.1558.
Typical procedure for the synthesis of 5-aryl-2-
phenyl-7-arylpyrido[2,3-d]pyrimidin-4-ols 2a— 2m
5-(4-Methoxyphenyl)-2,7-diphenylpyrido[2,3-d]-
pyrimidin-4-ol (2e) 1H NMR (DMSO-d6, 400 MHz) δ:
12.50 (s, 1H), 8.35—8.26 (m, 4H), 7.81 (s, 1H), 7.65—
7.53 (m, 6H), 7.42 (d, J＝7.8 Hz, 2H), 7.25 (d, J＝7.8
Hz, 2H), 3.81 (s, 3H); 13C NMR (DMSO-d6, 100 MHz)
δ: 162.0, 160.6, 160.3, 155.9, 153.3, 139.6, 137.6, 132.4,
132.3, 130.5, 129.2, 128.8, 128.7, 128.5, 127.8, 127.7,
127.5, 120.9, 112.4, 58.9; FT-IR (KBr) ν: 3442, 3183,
3067, 2－900, 2538, 1672, 1600, 1492, 1445, 1361, 1176,
In a 10 mL glass tube were placed 2-amino-4-aryl-6-
arylnicotinamide 1 (1 mmol), benzylic amine (2.5
mmol), iodine (0.10 mmol), TBHP (2 mmol) and a
magnetic stir bar. The vessel was sealed with a septum
and placed into the microwave cavity. Microwave irra-
diation of 10 W was used, the temperature being ramped
from room temperature to 100 ℃. Once 100 ℃ was
reached, the reaction mixture was held at this tempera-
ture for 8 min. After cooling the mixture to room tem-
perature, the reaction vessel was opened and the con-
tents poured into a flask. Then ethanol was added and
the mixture was filtered and recrystallized from DMF
and ethanol.
＋
1
778 cm ; HRMS (ESI) calcd for C26H19N3O2 [M＋H]
406.1510, found 406.1521.
5-(4-Fluorophenyl)-2,7-diphenylpyrido[2,3-d]-
pyrimidin-4-ol (2f) 1H NMR (DMSO-d6, 400 MHz) δ:
12.56 (s, 1H), 8.32—8.24 (m, 4H), 7.83 (s, 1H), 7.67—
7.55 (m, 6H), 7.44 (d, J＝8.1 Hz, 2H), 7.27 (d, J＝8.1
Hz, 2H); 13C NMR (DMSO-d6, 100 MHz) δ: 163.3,
161.9, 160.9, 160.4, 160.1, 155.7, 152.1, 137.4, 135.6,
132.3, 132.0, 131.1, 131.0, 130.5, 128.9, 128.7, 128.1,
127.7, 120.9, 114.4, 114.2, 112.3; FT-IR (KBr) ν: 3447,
3198, 3－070, 2956, 1667, 1573, 1542, 1500, 1387, 1179,
2,5,7-Triphenylpyrido[2,3-d]pyrimidin-4-ol (2a)
1H NMR (DMSO-d6, 400 MHz) δ: 12.54 (s, 1H), 8.33—
8.25 (m, 4H), 7.81 (s, 1H), 7.64—7.53 (m, 7H), 7.51—
7.44 (m, 4H); 13C NMR (DMSO-d6, 100 MHz) δ: 161.8,
160.3, 160.1, 155.7, 153.1, 139.4, 137.4, 132.3, 131.9,
130.5, 128.9, 128.8, 128.6, 128.1, 127.8, 127.6, 127.4,
120.8, 112.2; FT-IR (KBr) ν: 3444, 3193, 3051, 2955,
＋
1
692 cm ; HRMS (ESI) calcd for C25H16FN3O [M＋H]
390.1315, found 390.1325.
－1
1670, 1572, 1543, 1492, 1389, 768,＋693 cm ; HRMS
5-(2-Methoxyphenyl)-2,7-diphenylpyrido[2,3-d]-
pyrimidin-4-ol (2g) 1H NMR (DMSO-d6, 400 MHz) δ:
12.51 (s, 1H), 8.36—8.27 (m, 4H), 7.82 (s, 1H), 7.66—
7.54 (m, 6H), 7.43—7.26 (m, 4H), 3.82 (s, 3H); 13C
NMR (DMSO-d6, 100 MHz) δ: 162.1, 160.4, 160.2,
155.9, 153.2, 139.5, 137.4, 132.4, 132.1, 130.5, 129.3,
128.8, 128.7, 128.5, 127.7, 127.6, 127.4, 120.9, 112.4,
57.7; FT-IR (KBr) ν: 3443, 3183, 3061, 2930, 2860,
(ESI) calcd for C25H17N3O [M＋H] 376.1400, found
376.1416.
