Simple procedure for the synthesis of 5,7-diarylpyrido[2,3-d]pyrimidine derivatives catalyzed by KF-alumina

Article abstract of DOI:10.1080/00397910801997488

A simple KF/Al2O3-catalyzed reaction of 1,3-diaryl-2-propen-1-one and 2,6-diamino-4-hydroxylpyrimidine in ethyl alcohol gave aromatized 5,7-diarylpyrido[2,3-d]pyrimidine derivative by air oxidation. On the other hand, the unaromatized intermediate products were isolated under dry nitrogen successfully. A possible reaction mechanism with two pathways to lose water was proposed based on the further experimental results; one of them was confirmed by 1H NMR spectra of isolated intermediate product. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910801997488

Synthetic Communications1, 38: 1896–1908, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910801997488
Simple Procedure for the Synthesis of
5,7-Diarylpyrido[2,3-d]pyrimidine Derivatives
catalyzed by KF-Alumina
Xiang-Shan Wang1,2, Mei-Mei Zhang2, Qing Li1,
Chang-Sheng Yao1, and Shu-Jiang Tu1,2
1School of Chemistry and Chemical Engineering, Xuzhou Normal University,
Xuzhou Jiangsu, China
2Key Laboratory of Biotechnology for Medical Plant,
Xuzhou Normal University, Xuzhou Jiangsu, China
Abstract: A simple KF=Al2O3-catalyzed reaction of 1,3-diaryl-2-propen-1-one
and 2,6-diamino-4-hydroxylpyrimidine in ethyl alcohol gave aromatized 5,7-
diarylpyrido[2,3-d]pyrimidine derivative by air oxidation. On the other hand,
the unaromatized intermediate products were isolated under dry nitrogen success-
fully. A possible reaction mechanism with two pathways to lose water was pro-
posed based on the further experimental results; one of them was confirmed by
1H NMR spectra of isolated intermediate product.
Keywords: Air oxidation; KF-Al2O3; pyrido[2,3-d]pyrimidine; Synthesis
INTRODUCTION
The utility of fluoride salts as potential bases in a variety of synthetic
reactions has been recognized in recent years.[1] In particular, potassium
fluoride coated with alumina (KF-alumina) has been a versatile solid-
supported reagent developed by Ando et al. for alkylation.[2] Over the
years, the reagent has found application in a large number of organic
reactions. In our previous article,[3] we have reported the synthesis of pyr-
ido[2,3-d]pyrimidine from aldehyde, malononitrile, or cyanoacetate with
Received October 12, 2007
Address correspondence to Xiang-Shan Wang, School of Chemistry and
Chemical Engineering, Xuzhou Normal University, Xuzhou Jiangsu 221116,
P. R. China. E-mail: xswang1974@yahoo.com
1896

Synthesis of 5,7-Diarylpyrido[2,3-d ]pyrimidines
1897
6-aminouracil successfully using this reagent. Pyrido[2,3-d]pyrimidines
and their derivatives were reported to possess biological and pharmaco-
logical activities, such as antifolate activity,[4] antibacterial activity,[5]
antimicrobial activity,[6] anti-inflammatory and analgesic activity,[7] antil-
eishmanial activity,[8] anticonvulsant activity,[9] and anti-aggressive
activity.[10] These prompted us to synthesize these compounds through
another simple route. Herein we report a highly efficient method for syn-
thesis of 5,7-diarylpyrido[2,3-d]pyrimidine derivatives by the reaction of
1,3-diaryl-2-propen-1-one and 2,6-diamino-4-hydroxylpyrimidine cata-
lyzed by KF-Al2O3.
RESULTS AND DISCUSSION
When the 1,3-diaryl-2-propen-1-one (1) and 2,6-diamino-4-hydroxylpyr-
imidine (2) were treated with KF-Al2O3 in ethyl alcohol at 80 ꢀC, the desired
5,7-diarylpyrido[2,3-d]pyrimidine derivatives (3) were obtained (Scheme 1)
with high yields, which were the further aromatization products.
We began our study of the reaction shown in Scheme 1 by optimizing
the reaction conditions for preparation of 3. A summary of the optimiza-
tion experiment is provided in Table 1. The results showed that at room
temperature, no reaction took place (Table 1, Entry 1). The reaction was
first carried out in EtOH in the absence of KF=Al2O3; only trace of 3a
was observed (Table 1, entry 3). Similar reactions were then attempted
in the presence of KF=Al2O3 with 50, 100, and 150 mg. From Table 1
(entries 4, 5 and 6), we could see using of just 100 mg of KF-Al2O3 at
80 ꢀC in EtOH was sufficient to push the reaction forward. Higher
amounts of the catalyst did not improve the results to a greater extent.
In addition, MeCN and DMF were also tested as the reaction solvents.
In these cases, product 3a was formed in slightly lower yield (Table 1,
entries 7 and 8).
To demonstrate the efficiency and scope of the present method, a
variety of 1,3-diaryl-2-propen-1-ones were subjected to reaction with
2,6-diamino-4-hydroxyl pyrimidine at the same reaction conditions. As
Scheme 1. The reaction of 1,3-diaryl-2-propen-1-one and 2,6-diamino-4-hydro-
xylpyrimidine catalyzed KF-Al2O3.