5-(4-Bromophenyl)-2,7-diphenylpyrido[2,3-d]-
pyrimidin-4-ol (2b) 1H NMR (DMSO-d6, 400 MHz)
δ: 12.55 (s, 1H), 8.34—8.26 (m, 4H), 7.82 (s, 1H), 7.65—
7.54 (m, 6H), 7.42 (d, J＝8.1 Hz, 2H), 7.25 (d, J＝8.1
Hz, 2H); 13C NMR (DMSO-d6, 100 MHz) δ: 161.9,
160.4, 160.3, 155.8, 153.2, 139.6, 137.6, 132.4, 132.3,
130.6, 128.9, 128.8, 128.7, 128.3, 127.9, 127.8, 127.5,
120.8, 112.3; FT-IR (KBr) ν: 3446, 3183, 3061, 2955,
－1
1669, 1600, 1496, 1445, 1364, 1173,＋753 cm ; HRMS
(ESI) calcd for C26H19N3O2 [M＋H] 406.1510, found
406.1521.
－1
1670, 1572, 1543, 1492, 1389, 1176, 772 cm ; HRMS
7-(4-Bromophenyl)-2,5-diphenylpyrido[2,3-d]-
pyrimidin-4-ol (2h) 1H NMR (DMSO-d6, 400 MHz)
δ: 12.56 (s, 1H), 8.35—8.27 (m, 4H), 7.83 (s, 1H), 7.66—
7.46 (m, 10H); 13C NMR (DMSO-d6, 100 MHz) δ: 162.1,
160.6, 160.4, 155.8, 153.3, 140.3, 137.7, 132.5, 132.4,
130.5, 128.9, 128.8, 128.7, 128.5, 127.9, 127.8, 127.5,
121.0, 112.5;. FT-IR (KBr) ν: 3450, 3185, 3068, 2955,
(ESI) calcd for C25H16BrN3O [M ＋ H] ＋ 454.0560,
found 454.0569.
5-(4-Chlorophenyl)-2,7-diphenylpyrido[2,3-d]-
pyrimidin-4-ol (2c) 1H NMR (DMSO-d6, 400 MHz) δ:
12.57 (s, 1H), 8.36—8.27 (m, 4H), 7.83 (s, 1H), 7.68—
7.57 (m, 6H), 7.45 (d, J＝8.0 Hz, 2H), 7.30 (d, J＝8.0
Hz, 2H); 13C NMR (DMSO-d6, 100 MHz) δ: 162.1,
160.6, 160.4, 155.8, 153.3, 139.7, 137.6, 132.5, 132.3,
130.7, 129.2, 128.8, 128.7, 128.4, 127.9, 127.8, 127.5,
120.9, 112.5; FT-IR (KBr) ν: 3448, 3186, 3070, 2956,
－1
1670, 1573, 1543, 1500, 1389, 1178, ＋776 cm ; HRMS
(ESI) calcd for C25H16BrN3O [M＋H] 454.0560, found
454.0570.
7-(4-Bromophenyl)-2-phenyl-5-p-tolylpyrido[2,3-d]-
pyrimidin-4-ol (2i) 1H NMR (DMSO-d6, 400 MHz) δ:
12.51 (s, 1H), 8.37—8.28 (m, 4H), 7.82 (s, 1H), 7.66—
－1
1672, 1575, 1544, 1500, 1389, 1179, 776 cm ; HRMS
(ESI) calcd for C25H16ClN3O [M ＋ H] ＋ 410.1047,
Chin. J. Chem. 2011, 29, 1646— 1650
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
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Wang et al.
FULL PAPER
Font, M. Bioorg. Med. Chem. 2007, 15, 1659.
7.57 (m, 5H), 7.55 (d, J＝7.8 Hz, 2H), 7.45 (d, J＝8.1
Hz, 2H), 2.37 (s, 3H); 13C NMR (DMSO-d6, 100 MHz)
δ: 163.1, 161.6, 161.4, 156.8, 154.3, 140.7, 138.6, 133.5,
133.3, 131.7, 130.2, 129.8, 129.7, 129.4, 128.9, 128.8,
128.5, 121.9, 113.5, 22.7; FT-IR (KBr) ν: 3448, 3184,
3069, 2921, 2820, 1672, 1575, 1513, 1445, 1361, 1179,
2
Piper, J. R.; McCaleb, G. S.; Montgomery, J. A.; Kisliuk, R.