1898
X.-S. Wang et al.
Table 1. Yields of product 3a at different reaction conditionsa
Entry
Catalyst amount (mg)
Temp. (ꢀC)
Solvent
Yields (%)b
1
2
3
4
5
6
7
8
100
100
0
0
50
80
80
80
80
80
90
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
0
72
trace
65
78
78
74
76
50
100
150
100
100
CH3CN
DMF
aReaction condition: 10 mL solvent, 2 mmol 1, 2 mmol 2.
bIsolated yields.
shown in Table 2, we can see the reactions proceeded smoothly to afford
the corresponding products 3 in good yields. All the products were char-
1
acterized by H NMR, IR spectra, and elemental analysis.
According to the structure of 3, a sequential reaction of the Michael
addition reaction, intramolecular nucleophilic addition, and aromatiza-
tion may take place during the formation of the product (Scheme 2).
Table 2. KF=Al2O3-catalyzed reactions of 1,3-diaryl-2-propen-1-ones and 2,6-
diamino-4-hydroxylpyrimidinea
Entry
Ar
Ar0
Products
Time (h)
Yields (%)b
1
2
3
4
5
6
7
8
9
C6H5
4-CH3OC6H4
C6H5
4-ClC6H4
4-ClC6H4
4-ClC6H4
C6H5
4-FC6H4
4-ClC6H4
2-ClC6H4
C6H5
4-BrC6H4
C6H5
3a
3b
3c
3d
3e
3f
10
9
8
79
81
86
81
80
79
84
85
82
83
84
80
2-Thiophenyl
3-ClC6H4
C6H5
4-ClC6H4
3-CH3C6H4
C6H5
2-ClC6H4
C6H5
3-NO2C6H4
4-ClC6H4
4-CH3OC6H4
8
10
12
9
9
9
8
8
10
3g
3h
3i
10
11
12
3j
3k
3l
aReaction condition: 10 mL EtOH, 2 mmol 1, 2 mmol 2, 100 mg KF-Al2O3,
80ꢀC.
bIsolated yields.

Synthesis of 5,7-Diarylpyrido[2,3-d ]pyrimidines
1899
Scheme 2. The possible reaction mechanism.
From Scheme 2, two possible pathways were proposed to lose the
water, giving the two unaromatized intermediate products I or II. It
was reported[11] that the dihydropyrido[2,3-d]pyrimidine derivatives were
unstable to their corresponding aromatization products by air oxidation
automatically. To prevent the air oxidation and obtain the unaromatized
intermediates, we tested the same reaction under dry nitrogen (Scheme 3).
To our delight, the desired intermediate II was isolated, which was con-
1
firmed by H NMR spectra. The spectrum of 4a was shown in Fig. 1.
Obviously, it was typical AM system for protons on the positions of 5
and 6, not ABX system, so the structure of the intermediate was II rather
than I. The results of unaromatized 5,7-diarylpyrido[2,3-d]pyrimidine
derivatives are summarized in Table 3.
If the unaromatized intermediate product 4f was treated in EtOH at
80 ꢀC for 10 h (Scheme 4), it gave the corresponding 3f in 72% yield.
This result indicated that the air oxidation took place in the formation
of products 3.
Scheme 3. The reaction of 1,3-diaryl-2-propen-1-one and 2,6-diamino-4-hydro-
xylpyrimidine under N2.

1900
X.-S. Wang et al.
Figure 1. 1H NMR of compound 4a (400 MHz).
CONCLUSION
In conclusion, we found a convenient method for the synthesis of 5,7-
diarylpyrido[2,3-d]pyrimidine derivatives by the reaction of 1,3-diaryl-2-
propen-1-one and 2,6-diamino-4-hydroxylpyrimidine catalyzed by
KF-Al2O3. This method has the advantage of an easy workup, milder
Table 3. KF-Al2O3-catalyzed reactions of 1,3-diaryl-2-propen-1-one and 2,6-dia-
mino-4-hydroxylpyrimidine under nitrogena
Entry
Ar
Ar0
Products Time (min) Yields (%)b
1
2
3
4
5
6
7
8
9
C6H5
3,4-(CH3O)2C6H3 C6H5
4-ClC6H4
4a
4b
4c
4d
4e
4f
40
45
50
40
60
50
60
40
50
82
81
83
86
80
73
82
88
72
2-Thiophenyl
3-NO2C6H4
3-NO2C6H4
4-CH3C6H4
C6H5
4-ClC6H4
C6H5
4-ClC6H4
C6H5
C6H5
4g
4h
4i
4-ClC6H4
4-CH3OC6H4
C6H5
C6H5
aReaction condition: 10 mL EtOH, 2 mmol 1, 2 mmol 2, 100 mg KF-Al2O3, 80 ꢀC.
bIsolated yields.

Synthesis of 5,7-Diarylpyrido[2,3-d ]pyrimidines
1901
Scheme 4. The subsequent aromatization in air.
reaction conditions, and good yields in the synthesis of these potential
active compounds.
EXPERIMENTAL
Melting points were determined in open capillaries and are uncorrected.
IR spectra were recorded on a Tensor 27 spectrometer in KBr. 1H NMR
spectra were obtained for solution in DMSO-d6 with Me4Si as internal
standard using an Inova-400 spectrometer. Elemental analyses were
carried out using a Perkin-Elmer 2400 II analyzer.
The 2,6-diamino-4-hydroxylpyrimidine was purchased from Aldrich
Chemical Company, Inc. The starting materials of 1,3-diaryl-2-propen-
1-one were prepared as references reported.[12]
General Procedure for the 2-Amino-5,7-diarylpyrido[2,3-d]
pyrimidine-4(3H)-one 3
A dry 100-mL flask was charged with 1,3-diaryl-2-propen-1-one 1
(2 mmol), 2,6-diamino-4-hydroxylpyrimidine 2 (2 mmol), KF=Al2O3
(100 mg), and EtOH (10 mL). The mixture was stirred at 80 ꢀC for 8–12 h.
Then after being cooled to room temperature, the solid material was
filtered off. The crude product was purified by recrystallization from
DMF and water, followed by keeping at 80ꢀC for 2 h in a vacuum to give 3.
Data
2-Amino-7-(4-methoxylphenyl)-5-phenylpyrido[2,3-d]
pyrimidine-4(3H)-one 3a
This compound was obtained as yellow powder, mp >300 ꢀC; IR (KBr):
nmax 3329, 3154, 2929, 1647, 1610, 1509, 1455, 1301, 1249, 1207, 1123,