L.; Gaumont, Y.; Sirotnaks, F. M. J. Med. Chem. 1986, 29,
1080.
Robins, B. R.; Hitciiings, G. J. Am. Chem. Soc. 1958, 80,
3449.
3
4
5
－1
696 cm ; HRMS (ESI) calcd for C26H18BrN3O [M＋
Quintela, J. M.; Peinador, C.; Botana, L.; Estevez, M.;
Riguera, R. Bioorg. Med. Chem. 1997, 5, 1543.
Nam, G.; Yoon, C. M.; Kim, E.; Rhee, C. K.; Kim, J. H.;
Shin, J. H.; Kim, S. H. Bioorg. Med. Chem. Lett. 2001, 11,
611.
Zheng, G. Z.; Mao, Y.; Lee, C. H.; Patt, J. K.; Koenig, J. R.;
Perner, R. J.; Cowart, M. D.; Gfesser, G. A.; McGaraughty,
S.; Chu, K. L.; Zhu, C.; Yu, H.; Kohlhaas, K.; Alexander, K.
M.; Wismer, C. T.; Mikusa, J.; Jarvis, M. F.; Kowaluk, E.
A.; Stewart, A. O. Bioorg. Med. Chem. Lett. 2003, 13, 3041.
Connolly, C. J.; Hamby, J. M.; Schroeder, M. C.; Barvian,
M.; Lu, G. H.; Panek, R. L.; Amar, A.; Shen, C.; Kraker, A.
J.; Fry, D. W.; Klohs, W. D.; Doherty, A. M. Bioorg. Med.
Chem. Lett. 1997, 7, 2415.
H]＋ 468.0645, found 468.0657.
7-(4-Bromophenyl)-5-(4-chlorophenyl)-2-phenyl-
pyrido[2,3-d]pyrimidin-4-ol (2j) 1H NMR (DMSO-d6,
400 MHz) δ: 12.59 (s, 1H), 8.38—8.29 (m, 4H), 7.85 (s,
1H), 7.70—7.62 (m, 5H), 7.59 (d, J＝8.4 Hz, 2H), 7.49
(d, J＝8.1 Hz, 2H); 13C NMR (DMSO-d6, 100 MHz) δ:
164.1, 162.6, 162.4, 157.8, 155.3, 141.7, 139.6, 134.5,
134.3, 132.7, 131.2, 130.8, 130.7, 130.4, 129.9, 129.8,
129.5, 122.9, 114.5; FT-IR (KBr) ν: 3452, 3190, 3075,
6
7
－1
2959, 1676, 1578, 1544, 1503, 1389, 1182, 778 cm ;
HRMS (ESI) calcd for C25H15BrClN3O [M ＋ H] ＋
488.0112, found 488.0100.
7-(4-Bromophenyl)-5-(4-fluorophenyl)-2-phenyl-
pyrido[2,3-d]pyrimidin-4-ol (2k) 1H NMR (DMSO-d6,
400 MHz) δ: 12.55 (s, 1H), 8.34—8.26 (m, 4H), 7.84 (s,
1H), 7.69—7.59 (m, 5H), 7.55 (d, J＝8.0 Hz, 2H), 7.48
(d, J＝8.1 Hz, 2H); 13C NMR (DMSO-d6, 100 MHz) δ:
164.3, 162.7, 161.5, 161.0, 160.8, 156.6, 152.9, 137.9,
136.2, 133.3, 133.0, 132.1, 132.0, 131.5, 129.1, 129.0,
128.8, 128.3, 121.7, 115.4, 115.2, 113.0; FT-IR (KBr) ν:
3450, 3194, 3073, 2957, 1670, 1575, 1545, 1500, 1385,
8
9
Monge, A.; Martinez-Merino, V.; Sanmartin, C.; Fernandez,
F. J.; Ochoa, M. C.; Bellver, C. Eur. J. Med. Chem. 1989,
24, 209.
Parish, H. A. Jr.; Gilliom, R. D. J. Med. Chem. 1982, 25, 98.
10 Lakshmi Narayana, B.; Raghu Ram Rao, A.; Shanthan Rao,
P. Eur. J. Med. Chem. 2009, 44, 1369.
11 Li, J. J.; Nahra, J.; Johnson, A. R.; Bunker, A. J. Med. Chem.
2008, 51, 835.
12 Kasparec, J.; Adams, J. L.; Siskob, J.; Silva, D. J. Tetrahe-
dron Lett. 2003, 44 4567.