1902
X.-S. Wang et al.
1108, 1032, 852, 832, 799, 766, 745; 1H NMR (DMSO-d6): d 3.81
(s, 3H, CH3O), 6.69 (b, 2H, NH2), 7.04 (d, J ¼ 8.8 Hz, 2H, ArH),
7.32 (s, 1H, ArH), 7.38 (s, 5H, ArH), 8.16 (d, J ¼ 8.8 Hz, 2H, ArH),
10.91 (b, 1H, ArH). Anal. calcd. for C20H16N4O2: C, 69.76; H, 4.68;
N, 16.27. Found: C, 69.87; H, 4.50; N, 16.33.
2-Amino-7-phenyl-5-thiophenylpyrido[2,3-d]pyrimidine-4(3H)-one 3b
This compound was obtained as yellow powder, mp >300 ꢀC; IR (KBr):
nmax 3305, 3255, 3144, 3071, 2835, 1696, 1672, 1659, 1578, 1547, 1441,
1409, 1329, 1287, 1253, 1218, 1102, 889, 851, 777, 690; 1H NMR
(DMSO-d6): d 6.72 (b, 2H, NH2), 7.17–7.13 (m, 1H, ArH), 7.35–7.51
(m, 6H, ArH), 7.69 (d, J ¼ 4.8 Hz, 1H, ArH), 8.16–8.18 (m, 2H, ArH),
11.08 (b, 1H, NH). Anal. calcd. for C17H12N4OS: C, 63.73; H, 3.78; N,
17.49. Found: C, 63.90; H, 3.68; N, 17.55.
2-Amino-7-(4-chlorophenyl)-5-(3-chlorophenyl)pyrido[2,3-d]
pyrimidine-4(3H)-one 3c
This compound was obtained as yellow powder, mp >300 ꢀC; IR (KBr):
nmax 3088(b), 1680, 1573, 1549, 1475, 1408, 1357, 1284, 1233, 1162, 1121,
1091, 1011, 974, 877, 834, 820, 789, 710, 696; 1H NMR (DMSO-d6): d 6.74
(b, 2H, NH2), 7.34–7.47 (m, 5H, ArH), 7.56 (d, J ¼ 8.4 Hz, 2H, ArH), 8.24
(d, J ¼ 8.8 Hz, 2H, ArH), 11.02 (b, 1H, NH). Anal. calcd. for C19H12Cl2N4O:
C, 59.55; H, 3.16; N, 14.62. Found: C, 59.68; H, 3.09; N, 14.78.
2-Amino-7-(4-chlorophenyl)-5-phenylpyrido[2,3-d]
pyrimidine-4(3H)-one 3d
This compound was obtained as yellow powder, mp >300 ꢀC; IR (KBr):
nmax 3468, 3306, 3221, 3067, 1663, 1597, 1549, 1524, 1458, 1385, 1254,
1239, 1181, 1092, 1043, 1012, 858, 833, 825, 788, 760, 742, 696; 1H
NMR (DMSO-d6): d 6.72 (b, 2H, NH2), 7.42 (s, 5H, ArH), 7.56 (s, 1H,
ArH), 7.34–7.47 (m, 5H, ArH), 7.60 (d, J ¼ 8.4 Hz, 2H, ArH), 8.24 (d,
J ¼ 8.4 Hz, 2H, ArH), 10.98 (b, 1H, NH). Anal. calcd. for C19H13ClN4O:
C, 65.43; H, 3.76; N, 16.06. Found: C, 65.50; H, 3.59; N, 16.13.
2-Amino-5,7-di(4-chlorophenyl)pyrido[2,3-d]pyrimidine-4(3H)-one 3e
This compound was obtained as yellow powder, mp >300 ꢀC; IR (KBr):
nmax 3315, 3158, 1641, 1575, 1520, 1487, 1455, 1414, 1393, 1357, 1274,

Synthesis of 5,7-Diarylpyrido[2,3-d ]pyrimidines
1903
1
1091, 1013, 831; H NMR (DMSO-d6): d 6.73 (b, 2H, NH2), 7.41–7.46
(m, 5H, ArH), 7.56 (d, J ¼ 8.4 Hz, 2H, ArH), 8.23 (d, J ¼ 8.4 Hz, 2H,
ArH), 11.00 (b, 1H, NH). Anal. calcd. for C19H12Cl2N4O: C, 59.55; H,
3.16; N, 14.62. Found: C, 59.76; H, 3.10; N, 14.71.
2-Amino-5-(4-methylphenyl)-7-phenylpyrido[2,3-d]
pyrimidine-4(3H)-one 3f
This compound was obtained as yellow powder, mp >300 ꢀC; IR (KBr):
nmax 3149(b), 3031, 2918, 2856, 1683, 1654, 1625, 1575, 1541, 1524,
1413, 1361, 1280, 1253, 1156, 1115, 812; 1H NMR (DMSO-d6): d 2.38 (s,
3H, CH3), 6.68 (b, 2H, NH2), 7.20 (d, J ¼ 8.0 Hz, 2H, ArH), 7.30
(d, J ¼ 8.0 Hz, 2H, ArH), 7.35 (s, 1H, ArH), 7.49–7.51 (m, 3H, ArH),
8.16–8.18 (m, 2H, ArH), 10.93 (b, 1H, NH). Anal. calcd. for C20H16N4O:
C, 73.15; H, 4.91; N, 17.06. Found: C, 73.28; H, 4.77; N, 17.25.
2-Amino-7-(4-fluorophenyl)-5-phenylpyrido[2,3-d]
pyrimidine-4(3H)-one 3g
This compound was obtained as yellow powder, mp >300 ꢀC; IR (KBr):
nmax 3315, 3141, 3081, 1692, 1673, 1657, 1605, 1575, 1547, 1512, 1492,
1415, 1357, 1285, 1234, 1157, 985, 845, 772, 691; H NMR (DMSO-
1
d6): d 6.70 (b, 2H, NH2), 7.30–7.39 (m, 8H, ArH), 8.24–8.32 (m, 2H,
ArH), 10.94 (b, 1H, NH). Anal. calcd. for C19H13FN4O: C, 68.67; H,
3.94; N, 16.86. Found: C, 68.55; H, 3.89; N, 16.70.
2-Amino-7-(4-chlorophenyl)-5-(2-chlorophenyl)pyrido[2,3-d]
pyrimidine-4(3H)-one 3h
This compound was obtained as yellow powder, mp >300 ꢀC; IR (KBr):
n
max 3305(b), 3066, 1645, 1592, 1573, 1547, 1518, 1477, 1412, 1361, 1306,
1254, 1092, 1056, 1032, 1012, 834, 825, 744; 1H NMR (DMSO-d6): d 6.24
(b, 2H, NH2), 7.32–7.50 (m, 5H, ArH), 7.56 (d, J ¼ 8.4 Hz, 2H, ArH),
8.23 (d, J ¼ 8.4 Hz, 2H, ArH), 10.99 (b, 1H, NH). Anal. calcd. for
C19H12Cl2N4O: C, 59.55; H, 3.16; N, 14.62. Found: C, 59.58; H, 3.23;
N, 14.69.
2-Amino-7-(2-chlorophenyl)-5-phenylpyrido[2,3-d]
pyrimidine-4(3H)-one 3i
This compound was obtained as yellow powder, mp >300 ꢀC;IR (KBr):
nmax 3320, 3255, 3156, 1693, 1673, 1607, 1569, 1547, 1492, 1479, 1410,
1
1344, 1251, 1235, 1162, 881, 796, 778, 699; H NMR (DMSO-d6): d 6.70

1904
X.-S. Wang et al.
(b, 2H, NH2), 7.40 (s, 5H, ArH), 7.45 (s, 1H, ArH), 7.51–7.55 (m, 2H,
ArH), 8.16 (d, J ¼ 7.2 Hz, 1H, ArH), 8.26 (d, J ¼ 1.6 Hz, 1H, ArH),
10.97 (b, 1H, NH). Anal. calcd. for C19H13ClN4O: C, 65.43; H, 3.76;
N, 16.06. Found: C, 65.55; H, 3.60; N, 16.23.
2-Amino-5-(3-nitrophenyl)-7-phenylpyrido[2,3-d]
pyrimidine-4(3H)-one 3j
This compound was obtained as yellow powder, mp >300 ꢀC; IR (KBr):
n
max 3393, 3161(b), 1678, 1650, 1607, 1581, 1547, 1527, 1434, 1404, 1347,
1
1310, 1243, 1173, 1098, 778, 740, 697, 688; H NMR (DMSO-d6): d 6.75
(b, 2H, NH2), 7.51 (s, 4H, ArH), 7.68–7.72 (m, 1H, ArH), 7.89 (d,
J ¼ 8.4 Hz, 1H, ArH), 8.21–8.28 (m, 4H, ArH), 11.03 (b, 1H, NH). Anal.
calcd. for C19H13N5O3: C, 63.51; H, 3.65; N, 19.49. Found: C, 63.66;
H, 3.59; N, 19.28.
2-Amino-7-(4-bromophenyl)-5-(4-chlorophenyl)pyrido[2,3-d]
pyrimidine-4(3H)-one 3k
This compound was obtained as yellow powder, mp >300 ꢀC; IR (KBr):
nmax 3294, 3120, 1682, 1624, 1595, 1572, 1541, 1520, 1485, 1411, 1358,
1276, 1255, 1093, 1072, 1011, 959, 856, 838, 815, 758; 1H NMR
(DMSO-d6): d 6.60 (b, 2H, NH2), 7.36 (d, J ¼ 8.0 Hz, 2H, ArH), 7.42
(s, 1H, ArH), 7.56–7.60 (m, 4H, ArH), 8.22 (d, J ¼ 8.4 Hz, 2H, ArH),
11.02 (b, 1H, NH). Anal. calcd. for C19H12BrClN4O: C, 53.36; H, 2.83;
N, 13.10. Found: C, 53.30; H, 2.69; N, 13.13.
2-Amino-5-(4-methoxylphenyl)-7-phenylpyrido[2,3-d]
pyrimidine-4(3H)-one 3l
This compound was obtained as yellow powder, mp >300 ꢀC; IR (KBr): nmax
3288, 3113, 1683, 1653, 1625, 1608, 1578, 1541, 1511, 1456, 1419, 1403, 1362,
1279, 1248, 1178, 1161, 1114, 1033, 861, 830, 775; 1H NMR (DMSO-d6): d
3.81 (s, 3H, CH3O), 6.66 (s, 2H, NH2), 6.95 (d, J ¼ 8.8 Hz, 2H, ArH), 7.37
(d, J ¼ 8.8 Hz, 2H, ArH), 7.47–7.54 (m, 3H, ArH), 8.17–8.19 (m, 2H,
ArH), 10.95 (b, 1H, NH). Anal. calcd. for C20H16N4O2: C, 69.76; H, 4.68;
N, 16.27. Found: C, 69.92; H, 4.54; N, 16.20.
General Procedure for the 2-Amino-5,7-diaryl-5,8-dihydropyrido
[2,3-d]pyrimidine-4(3H)-one 4
A dry 100-mL flask was charged with 1,3-diaryl- 2-propen-1-one 1
(2 mmol), 2,6-diamino-4-hydroxylpyrimidine 2 (2 mmol), KF=Al2O3