13 Zhang, J.-T.; Zhu, D.-P.; Yu, C.-M.; Wan, C.-F.; Wang,
Z.-Y. Org. Lett. 2010, 12, 2841.
14 Zeng, L.-Y.; Cai, C. J. Comb. Chem. 2010, 12, 35.
15 He, Z.-H.; Li, H.-R.; Li, Z.-P. J. Org. Chem. 2010, 75, 4636.
16 Mehta, S.; Larock, R. C. J. Org. Chem. 2010, 75, 1652.
17 Carmen, S.; Mikel, E.; Beatriz, M.; Lucía, C.; Elena, C.
Bioorg. Med. Chem. 2005, 13, 2031.
18 Hannah, E. B.; David, C. B.; Christopher, J. M.; Christopher,
J. H. J. Org. Chem. 2010, 75, 8674.
19 Xiao, Z. L.; Yang, M. G.; Li, P.; Carter, P. H. Org. Lett.
2009, 11, 1421.
20 Galema, S. A. Chem. Soc. Rev. 1997, 26, 233.
21 Varma, R. S. Green Chem. 1999, 1, 43.
22 Dallinger, D.; Kappe, C. O. Chem. Rev. 2007, 107, 2563.
23 Polshettiwar, V.; Varma, R. S. Chem. Soc. Rev. 2008, 37,
1546.
24 Kambe, S.; Saito, K.; Sakurai, A.; Midorikawa, H. Synthesis
1980, 366.
25 Lisa, C. W. C.; Jacobien, K. von F. D. K.; Thea, M.-K.;
Joost, W.; Thomas, S.; Johannes, B.; Adriaan, P. I. J. Med.
Chem. 2007, 50, 828.
－1
1181, 695 cm ; HRMS (ESI) calcd for C25H15BrFN3O
[M＋H]＋ 472.0383, found 472.0370.
5,7-Bis(4-bromophenyl)-2-phenylpyrido[2,3-d]-
pyrimidin-4-ol (2l) 1H NMR (DMSO-d6, 400 MHz) δ:
12.57 (s, 1H), 8.37—8.29 (m, 4H), 7.85 (s, 1H), 7.68—
7.60 (m, 5H), 7.58 (d, J＝8.0 Hz, 2H), 7.48 (d, J＝8.0
Hz, 2H); 13C NMR (DMSO-d6, 100 MHz) δ: 162.1,
161.4, 161.3, 156.3, 154.2, 139.9, 138.5, 133.4, 133.3,
131.1, 129.6, 129.2, 129.1, 129.0, 128.5, 128.3, 128.1,
121.4, 113.3; FT-IR (KBr) ν: 3454, 3188, 3067, 2957,
－1
1676, 1576, 1548, 1497, 1392, 1180, 778 cm ; HRMS
(ESI) calcd for C25H15Br2N3O [M＋H]＋ 531.9582,
found 531.9597.
7-(4-Bromophenyl)-5-(4-methoxyphenyl)-2-phenyl-
pyrido[2,3-d]pyrimidin-4-ol (2m) 1H NMR (DMSO-d6,
400 MHz) δ: 12.52 (s, 1H), 8.36—8.27 (m, 4H), 7.82 (s,
1H), 7.66—7.59 (m, 5H), 7.56 (d, J＝7.8 Hz, 2H), 7.45
(d, J＝8.1 Hz, 2H), 3.82 (s, 3H); 13C NMR (DMSO-d6,
100 MHz) δ: 162.3, 160.8, 160.5, 156.1, 153.5, 139.8,
137.8, 132.6, 132.5, 130.7, 129.4, 129.0, 128.9, 128.7,
128.0, 127.9, 127.7, 121.2, 112.6, 59.1; FT-IR (KBr) ν:
3443, 3185, 3068, 2900,－2541, 1675, 1600, 1496, 1445,
1363, 1178, 778 cm 1; HRMS (ESI) calcd for
C26H18BrN3O2 [M＋H]＋ 484.0582, found 484.0594.
26 (a) Li, Z. P.; Li, C. J. J. Am. Chem. Soc. 2004, 126, 11810.
(b) Li, Z. P.; Li, C. J. J. Am. Chem. Soc. 2005, 127, 3672.
27 Zhang, J.-T.; Wang, Z.-T.; Wang, Y.; Wan, C.-F.; Zheng,
X.-Q. Green Chem. 2009, 11, 1973.
References
1
Cordeu, L.; Cubedo, E.; Bandres, E.; Rebollo, A.; Saenz, X.;
(E1011252 Zhao, C.; Zheng, G.)
1650
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