Synthesis of 5,7-Diarylpyrido[2,3-d ]pyrimidines
1905
(100 mg), and EtOH (10 mL) under dry nitrogen, The mixture was stirred
at 80 ꢀC for 40–60 min. Then after being cooled to room temperature, the
solid material was filtered off and the crude product was purified by
recrystallization from 95% EtOH to give 4.
Data
2-Amino-7-(4-chlorophenyl)-5-phenyl-5,8-dihydropyrido[2,3-d]
pyrimidine-4(3H)-one 4a
This compound was obtained as yellow powder, mp 230–232 ꢀC; IR
(KBr): nmax 3330, 2927, 1639, 1527, 1465, 1406, 1371, 1256, 1236, 1203,
1179, 1159, 1071, 1043, 1024, 1010, 822, 769, 700; H NMR (DMSO-
1
=
d6): d 4.58 (d, J ¼ 5.2 Hz, 1H, CH), 5.09 (d, J ¼ 5.2 Hz, 1H, CH ),
6.16 (b, 2H, NH2), 7.10–7.14 (m, 1H, ArH), 7.22–7.25 (m, 4H, ArH),
7.40 (d, J ¼ 8.4 Hz, 2H, ArH), 7.52 (d, J ¼ 8.4 Hz, 2H, ArH), 8.40
(b, 1H, NH), 10.18 (b, 1H, NH). Anal. calcd. for C19H15ClN4O: C,
65.05; H, 4.31; N, 15.97. Found: C, 64.90; H, 4.51; N, 15.89.
2-Amino-5-(3,4-dimethoxylphenyl)-7-phenyl-5,8-dihydropyrido
[2,3-d]pyrimidine-4(3H)-one 4b
This compound was obtained as yellow powder, mp 235–236 ꢀC; IR
(KBr): nmax 3566, 3356, 3141, 1716, 1653, 1558, 1541, 1517,1457, 1418,
1316, 1259, 1180, 1138, 1026, 793, 735, 700; 1H NMR (DMSO-d6):
d 3.69 (s, 3H, CH3O), 3.70 (s, 3H, CH3O), 4.52 (d, J ¼ 5.2 Hz, 1H,
=
CH), 5.08 (d, J ¼ 5.2 Hz, 1H, CH ), 6.14 (b, 2H, NH2), 6.74
(d, J ¼ 8.4 Hz, 1H, ArH), 6.84 (d, J ¼ 8.4 Hz, 1H, ArH), 6.91 (s, 1H,
ArH), 7.31–7.37 (m, 3H, ArH), 7.49–7.51 (m, 2H, ArH), 8.28 (b, 1H,
NH), 10.16 (b, 1H, NH). Anal. calcd. for C21H20N4O3: C, 67.01;
H, 5.36; N, 14.88. Found: C, 66.87; H, 5.54; N, 14.80.
2-Amino-7-(4-chlorophenyl)-5-(2-thiophenyl)-5,8-dihydropyrido
[2,3-d]pyrimidine-4(3H)-one 4c
This compound was obtained as yellow powder, mp 253–255 ꢀC; IR
(KBr): nmax 3629, 3474, 3224, 3085, 2929, 1665, 1602, 1482, 1385, 1319,
1257, 1231, 1219, 1186, 1172, 1126, 1105, 1092, 1046, 1013, 860, 849,
827, 792, 772, 695, 669; 1H NMR (DMSO-d6): d 4.88 (d, J ¼ 5.2
0
=
Hz, 1H, CH), 5.17 (dd, J ¼ 5.2 Hz, J ¼ 1.6 Hz, 1H, CH ), 6.20 (b,
2H, NH2), 6.87–6.90 (m, 2H, ArH), 7.23 (dd, J ¼ 4.8 Hz, J0 ¼ 1.2 Hz,

1906
X.-S. Wang et al.
1H, ArH), 7.43 (d, J ¼ 8.8 Hz, 2H, ArH), 7.54 (d, J ¼ 8.8 Hz, 2H, ArH),
8.56 (b, 1H, NH), 10.25 (b, 1H, NH). Anal. calcd. for C17H13ClN4OS: C,
57.22; H, 3.67; N, 15.70. Found: C, 57.10; H, 3.68; N, 15.92.
2-Amino-5-(3-nitrophenyl)-7-phenyl-5,8-dihydropyrido[2,3-d]
pyrimidine-4(3H)-one 4d
This compound was obtained as yellow powder, mp >300 ꢀC; IR (KBr):
nmax 3327, 2927, 2729, 1645, 1526, 1466, 1406, 1349, 1257, 1236, 1209,
1187, 1161, 1096, 1044, 942, 918, 896, 852, 807, 772, 738, 701; 1H
NMR (DMSO-d6): d 4.78 (d, J ¼ 5.2 Hz, 1H, CH), 5.08 (d, J ¼ 5.2 Hz,
=
1H, CH ), 6.26 (b, 2H, NH2), 7.34–7.38 (m, 3H, ArH), 7.51–7.53
(m, 2H, ArH), 7.56–7.60 (m, 1H, ArH), 7.75 (d, J ¼ 7.2 Hz, 1H, ArH),
8.03 (dd, J ¼ 8.4 Hz, J0 ¼ 1.2 Hz, 1H, ArH), 8.07 (s, 1H, ArH), 8.54 (b,
1H, NH), 10.24 (b, 1H, NH). Anal. calcd. for C19H15N5O3: C, 63.15;
H, 4.18; N, 19.38. Found: C, 63.27; H, 4.22; N, 19.10.
2-Amino-7-(4-chlorophenyl)-5-(3-nitrophenyl)-5,8-dihydropyrido
[2,3-d]pyrimidine-4(3H)-one 4e
This compound was obtained as yellow powder, mp >300 ꢀC; IR (KBr):
nmax 3216, 2927, 1653, 1599, 1525, 1471, 1412, 1389, 1348, 1256, 1180,
1094, 1049, 1013, 840, 806, 740, 678. 1H NMR (DMSO-d6): d 4.77
=
(d, J ¼ 5.2 Hz, 1H, CH), 5.11 (d, J ¼ 5.2 Hz, 1H, CH ), 6.26 (b, 2H,
NH2), 7.42 (d, J ¼ 8.4 Hz, 2H, ArH), 7.53 (d, J ¼ 8.4 Hz, 2H, ArH),
7.55–7.60 (m, 1H, ArH), 7.74 (d, J ¼ 7.6 Hz, 1H, ArH), 8.01–8.06
(m, 2H, ArH), 8.63 (b, 1H, NH), 10.27 (b, 1H, NH). Anal. calcd. for
C19H14ClN5O3: C, 57.66; H, 3.57; N, 17.69. Found: C, 57.60; H, 3.68;
N, 17.54.
2-Amino-5-(4-methylphenyl)-7-phenyl-5,8-dihydropyrido[2,3-d]
pyrimidine-4(3H)-one 4f
This compound was obtained as yellow powder, mp 223–224ꢀC; IR
(KBr): nmax 3451, 3386, 3269, 3059, 2922, 1638, 1536, 1462, 1372, 1257,
1233, 1178, 1091, 1043, 1025, 813, 794, 776, 766, 699; 1H NMR
(400 MHz, DMSO-d6, d, ppm): 2.22 (s, 3H, CH3), 4.52 (d, J ¼ 5.2 Hz,
=
1H, CH), 5.06 (d, J ¼ 5.2 Hz, 1H, CH ), 6.18 (b, 2H, NH2), 7.03
(d, J ¼ 8.0 Hz, 2H, ArH), 7.12 (d, J ¼ 8.0 Hz, 2H, ArH), 7.30–7.35
(m, 3H, ArH), 7.47–7.50 (m, 2H, ArH), 8.29 (b, 1H, NH), 10.19 (b,
1H, NH). Anal. calcd. for C20H18N4O: C, 72.71; H, 5.49; N, 16.96.
Found: C, 72.65; H, 5.58; N, 16.87.

Synthesis of 5,7-Diarylpyrido[2,3-d ]pyrimidines
1907
2-Amino-5,7-diphenyl-5,8-dihydropyrido[2,3-d]pyrimidine-4(3H)-one 4g
This compound was obtained as yellow powder, mp 243–245 ꢀC; IR
(KBr): nmax 3468, 3376, 3278, 3063, 2877, 1639, 1596, 1529, 1491, 1465,
1396, 1370, 1259, 1235, 1202, 1180, 1158, 1135, 1094, 1064, 1030, 877,
1
798, 771, 756, 699; H NMR (DMSO-d6): d 4.58 (d, J ¼ 5.2 Hz, 1H,
=
CH), 5.06 (d, J ¼ 5.2 Hz, 1H, CH ), 6.21 (b, 2H, NH2), 7.10–7.13
(m, 1H, ArH), 7.24–7.39 (m, 6H, ArH), 7.48–7.50 (m, 3H, ArH), 8.34
(b, 1H, NH), 10.24 (b, 1H, NH). Anal. calcd. for C19H16N4O: C, 72.13;
H, 5.10; N, 17.71. Found: C, 72.28; H, 5.40; N, 17.62.
2-Amino-5-(4-chlorophenyl)-7-phenyl-5,8-dihydropyrido[2,3-d]
pyrimidine-4(3H)-one 4h
This compound was obtained as yellow powder, mp 228–230ꢀC; IR
(KBr): nmax 3325, 2927, 1640, 1524, 1488, 1461, 1410, 1372, 1283, 1256,
1204, 1179, 1159, 1089, 1015, 936, 828, 795, 770, 699; 1H NMR
(DMSO-d6): d 4.60 (d, J ¼ 5.2 Hz, 1H, CH), 5.04 (dd, J ¼ 5.2 Hz,
0
=
J ¼ 1.6 Hz, 1H, CH ), 6.19 (b, 2H, NH2), 7.25–7.37 (m, 7H, ArH),
7.49 (d, J ¼ 8.0 Hz, 2H, ArH), 8.38 (b, 1H, NH), 10.21 (b, 1H, NH).
Anal. calcd. for C19H15ClN4O: C, 65.05; H, 4.31; N, 15.97. Found: C,
64.88; H, 4.30; N, 16.09.
2-Amino-5-(4-methoxylphenyl)-7-phenyl-5,8-dihydropyrido[2,3-d]
pyrimidine-4(3H)-one 4i
This compound was obtained as yellow powder, mp 185–186 ꢀC; IR
(KBr): nmax 3329, 3154, 2929, 2834, 1648, 1509, 1456, 1301, 1250, 1207,
1174, 1108, 1032, 852, 832, 799, 767, 746, 696; H NMR (DMSO-d6):
1
d 3.69 (s, 3H, CH3O), 4.53 (d, J ¼ 5.2 Hz, 1H, CH), 5.05 (dd, J ¼ 5.2 Hz,
0
=
J ¼ 1.6 Hz, 1H, CH ), 6.18 (b, 2H, NH2), 6.81 (d, J ¼ 8.4 Hz, 2H,
ArH), 7.16 (d, J ¼ 8.4 Hz, 2H, ArH), 7.32–7.37 (m, 3H, ArH), 7.48–
7.53 (m, 2H, ArH), 8.28 (b, 1H, NH), 10.24 (b, 1H, NH). Anal. calcd.
for C20H18N4O2: C, 69.35; H, 5.24; N, 16.17. Found: C, 69.20; H, 5.38;
N, 16.22.
ACKNOWLEDGMENTS
We are grateful to the Natural Science Foundation (06AXL010) of
Xuzhou Normal University for financial support.

1908
X.-S. Wang et al.
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